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The Official Publication of the National Ataxia Foundation Volume 34, Number 3 Fall 2006 Sporadic Ataxia

Presented by Susan L. Perlman, MD Susan L. Perlman, MD is a Clinical Professor of Neurology and Director of the Ataxia Center/Neurogenetics Clinic at the David Geffen School of Medicine at UCLA. She is the principle investigator for a pilot study of the National Ataxia Database and Registry (funded by NAF) and is a site director for the Friedreich’s Ataxia Clinical Outcome Measures Center Study (P.I. Dr. David Lynch at Children’s Hospital of Philadelphia). The UCLA Ataxia Center is a multi-disciplinary evaluation and treatment program for patients with inherited and acquired cerebellar disorders, whose activities have been partially supported by the Mariette Monnier bequest. The following was presented at the 2006 NAF Annual Membership Meeting in Boston, MA.

What is Sporadic Ataxia? The definition of research focus in the sporadic ataxias. That is a sporadic from the dictionary is “having no good thing about these conventions, you all pattern or order, appearing singularly, isolated can get together and network and the doctors or unique.” When referring to patients with as well and hopefully some great things will sporadic ataxia, there is no history in the family come out of this. and the gene tests have been negative. There- We often use sporadic and non-genetic fore, the doctor tells the patient it is sporadic. equivalently but is anything really non-genetic? At UCLA the sporadic ataxias are not so isolat- There is a quote from an article written a ed or unique in that over 60% of our patients couple of years ago indicating that our genes in our database have non-genetic ataxia. determine how tall we are, what our eye color What questions concern patients with is, what our personalities are going to be like ... sporadic ataxia? What do I have? Is there a probably influence everything, including our cause that can be found? Are my children going susceptibility to cerebellar ataxia, even if we to have this? Can it be cured and will it get don’t have one of the known ataxia genes. worse? Is research being done? These are Looking at neurologic diseases for genetic questions that we have answers for as they susceptibility, there are two groups. The first relate to the genetic ataxias but I think the group is the one gene one disease group where answers to research in sporadic ataxias are the SCA’s/FA ataxia belong. Usually there is a lagging behind. This is a concern I share with family history that gives you some clue you are Dr. Schamahmann. I had a long talk with him about the need to really “ramp up” our Continued on page 3 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:46 AM Page 2

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Please direct correspondence to: Generations Staff: National Ataxia Foundation Lisa Marie McLevis, Lori Shogren, 2600 Fernbrook Lane, Suite 119 Becky Kowalkowski, Julie Braun and Mike Parent Minneapolis, MN 55447-4752 Donna Gruetzmacher ...... Advisor Phone: (763) 553-0020 FAX: (763) 553-0167 Design, Production and Printing...... Leader Printing Internet: www.ataxia.org Madison, SD E-mail: [email protected] Generations is published by the National Ataxia Foundation, Inc., Minneapolis, MN. Copyright 2006 by the National Ataxia Foundation, Inc. All rights reserved. We ask that other publications contact us for permission to reprint any article from Generations.

Disclaimer The NAF does not endorse products, services, or manufacturers. Those that are mentioned in Generations are included only for your information. The National Ataxia Foundation assumes no liability whatsoever for the use or contents of any product or service mentioned in the newsletter.

Table of Contents Annual Membership Meeting Articles Sporadic Ataxia...... 1 Stock Talk ...... 10 Review of What We Have Learned ...... 15 GoodSearch for a Great Cause...... 12 2007 Meeting: “The Bridge to Hope”...... 24 So Many Ways to Give...... 19 Research Summaries Tell Your Story in Generations ...... 22 Young Ataxia Hero...... 23 Investigatin Gluten-Dependent Autoimmunity as a Possible Cause Generations Word Find ...... 28 of Sporadic Ataxia ...... 6 Featured Board Member of the NAF: BOAT1, an AXH Domain Protein, Earl McLaughlin ...... 26 Suppresses the Cytotoxicity of Ataxin-1 ...... 11 A Leader Remembered: Kay Bell ...... 27 Deranged Calcium Signaling NAF’s New Web Site...... 29 in SCA3 Neurons...... 13 Boosting Food Intake...... 30 A Novel Ataxia in a Pedigree From the Desk of the Executive Director ...... 33 from the Philippines ...... 13 Letter to the Editor ...... 35 Genetic Programs Regulation Cell Young Adult Group on MSN...... 46 Fate Decisions in the Rhombic Lip, a Birthsite of Neurons Affected in Ataxia...... 18 Membership Topics Development of a Mouse Model of NAF Merchandise...... 32 Spinocerebellar Ataxia with Neuropathy ...... 20 Chapter and Support Group News ...... 36 Mouse Model for X-Linked NAF Chapters and Support Groups...... 41 Congenital Ataxia ...... 21 Ambassador Listing...... 43 Calendar of Events...... 45 Memorials and In Your Honor...... 47 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:46 AM Page 3

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Sporadic Ataxia people were studied to find that gene. How are Continued from page 1 we going to find a new ataxia gene with some- one who has two living family members with dealing with a primary genetic disease. ataxia? Drs. Schmahmann and Ranum have On the other side we have an interesting ideas to speed up gene research. However, 95% group of susceptibility genes where one or of patients without family history will probably more genes acting together with other factors have non-genetic or sporadic ataxia and will in the environment and your lifestyle. This have negative gene tests no matter how many means you could develop neurologic problems gene tests we do. On the other hand, 5% of like Multiple Sclerosis, Parkinson disease and people without a family history actually have possibly some of the ataxias like the ones we genetic ataxia. call sporadic and possibly MSA. Why is there In Friedreich’s ataxia and other recessive no family history? Dr. Pulst reviewed this. You ataxias there will be a family history because may think you have sporadic ataxia if you don’t they are recessive. It requires two genes to have anyone else in your family that has had come together, one from each side of the ataxia, perhaps you didn’t ask or the doctor family. It may also be the first generation. didn’t explore that. Maybe the information is Mitochondrial syndromes, because of their lost. Maybe the gene that is in your family is unusual inheritance, may not have any prior hidden, it “pops up and down,” and it skips history and will appear to be sporadic. There generations. There are actually molecular are diseases that look like MSA, with Parkinson genetic mechanisms that explain the type of symptoms, and sleep disturbances. We see genes that do that. It is possible that you do not those coming together and think MSA. There have enough history and you could carry an are some genetic disorders that can look like ataxia gene. SCA 3/MJD but more often than not that On the other hand, maybe it is non-genetic. picture is non-genetic. Typical scenario: a patient has ataxia for five Does this person have MSA? This is one of years, the doctor had already sent gene testing the big questions when I am seeing someone and it came back normal, now what can you with sporadic ataxia for the first time. This is a do? We have 17 ataxia gene tests that are avail- very important question because in MSA there able (most of them available through Athena are many more things to manage systematically Diagnostics) and three tests for Hereditary FSP. than “regular” ataxia and it tends to get worse Even when people with familial ataxia, come on a fast time course. Therefore you really need up negative on all of the gene tests, there will to keep up with it. There are study groups for probably be other gene tests that come out MSA. I think, in the past year, the combined within the next six months to a year that will groups had about six articles that were pub- describe their ataxia. lished from the research that they are doing; I had a very interesting conversation with natural history research, observational research, Dr. Ranum and Dr. Schmahmann about and they are also doing some basic research into people with familial ataxia. Maybe we go back a protein that can build up in the cells of people three generations and we find 12 people who with MSA and it could be part of the problem had it but there are only two still living, how and it might be a target for treatment. They can we do genetic research on them with only have made some progress and they are working two people available? We saw Dr. Ranum’s together in a very good collaboration. work with the Lincoln pedigree where hundreds of people were seen and dozens of Continued on page 4 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:46 AM Page 4

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Sporadic Ataxia like a cross, and shaped like a hot cross bun. Continued from page 3 This could be an early indicator of someone with cerebellar ataxia that will probably evolve MSA starts like ataxia in about 20% of the into MSA. I will do test scans to see if they cases. In 8% of cases it starts like Parkinson would be an early indicator before the full disease and evolves into MSA. Usually it will syndrome developed. As Dr. Schmahmann follow all three components: ataxia, Parkinson- shared with me, the simplest thing your doctor ism and the autonomic instability. How can can do is take your blood pressure standing up you sort it out for someone you are seeing for and sitting down. If there is a significant change the first time with ataxia, in the right age and you are feeling dizzy every time you stand group (usually someone about 40 or 45)? Is this up, this could be an early indicator of MSA. going to turn into MSA or is it going to stay Dr. Harding classified the non-genetic ataxias cerebellar or cerebellar syndrome. Twenty-five into three basic categories: Type A with percent of patients with sporadic cerebellar associated dementia, Type B with associated ataxia will go on to develop MSA, usually tremor and Type C which looked like what we within five years, especially if they are over the used to call OPCA. In Type A there are age of 50. Therefore, when I see somebody notable memory problems which are less com- over the age of 50 with pure cerebellar sporadic monly seen in the genetic ataxias. There are a ataxia there is a 25% chance that person will number of conditions that fall into that start to look like MSA. category. There is Combined Cerebral Cortical Erectile dysfunction can precede the ataxia by Atrophy where you get ataxia and memory five to 10 years. Sleep disturbance can also problems, Wimples disease, which is an precede the onset of ataxia by a number of interesting infectious disease and prion diseases. years. Once the ataxia or the Parkinsonism There are people with sporadic cerebellar ataxia begins, significant motor disability is rarely where tremor is a big issue. I think many of seen by the third year. If I have someone with these individuals have recently been found to pure cerebellar syndrome, with no family have Fragile X associated tremor ataxia history and they make it to the third year still syndrome which is really a genetic syndrome on their feet it is probably not MSA. I feel but because of its unusual inheritance wasn’t comfortable counseling them and saying it will known as such until research was done in the not be turning into MSA. There are diagnostic last couple of years. Type C is the larger group studies which help differentiate MSA from the in the non-genetic ataxias and many people still regular spinocerebellar ataxias. If you see some- carry a diagnosis of OPCA. Part of that group body with dementia, paralyzed eye movements will develop MSA or other Parkinsonism or other types of involuntary movements, syndromes, and ataxia. besides ataxia and tremor, it is usually not There are treatable causes of non-genetic MSA. Those are things that are not commonly ataxia or these causes can be identified and seen. However, they are seen in the other explained. People can be reassured you have a ataxias, especially the inherited ones. disease that you acquired in your environment On MRI scans we may see changes in the that caused your ataxia. We can’t cure it but white areas or black areas. There is something you don’t have to worry about passing it along called the “hot cross buns” side. If you have to your kids. Even if there is some infectious OPCA or certain other cerebellar syndromes disease or some trauma that is now found to the pons gets smaller. You can see something in be causing your ataxia, to know that is the middle of the pons, something that looks important information for your family. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:46 AM Page 5

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We know that there are infectious causes or Treatment goals, treatment of known causes, immune system reactions to infection; we whether it is dietary, replacement therapies, know that injuries and hypothermia can devel- intoxication therapies: you improve perfor- op ataxias as years go by. There are metabolic mance with symptom specific drugs or rehabil- causes like vitamin deficiency, vitamin B12 and itation with training. Preventive bystander E deficiencies, thyroid disease can target effects: use it or lose it, means if you are living a the cerebellum and cause ataxia. Certain quality life. Prevent serious complications: medication prescribed for heart disease, chemo falling, choking, injuries, breathing problems, therapy drugs, epilepsy drugs can target the infections, depression. The ataxia may not kill cerebellum and cause cerebellar atrophy and you but these things can. We need to slow dis- ataxia. There are environmental toxins some ease progression and we need to learn more are common like alcohol and some are very about the role of antioxidants. We need to rare and some we may not even know we are learn more about neuro-protective drugs and being exposed to. gene and stem cell therapy for people with There are treatable causes involving the non-genetic ataxias. immune system. There is a lot of research The diagnostic approach is to determine if it being published now about hidden cancers that is pure cerebellar or does it involve other parts put out immune chemicals that target the cere- of the brain. You should do imaging, electro bellum. There are other antibodies produced diagnostics, and make sure you have a detailed that are not related to cancers and the one we family history and a detailed environmental hear about most is antigliadin associated with history. Consider genetic testing. Many articles sensitivity to gluten, (protein in wheat). There have been published looking at large popula- seems to be genetic evidence that this can be a tions of people with ataxia. Every ataxia center cause of ataxia, neuropathy and other neuro- has at least one of these articles, and the one I logical systems and may respond to treatment am looking at is from Dr. Jen’s group at with a gluten-free diet. UCLA. It talks about 38 patients with slowly Dr. Schmahmann is going to use anti- progressive pure cerebellar ataxia with onset immune therapy. We also use some of it at after the age of 40, primary sporadic ataxia. UCLA. If we find a bad antibody we will They screened for genes 1, 2, 3, 6, 8, 14, fragile attempt to treat it. We may get a suspicion that X, and calcium channel problems. Thirty there is an antibody involved if the person has percent of these people, with no known family another autoimmune disease not known to history, were positive for one of those genes. cause ataxia. Sometimes autoimmune diseases Eight had SCA 6, one had SCA 1, one had go hand in hand with other antibodies. It seems SCA 3 and one had SCA 8. In this particular to progress more rapidly than you would population she didn’t find any of the other expect a regular ataxia to progress especially ataxias but they have been reported in other when the immune system is involved. Many groups. It may be worthwhile to do some people seem to be progressing faster than the genetic screening if you don’t have a family doctor is comfortable with. You may want to history. try steroids. It could be a knee-jerk reaction The non-genetic ataxias are currently the from the neurologist when they think there most challenging area of research in cerebellar is an inflammation or an immune problem disease, the area most deserving of heightened going on. If you respond to the steroids it may effort and we need to be looking for suscepti- lead to other treatments including giving bility genes, environmental triggers, and specific medication lifestyle factors and age related influences. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 6

Page 6 Generations Fall 2006 Investigating Gluten-Dependent Autoimmunity as a Possible Cause of Sporadic Ataxia

Enrico Tongiorgi, PhD University of Trieste The following is a research summary of a grant funded by NAF for fiscal year 2005.

1. Summary of the specific aims symptoms like migraine, depression, increased In a considerable proportion of patients who anxiety, central and peripheral neuropathies suffer from sporadic cerebellar ataxia, a symp- and epilepsy. However, the link between spo- tom of malfunction of the cerebellum, the radic forms of ataxia and gluten sensitivity has balance centre in our brain, the cause of only recently been recognised. It is becoming the disease is not known. Strikingly, up to 40% increasingly clear that in a significant propor- of patients with ataxia of unknown cause have tion of individuals (10-40%) with neurological sensitivity to gluten. Gluten is found in cereals dysfunction of unknown aetiology (the such as wheat, oat, barley and rye (but not in commonest being ataxia and/or neuropathy) corn or rice) and is composed of proteins there is evidence of gluten sensitivity even in ingested with a normal diet. Gluten sensitivity absence of gastrointestinal disfunctions. is a very common condition (1% population Accordingly, it has been shown that removal of worldwide) and produces a variety of distur- gluten-containing products from the diet of bances within the digestive apparatus, from patients with gluten sensitivity and ataxia very mild to severe ones. While in the majority results in improvement or stabilisation of their of people these disturbances are so mild that ataxia. This is an important achievement since, remain unnoticed, in some individuals such it shows that treatment with a gluten-free diet sensitivity manifests with a severe inflamma- is a simple therapeutic option which might tion of the intestine, and is called celiac disease become available also for patients with sporadic (CD). CD is caused by an autoimmune reac- ataxia if only they could be correctly diagnosed as tion, which means that the disturbances are having a gluten-dependent autoimmune disorder. caused by production of antibodies reacting We and others have hypothesized that with one or more components of the human patients with gluten sensitivity and ataxia may body (self-antigens). In the case of CD, the have circulating antibodies in their blood able principal self-antigen is a protein called trans- to react with brain regions controlling the bal- glutaminase-2 (TGase2). In addition, there is ance. Like almost all patients with CD, patients production of antibodies against proteins that with gluten sensitivity and ataxia may also have are components of gluten, such as gliadin antibodies against gluten and the self-antigen (wheat), avenin (oat), ordein (barley) or secalin transglutaminase-2 (TGase2). On this basis, we (rye), which act as trigger of the disease. submitted to NAF a project to investigate the It was long time known that patients role of anti-TGAase2 antibodies and other with celiac disease often have neurological anti-brain autoantibodies as a possible cause Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 7

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of sporadic ataxia. We were interested in chromosome, the phage produces a coat which answering two principal questions: displays, as an additional protein, that human 1) Are anti-TGAase2 antibodies from patients antibody hence this technology is called “anti- with celiac disease, able to cause ataxia? body phage display.” Since the library contains 2) Are other anti-brain antibodies from the entire repertoire of antibodies of a patient, patients with gluten-ataxia or celiac disease able it clearly represents an unselected antibody to cause ataxia? mixture reacting against every possible self- and More in detail, during the proposed project non-self antigen. Ideally, a good phage display we pursued the following two aims: antibody library should closely match the mix- Aim 1) production of phage display antibody ture of antibodies present in the blood. Once libraries from a patient with gluten-ataxia and obtained a good library, the phage antibodies isolation of anti-TGAse2 and anti-brain reactive can be selected on target substrates similarly to autoantibodies; what we have seen for the first approach. Aim 2) assessment of the effects of passive However, the great power of the phage display transfer of purified phage autoantibodies in vivo technology is that each single phage bears only (creation of different animal models of gluten one human antibody and it can be replicated separately from the others in unlimited ataxia). amounts and then tested separately. Purified 2. Methodology preparations of antibodies, all identical among To isolate autoantibodies there are two main each other, constitute a mono-clonal antibody, approaches, both exploiting the principle that while a mixture of different antibodies repre- antibodies bind selectively to their target. In the sent a poly-clonal antibody. first, antibodies are harvested from a patient’s 3. Results blood sample and then antibodies that react with a given organ (the brain, for instance) are Results Aim 1. Production and analysis of isolated through a series of purification steps phage display antibody libraries. using as binding substrate a protein extract from Two IgA phage display libraries from a the target organ. However, this method pro- patient with CD and ataxia (Patient A) were vides only limited amounts of purified already available at the beginning of the project anti-bodies and it allows only to isolate pools of [3]. The first was made from peripheral blood antibodies reacting against several self-antigens. lymphocytes (PBL) while the other was pre- The other approach takes advantage of the fact pared starting from lymphocytes extracted from that antibodies are proteins that are produced an intestinal biopsy (IBL) of small intestine from the blood cells lymphocytes and therefore (duodenum), a region which is particularly it is possible to isolate from these cells the affected in patients with CD. The libraries were genetic information coding for each single tested for the presence of phage antibodies antibody. By cloning the genetic information of reacting with brain regions involved in motor the antibodies of a given patient into phases it is control. This test was done by immunohisto- possible to obtain a so-called phage display chemistry on rat brain sections, a procedure antibody library. Phases are inoffensive small involving the incubation of antibodies on tissue viruses that grow only in bacteria. They are sections followed by revelation of the bound composed of a short DNA chromosome sur- antibodies by a colorimetric reaction. rounded by a coat made of a small number of The two libraries of the patient A were tested proteins. When the genetic information encod- ing one antibody is inserted into the phage Continued on page 8 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 8

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Investigating Gluten-Dependent Autoimmunity... library from patient B reached a diversity of Continued from page 7 one million different clones while the IBL library reached a diversity of 200,000. Both for the presence of anti-brain IgAs in compari- libraries were of the IgG class, only. son with the patient’s serum (Fig. 1). The serum IgAs of patient A labeled neurons in the Results Aim 1. Selection of anti-brain anti- cerebellum, cortex, hippocampus, thalamus, bodies from phage display antibody libraries. colliculi (not shown) and brainstem (Fig. 1C). To isolate phages expressing antibodies Both the PBL and the IBL phage display against the central nervous system, the PBL or libraries labeled the same brain regions that IBL libraries of patients A and B were selected were also recognized by the patient serum by repetitive panning on homogenates of whole although the labeling was less intense (Fig. 1A, rat brain lysate (100μg/ml) or purified human 2B). These results demonstrated that the Tgase-2 (10μg/ml) in Maxisorb immunotubes. libraries reproduce the original IgA antibodies Unbound phage antibodies were eluted with repertoire of patient A and confirmed the pres- three washings. Phases bound to immunotubes ence of IgAs antibodies against brain antigens. have been eluted by incubation with bacteria The presence of anti-brain antibodies in the DH5αF’ at 37°C. After a second round of two libraries indicated the possibility to carry selection, single clones of infected bacteria have out the purification procedure using rat brain been dispensed into individual wells of a 96- protein extracts as a binding substrate. well plate and grown at 37°C to the OD600=0.5. M13K07 helper phage at a multiplicity of infec- tion of 20:1 have been added to each well and incubated at 37°C for 45 minutes. Half of the supernatant of each well after overnight rescue have been used directly for the characterization Fig. 1: Immunohistochemistry of IgAs serum, by ELISA on rat brain lysate (100μg/ml) or PBL and IBL phage antibody libraries from TGase-2 (10μg/ml). After two rounds of selec- patient A on rat brainstem. The serum IgAs of tion, we have extracted the DNA from the patient A gave a positive staining on neurons of vari- ous rat brain areas including Purkinje cells and deep clones found positive and the genes encoding cerebellar nuclei of cerebellum, cortex, hippocampus, the antibodies were analyzed though a proce- thalamus, collicoli and brainstem. The staining was dure called DNA finger printing consisting in a particularly strong on the nuclei of neurons. Similar digestion of the DNA with specific enzymes pattern was obtained using the PBL IgAs library (A) and the IBL IgAs library (B) and serum IgAs (C). producing a series of bands whose number and length is characteristic for each antibody gene. Since the type of antibodies that are most Only differet antibodies were used for further involved in autoimmune diseases are those of studies. In Fig. 2 one such finger printing anal- the IgG class, we have also constructed two ysis is shown. Here, two antibodies from the new IgGs phage display antibody libraries from PBL library of patient A were found to be iden- a patient with gluten-ataxia but without overt tical (compare lanes 1 with 2, and 4 with 5). gastrointestinal manifestations (Patient B). The Finally, the specificity of each positive clone genetic information encoding IgG antibodies was re-tested in ELISA on TGase-2 or on rat was extracted from peripheral blood (PBL) or brain lysate and on the negative control bovine intestinal biopsy lymphocytes (IBL) from this serum albumin (BSA) as show in Fig. 3 for the patient. Production of the libraries has followed clone 2L.1. previously developed methods [1]. The PBL We have isolated in total 20 different Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 9

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antibodies (10 IgAs and 10 IgGs, see Table 1) from the phage libraries obtained from the patient with CD and ataxia (8 anti- brain + 2 anti-Tgase2 IgAs, Patient A) and the patient with gluten ataxia but no gastrointestinal symptoms (8 anti-brain + 2 anti-Tgase2 IgGs, Patient B).

Table 1. Summary of the isolated phage antibodies. Anti-brain Anti-TGAse2 Total/#clones antibodies antibodies analyzed Patient A, PBL library 2 0 1 IgA / 376 Patient A, IBL library 6 2 8 IgAs / 282 Patient B, PBL library 2 0 2 IgG / 334 Patient B, IBL library 6 2 8 IgGs / 268+184 TOTAL 16 4 20 / 1444 Fig. 2: Characterization of anti-brain scFvs from the PBL Results Aim 2. Injection of anti-TGase2 IgA phage antibodies of Patient A by fingerprinting. in mice. Two monoclonal IgA scFv anti- To investigate if anti-TGase2 antibodies have a role in causing bodies have been selected from the whole PBL library of Patient A on ataxia, we injected two purified single chain anti-TGase2 anti- rat brain lysate. To characterize bodies (class 1 and class 2 from Patient A) in the lateral ventricle them, they have been digested of C57BL/6 male mice and we tested the effect on equilibrium. with two restriction enzymes. In Mice were trained during 3-5 days to stay in equilibrium for lane 1 and 2 it is shown the diges- tion with the HaeIII enzyme of 2 min on a rotarod (Ugo Basile, Italy) at 9 rpm speed, and then 2L.1 and 2L.2 scFvs respectively. were implanted with a cannula and finally tested on the rotarod In lane 4 and 5 it is reported the 1h, 3h, 6h and 24h after the antibody injection (latency to fall digestion with BstnI enzyme of was recorded). When mice were treated with class 1 or class 2 the same scFvs. The two IgA scFvs antibodies, they manifested a severe ataxia at 3h and 6h after resulted identical. Lane 3=100bp molecular weight. injection (Fig. 4, page 10) while injection of pep1, a control antibody, had no effect (Fig. 4, page 10). To confirm that the injection cannula had hit the lateral ventricle and that no inflammatory processes were in course, brain were extracted and frontal sections were stained with hematoxylin and eosin dyes. Data from mice in which the cannula was misplaced were not used. 4. Conclusions Fig. 3: Comparison between For an autoimmune disorder to be defined as such, five the reactivity of 2L.1 scFv on requirements need to be met: 1) the presence of circulating rat brain and BSA. The mono- autoantibodies directed to the affected organ, 2) the presence of clonal 2L.1 IgA scFv antibody selected from the PBL library of antibody deposits within the affected organ; 3) the positive Patient A has been tested in response of the patient to immuno-suppressive treatments; 4) ELISA on rat brain lysate (grey possibility to transfer passively the pathology in animals through columns 100μg/ml) and on BSA infusion of antibodies or lymphocytes; 5) induction of the (white columns 10μg/ml). Signals pathology in humans or animals through administration of high have been normalized on the reactivity value of the secondary doses of self-antigens. antibody on rat brain lysate and BSA respectively. Continued on page 10 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 10

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Investigating Gluten-Dependent Autoimmunity... cause ataxia from a patient’s blood sample will Continued from page 9 provide a simple but powerful tool to identify which patients with sporadic ataxia have this Before the present study, gluten-ataxia met autoimmune disease allowing clinicians to only three of these criteria: 1) most, but not all, undertake the appropriate treatment at earlier patients gluten sensitivity and ataxia have anti- stages of the disease. brain antibodies; 2) in 50% of gluten ataxia patients there is evidence of intrathecal anti- 5. Literature cited body production; 3) immuno-suppressive 1. Sblattero, D. and A. Bradbury, Exploiting therapy or a strict gluten-free diet can improve recombination in single bacteria to make large the neurological symptoms in some patients. phage antibody libraries. Nat Biotechnol, 2000. This study provides evidence that gluten ataxia 18(1): p. 75-80. meets requirement 4). We demonstrated that 2. Sblattero, D. and A. Bradbury, A defini- sera from gluten ataxia patients can provoke tive set of oligonucleotide primers for amplify- transient ataxia in mice after intraventricular ing human V regions. Immunotechnology, 1998. injection and that the motor deficits observed 3(4): p. 271-8. in mice reflect the clinical findings observed in 3. Marzari, R., et al., Molecular dissection of humans. To determine if other antibodies also the tissue transglutaminase autoantibody have a causative role in ataxia, the purified response in celiac disease. J Immunol, 2001. phase antibodies will be injected in mice and 166(6): p. 4170-6. their effects will be assessed. This part of the 4. Marks, J.D., et al., By-passing immuniza- project will be terminated in future, if funds tion. Human antibodies from V-gene libraries will be available. displayed on phage. J Mol Biol, 1991. 222(3): In perspective, identifying the antibodies that p. 581-97. 5. Kang, A.S., et al., Linkage of recognition and replication functions by assembling combi- natorial antibody Fab libraries along phage surfaces. Proc Natl Acad Sci USA, 1991. 88(10): p. 4363-6. ❖

Fig. 4: Motor coordination test on the rotarod. Stock Talk Mice treated with monoclonal antibodies received Directly donating appreciated stock to the three trials at 9 rpm before the intraventricular injec- National Ataxia Foundation has significant tion (Pre in.), and 1h, 3h, 6h, 24h after antibodies tax advantages. There is no capital gains injection. The means of the duration of balance or tax and you also receive a tax deduction on latency to fall (maximum trial duration=120 sec) of the value of the stock gifted. the three trials was recorded. Mice treated with There are a number of supporters of NAF anti-tTGase monoclonal antibody class 1 and class 2 who have seen first-hand the tax advan- exhibit significant difficulty in maintaining balance tages of directly donating appreciated stock. on the rotarod 3h and 6h after injection compared To take full advantage of the tax laws, to the performance before intraventricular injection. please consult your tax accountant or finan- Mice treated with negative control monoclonal cial advisor before you make a gift of stock. antibody pep 1 showed no decline in performance. Please call us at (763) 553-0020 if you Error bars represent SE. n= number of animals would like more information. *** P< 0,005 (Wilcoxon test) ** P< 0,01 (Wilcoxon test) * P< 0,05 (Wilcoxon test) Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 11

Fall 2006 Generations Page 11 BOAT1, an AXH Domain Protein, Suppresses the Cytotoxicity of Ataxin-1 Chih-Cheng Tsai, PhD UMDNJ-Robert Wood Johnson Medical School The following is a research summary of a grant funded by NAF for fiscal year 2005.

To date, nine polyglutamine diseases have participate in transcriptional repression. been identified, including six forms of Our characterization of BOAT1 led us to the spinocerebellar ataxias (SCA1, 2, 3/MJD, 6, 7, further discovery that BOAT1 also interacts and 17), Huntington’s disease, Kennedy’s dis- with ATXN1. This surprising finding, coupled ease, and Haw River Syndrome/DRPLA. My with the known interactions between ATXN1 research focuses on SCA1, which is known to or BOAT1 and SMRT, indicate that these be caused by the glutamine-repeat expanded three proteins engage in complex protein- form of the protein ataxin-1 (ATXN1). SCA1 protein interactions. As a result, a triple protein patients display ataxia, progressive motor complex forms; we predicted, moreover, that deterioration and loss of Purkinje cells in the the properties of each protein would be influ- cerebellum. So far, the molecular events that enced by its other two binding partners. To test contribute to the degeneration of Purkinje cells whether this is the case, we decided to examine in SCA1 patients remain unclear. My recent how BOAT1 and SMRT are expressed in work with ATXN1 indicated that its toxic Purkinje cells and whether their expression is effects may, in part, involve a related protein, affected by mutant ATXN1. Since a mouse which we called Brother of ataxin-1 (BOAT1). model for SCA1 has been established (in these We first identified BOAT1 from the human mice, mutant ATXN1 is specifically expressed genome, because this uncharacterized protein in Purkinje cells), we decided to use these shares similar protein sequences with ATXN1. SCA1 mice for our studies. We were particu- We additionally found a protein very similar to larly keen on examining the expression of BOAT1 in the mouse genome. Comparing the BOAT1 and SMRT in the Purkinje cells of sequences of human and mouse ATXN1 and very young SCA1 mice, particularly prior to BOAT1, we found that one particular region, the stage when nuclear inclusions (the hallmark called the AXH domain, is most conserved of many polyglutamine diseases) and ataxia among these four vertebrate proteins. Our behavior can be detected. We reasoned that, if subsequent studies revealed that the AXH BOAT1 or SMRT expression is altered by domain is required for both ATXN1 and mutant ATXN1at a very early stage, either or BOAT1 to interact with an important nuclear both proteins will likely be involved in the factor called SMRT (Silencing Mediator of SCA1-mediated degeneration of Purkinje cells. retinoid and thyroid hormone receptors). We carried our work out through immuno- Because the functions of SMRT are closely staining experiments, using high quality anti- associated with transcriptional repression bodies that we developed for ATXN1, SMRT, (meaning that SMRT helps to turn many genes and BOAT1, respectively. These antibodies off), the physical association of ATXN1 and allow us to see exactly how each protein is BOAT1 with SMRT therefore raises the possibility that both ATXN1 and BOAT1 also Continued on page 12 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 12

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BOAT1, an AXH Domain Protein... early stage. Continued from page 11 We are currently trying to determine the mechanism that mutant ATXN1 uses to shut expressed in Purkinje cells. Each of these three down the expression of BOAT1. At the same antibodies was used to immunostain frozen time, we are also in the process of developing brain sections derived from wild-type and mouse lines that are born with reduced level of SCA1 mice that were only three weeks old. At BOAT1 in their Purkinje cells. If the outcome this age, SCA1 mice show no signs of nuclear that results from lowering the expression level inclusions and ataxia. For our control experi- of BOAT1 in Purkinje cells is similar to that ment, we used Calbindin antibody, because it found for SCA1 mice, such a result would specifically labels Purkinje cells in the cere- indicate that BOAT1 may play a critical role in bellum. As shown in the accompanying Fig. A, preventing Purkinje cells from undergoing our co-immunostaining experiments for degeneration. If this is indeed the case, blocking ATXN1, SMRT, or BOAT1 and Calbindin the deleterious effects of mutant ATXN1 on revealed that both SMRT and BOAT1, like BOAT1 may provide us with strategies for ATXN1 and Calbindin, are expressed in the treating SCA1 patients. These experiments are Purkinje cells of normal mice, although the ongoing at the moment. expression level of SMRT is lower. When we We would like to mention that it would not examined the expression levels of these proteins have been possible for us to carry out and to in the age-matched SCA1 mice (see Fig. B), continue our research without the support we BOAT1, but not SMRT and the control have received from the NAF. We hope that our Calbindin, appears to disappear from virtually ongoing research into SCA1 and other all Purkinje cells. This disappearance of neurodegenerative disease proteins (such as BOAT1 is particularly striking because it takes Haw River Syndrome/DRPLA) will help place prior to the development of nuclear nurture new concepts and methods to treat inclusions and ataixa. This result tells us that these devastating neurodegenerative diseases in the biochemical damage that mutant ATXN1 the future. causes in Purkinje cells in fact begins at a very Note: As a result of the support from NAF, the following paper has been published: Mizutani, A., Rajan, H., Wang, L., Vig, PJS, Alaynick, WA, Thaler, JP, Tsai, C.-C. Boat, an AXH domain protein, suppresses the cytotoxicity of mutant atax- in-1. EMBO Journal 24, 3339-51 (2005). ❖

GoodSearch for Fig. A & B: BOAT1 expression is reduced in the Purkinje cells of SCA1 mice at the early stage. a Great Cause Frozen brain sections, prepared from three-week-old By choosing www.GoodSearch.com as wild-type (FVB/N) mice (A) or from age-matched your search engine, a donation will be SCA1 mice (B), were co-immunostained with made to the National Ataxia Foundation Calbindin antibody along with ATXN1, SMRT, with each search you do. Surf the net and or BOAT1 antibodies. The Purkinje cell layer is generate funds to support the important abbreviated as PCL. Note that Calbindin is a work of the Foundation. marker for Purkinje cells, which was used as a control. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 13

Fall 2006 Generations Page 13 Deranged Calcium Signaling in SCA3 Neurons Ilya Bezprozvanny, PhD University of Texas Southwestern Medical Center at Dallas The following is a research summary of a grant funded by NAF for fiscal year 2005.

During one year of support of the above signaling may be a cause of neuronal death in referenced NAF grant we focused on analysis of SCA3 neurons. To test this idea we now connections between calcium signaling and perform experiments with genetic mouse degeneration of SCA3 neurons. This project is model of SCA3 containing mutated human based on our discovery of association between SCA3 gene with 84 CAG expansion. We hope mutated ataxin-3 and type 1 inositol 1, 4, to demonstrate that Ca2+ signaling blockers will 5-trisphosphate receptor (InsP3R1), which is prevent or slowdown degeneration of neurons an intracellular calcium (Ca2+) release channel. in SCA3 mouse model. These studies are In biochemical experiments we demonstrated supported by renewed grant from National that mutant ataxin-3 binds to InsP3R1. In Ataxia Foundation. In addition, the grant was functional experiments we demonstrated that submitted to National Institutes of Health to mutant ataxin-3 makes InsP3R1 more active. provide further support for these experiments. Importantly, wild type ataxin-3 (without CAG I am truly thankful to the National Ataxia expansion) does not bind to InsP3R1 and does Foundation for continuous support of our not activate it. Obtained results provided strong research program on causes and potential treat- support to our hypothesis that excessive Ca2+ ments of SCA3. ❖ A Novel Ataxia in a Pedigree from the Philippines Stefan M. Pulst, MD Cedars-Sinai Medicine Center The following is a research summary of a grant funded by NAF for fiscal year 2005.

It is with great please that I submit the follow- coordination problems. We are hopeful that ing report to the National Ataxia Foundation as these findings may lead to new ways of treating a final report regarding the grant “A Novel SCA diseases. Ataxia in a Pedigree from the Philippines.” For This type of gene has never been linked to the first time, we have linked mutations in a nerve cell death. Its discovery resulted from a gene that regulates how potassium enters cells search for the gene that causes spinocerebellar to a neurodegenerative disease and to another disorder that causes mental retardation and Continued on page 14 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 14

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A Novel Ataxia... normal and close too late. This reduced the Continued from page 13 rate at which the neurons could fire. Researchers have long known that potassium ataxia in a Filipino family. This disorder typi- channels are important for neuronal function. cally appears in adulthood and causes loss of Mutations in other potassium channel genes neurons in the brain’s cerebellum, resulting in have been linked to problems such as epilepsy, progressive loss of coordination. We were able cardiac arrhythmias, and periodic muscle paral- to trace the disease in this family to mutation in ysis. One type of potassium channel defect has a gene called KCNC3. The gene codes for one also been found in a disorder called episodic of the proteins that form potassium ions into ataxia type 1 that causes brief episodes of ataxia the cell. We were also able to discover a without neurodegeneration. However, potassi- different KCNC3 mutation in a previously um channel mutations have never before been identified French family with a disease called linked to neurodegenerative disease or mental spinocerebellar ataxia type 13, which causes retardation. The findings were surprising childhood-onset ataxia, cerebel- because mice lacking the lar degeneration and mild KCNC3 gene have only mild mental retardation. The new findings behavioral changes. The KCNC3 gene codes for a “ type of potassium channel that suggest that It is not yet clear exactly how normally opens and closes very spinocerebellar the potassium channel muta- quickly. This type of channel is tions cause neurodegeneration. particularly important in “fast- ataxia ... might One theory is that the muta- bursting neurons” that fire be treatable with tions might increase the hundreds of times per second in amount of calcium that can the brain. They are like building drugs that alter enter cells, causing them to die blocks and are found extensively the activity of because of over overstimula- in the nervous system. Among potassium channels. tion. The altered potassium other places, neurons are found channels might prevent neu- in the brain’s substantia nigra, rons from coping with damage where they aid in motor control, and in the from reactive molecules called ”free radicals that are produced during hippocampus, where they play a role in learn- ing. Previous studies have found abnormalities metabolism. The mutations also might cause in the number of potassium channels in subtle developmental defects that reduce the Parkinson’s, Alzheimer’s and Huntington’s long-term survival of neurons. diseases. Together with the new study, these The new findings suggest that spinocerebellar findings suggest that potassium channel ataxia and other neurodegenerative diseases abnormalities may contribute to a wide variety might be treatable with drugs that alter the of neurodegenerative disease. activity of potassium channels. To maximize Through cell culture experiments, we have the benefits and reduce side effects, researchers learned that the KCNC3 mutations in the will need to find drugs that are specific for this Filipino and French families affect the potassi- type of channel. um channel very differently. The mutation We now plan to use cell culture and animal found in the Filipino family completely models to learn exactly how the mutations prevented the potassium channel from func- cause neurodegeneration. These studies may tioning. The mutation from the French family lead to improved treatments for a number of caused potassium channels to open earlier than diseases. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 15

Fall 2006 Generations Page 15 Review of What We Have L e a r ne d Presented by John W. Day, MD, PhD John W. Day, MD, PhD, is Professor of Neurology at the University of Minnesota and Research Medical Liaison of the National Ataxia Foundation. Dr. Day received his MD from the University of Minnesota and subsequently received a PhD in Neuroscience from the Albert Einstein College of Medicine. He trained in Neurology at the University of California, San Francisco and has been involved in the diagnosis and care of ataxia patients for 20 years. Dr. Day is Director of the Paul and Sheila Wellstone Muscular Dystrophy Center at the University of Minnesota where he has active ataxia and neuromuscular clinics. He also cares for pediatric ataxia and neuromuscular patients at the Gillette Pediatric Specialty Healthcare Clinic in St. Paul. Dr. Day has collaborated for many years with Dr. Laura Ranum and Dr. Lawrence Schut, with whom he has worked to identify and characterize SCA 5 and SCA 8 as well as other forms of ataxia. Traditionally at NAF’s Annual Membership Meeting, someone does a quick review of what the meeting’s speakers have said about their area of study. The following is Dr. John Day’s summary, as presented.

Let’s begin with Dr. Schmahmann, the local Dr. O’Hearn helped us understand aspects of guru on ataxia, who revealed to us not only degeneration and another theme that came up some inner disease in terms of the autonomy of repeatedly at the conference was the idea of the cerebellum but he also dealt with some different complements to ataxia in terms of the novel treatments. Some very common sense disease process. We have normal nerve cell aspects of controlling symptoms and opened up degeneration but there are probably some the idea of other things going on besides developmental, metabolic or energy produc- movement problems. In ataxia we usually think tion aspects to the degenerations. There are of it being aspects of problems dealing with probably some aspects of physiology where just motor control. It is not to say it isn’t a large the cells aren’t functioning properly. There are part of the disease but what it shows that we a number of different things and the more we not only have problems with movements but in understand it the more targets we have for addition to controlling motor function, we are treatment. I think that a number of the sessions also having problems with coordination of helped to understand that. thought and emotion. We are finding out that It is great to see Dr. Runko here for a the cerebellum is involved in a number of number of reasons. One of which is it is always different functions in addition to controlling good to see young people involved and our arms, legs, speech and eyes. It is also Friedreich’s ataxia is showing up in fruit flies. involved in how to coordinate, in a comparable The genetics of fruit flies are so intricately way, some of our emotions and some of our understood that it creates a powerful tool to thoughts. Therefore coordination of thought, figure out exactly what is going on electrically. coordination of motion, and coordination of emotion are all a part of this. Continued on page 16 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 16

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Review of What We Have Learned abnormal structure is leading to abnormal func- Continued from page 15 tion. We have a normal cycle of tuning the cerebellum and it is constantly clicking along in I am a strong advocate of Dr. Runko’s approach order to fine tune the coordination of motion, to understand what is going on in FA by identi- emotion, and thoughts. If the “wiring is off,” fying what is going on in the fruit fly. that is part of the underlining problem with Dr. Jen added another element in terms of ataxia. It can be a problem in the cerebellum. It what I call a physiological complement of can be a problem of the nerve cells going to the ataxia. The disease she was talking about was cerebellum or it can be a problem of outflow of not necessarily a disease of degeneration of the the cerebellum. In all ways he was able to give cerebellum as she was talking about the episod- us a sense of what is going on. ic ataxias. That gave us some new insight on Dr. Ranum showed us a new disease, hope- what may be going on in this altering function, fully, one that is going to put ataxia “on the a theme that came up at the end of Dr. Pulst’s map.” I think that we all hope that someday we talk when he started talking about aspects of will not have to explain to everyone, all the nerve cell function, electrical signaling of time, what ataxia is. In these studies of SCA 5 nerves themselves is altered and that leads to you also see the importance of not only creativ- some of the aspects of ataxia. ity but of incredible persistence to track down Dr. Pulst introduced us to a number of things the cause of this disease. It has opened up a new in his role as the Research Director for NAF. idea on how these cells are damaged. The struc- He did an outstanding job of showing where tural abnormality is within the cell. Each indi- the research money goes and the breakdown of vidual cell has its own internal skeleton and it is the grants funded, seed money for established that internal skeleton that is abnormal in SCA investigators, young investigator and post-doc 5. This leads to the damage of the individual awards and how to keep it all going. He didn’t cells of the cerebellum. Dr. Schut’s role in that have enough time to tell us about SCA 13 was interesting in a number of ways. Not only which is a new disease he discovered recently because the overall straightforward presentation that is beginning to emerge. In ataxia we have of the disease but because of his role in this degeneration of nerve cells, abnormal develop- organization and in ataxia for so many years. ment of nerve cells, and we have abnormal I really enjoyed Dr. Friedman. He exempli- function of nerve cells. A lot of these aspects are fied the humility one must have in “the front interrelated. You can start with abnormal func- lines” of seeing patients on a daily basis. We just tion such as a SCA 13 with abnormal potassium have to realize that we can’t know everything. channels which can lead to degeneration. You These diseases are complex as we learned in the can start with abnormal development which is talk by Dr. Schmahmann and how he was now suggested in some of the developmental talking about some of the other non-motor disorders that can also detail other forms of problems of ataxia, whether it was the REM ataxia as well. That presages or leads to addi- sleep or other aspects of pain or fatigue and tional degeneration. We are beginning to other complements of these diseases that are not understand many of these different elements often talked about. and how they affect the nerve cells in the cere- Dr. Perlman in her usual clear way helped us bellum. We are seeing how the interplay works. understand a lot of what is going on in the Dr. Koeppen did his usual elegant studies sporadic ataxias which are a huge part of this and demonstrations of how the cerebellum is overall disorder, understanding how to diagnose wired and helped us understand again how the them and then understanding how we need Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 17

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to manage them and some of the ideas for the update on some technology and Dr. Wilensky future. in his usual elegant fashion helped us under- Lisa Demers talked about the genetic coun- stand some of the more common elements of seling. I think we are at the verge of having to these diseases and ways to deal with them. do this on a much broader scale. As treatments We have to thank the people with NAF; they are coming down the road we are not going to have been extraordinary in putting this meeting want to wait until somebody’s cerebellum is together. We all know Arnie, DeNiece, and destroyed to find out what they have. At some Char of the Board of Directors and Lisa, Lori, point we are going to need to be screening Bridget, Julie, Jerry, Camille, Becky and people before they are affected. If we have Nicole, whom many of you have met because meaningful treatments for FA (FA is probably they are very active and around. Last but going to be the first one “out of the gate” to certainly not least, the people from the greater have some truly meaningful Boston area support group treatments) we are going to who have been great in run- want to identify people before ning this meeting. NAF has they are symptomatic. That is been involved in things other going to change the way we do than this meeting. Dr. Pulst medicine in order for us to was able to share with us many begin to identify people and of the research efforts that have then what we do with that been undertaken in the last information. We are starting to year, in basic, clinical and do that in other recessive translational efforts. The goal disorders in Minnesota. Just here is to understand the ataxi- two weeks ago we started as so that we can begin treating screening every newborn child them. I am holding up a pic- for Cystic Fibrosis, because ture of the lighthouse and we there are now management can see that NAF is taking the approaches that are extremely Dr. John Day energy of the light from all of helpful for Cystic Fibrosis. We these investigators in an effort better start thinking about it because it is going to channel and focus all that effort into the tar- to start “coming down the pike” soon. When get which is developing, understanding and are we going to start doing that for FA and the diagnosing various forms of ataxia. It is our other disorders and how are we going to impression or understanding, our goal in this manage that? This is a big deal that we are going organization is to channel all of these efforts in to have to start thinking about. Right now the translational, basic and clinical research directed medical system is not geared up for it but it is at at all of these diseases so that we can come up our doorsteps. We are thankful and excited with enough power and energy focused on the about it. If we have treatments we are not going development of treatments. I am honestly more to want to wait until somebody is severely optimistic today than I have been for a long diseased before we start using them. time that we are going to see these diseases Dr. Gerwitz helped us understand the com- brought under control in our lifetime. I hope plexity of these diseases in that FA affects the that during the course of the meeting you have heart. The heart is important in terms of overall been able to get some sense of there being a functioning and the importance of energy “Beacon of Light” as is the theme of the meet- reduction is part of that. Dr. Gomez gave us an ing for us to march onto the future. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 18

Page 18 Generations Fall 2006 Genetic Programs Regulation Cell Fate Decisions in the Rhombic Lip, a Birthsite of Neurons Affected in Ataxia Rebecca L. Landsberg, PhD Harvard Medical School The following is a research summary of a grant funded by NAF for fiscal year 2005.

In this study we analyzed the production of and embryological studies in the mouse aimed brainstem neurons involved in the regulation of at elucidating the genetic pathways responsible balance and coordination. These specific neu- for conferring physiological identity upon ron subtypes arise from a unique pool of neurons of the precerebellar system. progenitor cells in the embryonic hindbrain The precerebellar system is comprised of five known as the rhombic lip. By examining the major nuclei: the pontine gray (PGN) and rhombic lip of embryonic mice with genetic reticulotegmental (RTN) nuclei in the pons, mutations we have begun to understand the and the inferior olive (ION), lateral reticular genetic basis for the development of these (LRN), and external cuneate (ECN) nuclei in critical neurons. the medulla (Fig. 1A). We have shown that Derangements in balance and coordination, neurons populating these critical nuclei origi- the behavioral hallmarks of ataxia, result largely nate from a zone of progenitor cells in the from the selective vulnerability of neurons embryo called the lower rhombic lip (LRL) comprising different regions of the brain. One (Fig. 1B). Previous studies by our lab and others such region is the cerebellum because of its crit- have provided evidence that many of the ical role in maintaining balance and posture as well as coordinating voluntary movement. Another is the precerebellar system, a series of neural clusters (called nuclei) situated in the hindbrain that are involved in regulating balance, coordination, and motor activity by forming connections between the forebrain, cerebellum, and spinal cord (Fig. 1A). In gener- al, a cell type-specific vulnerability to aberrant development and/or degeneration typically Fig. 1: Adult precerebellar system and embry- reflects the specific differentiative properties onic hindbrain. A. Schematic of adult mouse brain unique to those cells, for example, the gene showing relative locations of the precerebellar nuclei in the hindbrain. Heavy arrows (center) represent expression profile of a given cell type. Thus, neural connections formed between the forebrain elucidating the genetic programs that underlie (fb), PGN, RTN, and cerebellum (cb). Light arrows the specification and differentiation of a partic- (right) represent neural connections formed between ular neuronal cell type provides a powerful the spinal cord (sc), ECN, LRN, ION, and cb. B. Schematic of a mid-gestation mouse hindbrain (hb). means to uncover genes that confer upon these The pool of precursor cells known as the lower rhom- neurons a susceptibility to derangement and bic lip (LRL) forms around the fourth ventricle (4v). disease. Using this logic, we conducted genetic mb –midbrain; cb –cerebellum. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 19

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genetics program enacted in the progenitors of the LRL determine the fate of the daughter neurons produced from this region. In other words, the ability to form specific precerebellar cell types appears to be established in progeni- Fig. 2: Loss of Pax6 alters size of precerebellar tor cells of the LRL, thereby pointing to this nuclei. Cross-section through the hindbrains of region as an important site from which to Pax6-mutant (B, D) or control (A, C) late-gestation embryos stained for markers of the ECN and LRN identify specification and differentiative factors (A, B-boxed regions) or ION (C, D). Staining reveals – factors that may ultimately predispose these a decrease in the size of the ECN and LRN and an cells to the vulnerabilities underlying many increase in the size of the ION of Pax6-mutants. ataxias. EMS– extramurally migrating neurons; 4v–4th ventricle; In this study, genetic fate-mapping tech- LRL–lower rhombix lip. niques were used to track sets of precerebellar mouse results in a decrease in the number of neurons from their site of origin (the rhombic neurons populating the PGN, RTN, ECN, lip) to their final position in the mature brain. and LRN (Fig. 2A, B). Our recent studies We identified two distinct, physically separable demonstrated that in contrast to the other progenitor populations in the LRL. The first is precerebellar nuclei, the size of the ION is characterized by the expression of the pro- increased by more than two-fold in the brains neural gene, Math1 and generates the neurons of Pax6-mutant mice (Fig. 2C, D). The of the PGN, RTN, ECN, and LRN but not changes in precerebellar nuclei size in the the neurons of the ION. The second is Pax6-mutant mice were accompanied by alter- comprised of cells that likely generate certain ations in the composition of their respective neurons of the ION and are, in part, character- progenitor pools – the Math1-expressing ized by the expression of the pro-neural gene progenitor population decreased while the Ngn1. We found that the future neuronal Ngn1-expressing progenitor population identities assumed by these two populations of increased. This study provided the first progenitors are regulated by the transcription evidence that Pax6 regulates the development factor, Pax6, a protein that regulates the of the precerebellar system by influencing the expression of other genes. Loss of Pax6 in the future fate of LRL progenitor cells. ❖

So Many Ways to Give There are many ways to support the impor- • Combined Federal Campaign (CFC) tant work of the National Ataxia Foundation. • Fund Raisers Donations are welcomed and needed. Here are • Group Support just a few ways you can help: • Donate a Vehicle • Individual Donations • Memorials/In Honor Of • Annual NAF Memberships • United Way • Annual NAF Research Drive • Surfing the Web with GoodSearch.com • Pledging • Shopping on the Web at iGive.com • Stock Donations • Volunteer • Charitable Gift Annuities Call (763) 553-0020 or e-mail [email protected] • Deferred Giving to find out more about how you can help give to • Employer Matching Gifts Program help those with ataxia. Thank you. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 20

Page 20 Generations Fall 2006 Development of a Mouse Model of Spinocerebellar Ataxia with Neuropathy Cornelius F. Berkoell, MD, PhD Baylor College of Medicine The following is a research summary of a grant funded by NAF for fiscal year 2005. Spinocerebellar ataxia with neuropathy TDP1; therefore, we focused on aims 1 and 3. (SCAN1) is an inherited ataxia. As a conse- See Nature 434:108-113. This study confirmed quence of the brain degeneration, patients are that TDP1 was involved in DNA repair and unable to walk and confined to a wheel chair by that mutations of TDP1 could adversely affect late adolescence to early adulthood. We have gene expression. characterized the clinical features of this disease Aim 3. Generate a mouse model of SCAN1. and have identified the genetic cause as muta- Aim in progress. tions in the gene for the DNA repair enzyme Our hypothesis going into this project was tyrosyl-DNA phosphodiesterase (TDP1). To that SCAN1 was caused by loss of functional understand better the function of TDP1 in TDP1. Therefore to test this, we generated neural development, maintenance, and disease mice that do not express functional TDP1. this end, we proposed: 1) to determine whether Surprisingly the mice were healthy and never other DNA repair pathways that could com- developed ataxia or neuropathy. Although this pensate for the deficiency of TDP1 are might mean that mice are a poor model for expressed in the affected neurons; 2) to identify SCAN1, we tested an alternate hypothesis: the proteins that TDP1 associates with in order development of SCAN1 arises not only from to obtain insights into the pathways that TDP1 loss of functional TDP1 but also requires the functions in; and 3) to generate a mouse model mutations observed in the human patients. In of SCAN1 so that we can study the pathophysi- other words, only specific mutations of TDP1 ology of this disorder in vivo. The progress on will cause SCAN1. each proposed aim follows. Confirming this proposal, our initial studies Aim 1. Determine whether other DNA show: 1) that depletion of mutant TDP1 from repair pathways that could compensate for the SCAN1 patient cells improves the ability of deficiency of TDP1 are expressed in the affect- these cells to repair DNA; and 2) that the ed neurons. Aim completed. mutant TDP1 in SCAN1 cells becomes stuck In yeast two redundant pathways for TDP1 on the DNA and can only be removed by have been well characterized. Components of functional TDP1. Final confirmation of our one of these two pathways are expressed in the hypothesis awaits generation of a mouse same cells as TDP1 and could therefore com- expressing TDP1 that has the mutation found pensate for a deficiency of TDP1. Therefore in the SCAN1 patients. the lack of a redundant pathway in the neurons In summary, this study has more precisely cannot account for SCAN1. defined how mutations of TDP1 cause SCAN1 Aim 2. Identify the proteins that TDP1 and has provided a clear direction for future associates with. Aim completed. studies of TDP1 in the nervous system and for While this work was in progress another generating a model system that will allow us to group published the interacting proteins for test potential treatments for SCAN1. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 21

Fall 2006 Generations Page 21 Mouse Model for X-Linked Congenital Ataxia Joseph Gleeson, MD University of California, San Diego The following is a research summary of a grant funded by NAF for fiscal year 2005. In this project, we proposed to generate a tant work it is doing to promote awareness and mouse model for a gene that was found to be help in the scientific discovery of causes of mutated in some forms of congenital ataxia, the ataxia. One of the major focus areas of my type of ataxia that is seen in newborns and laboratory is in finding the causes for Joubert associated with a disorder in development of syndrome, a disease in which part of the cere- the cerebellum. Creating an animal model for a bellum fails to form. In this condition, children human disease is a critical step in understanding are born with severe medical problems, includ- the basis for the disease, and in developing and ing severe muscle weakness, breathing prob- testing potential therapies prior to their use in lems and ataxia. There is life-long disability and humans. Although these mice are incredible no treatment is available. Through the research important for research to progress, they take as we are doing, we have been able to contribute least a whole year to create and them at least to the knowledge of this disorder by identifying another year to analyze and characterize the the first two genes for Joubert syndrome. These mouse, to see how similar it is to the human genes have unknown function at present, so the disease. Thus we would not expect to have first step is to determine their role in the significant results to report back to the NAF function of the cerebellum. The goal of this within the timeframe of this grant. research project is to improve the diagnosis and During the course of this research project, we treatment of these conditions. I hope that we determined that the initial animal model that can continue to work with the NAF to move we planned to make was untenable because it this research forward. was not as easy as we thought it would be to to Also, I am proud to say that the NAF has shift to creating a mouse model of a different provided important financial and administrative genetic form of congenial ataxia for one gene support for a scientific conference that we are that we recently found to be mutated. This ani- hosting entitled “Cerebellar development: mal model is currently being developed in the Bench to Bedside,” to be held in Washington, lab, and has proceeded smoothly and according DC November 9-12. It will bring together the to plan. We do not have specific details of the world’s experts in how the cerebellum is put results of the experiment yet, partly because together, and the kinds of diseases that can we had to shift to a different mouse model result when this process does not occur correct- halfway through the grant award, and partly ly. This will be the first conference of this type, because of the long time it takes to develop and the timing is perfect because there has been these animal models. We hope to have firm explosion of knowledge about the causes of results in the near future and look forward to these disorders in humans. The NAF has acknowledging the support of the NAF on helped a lot in the support of this meeting, and scientific reports that result from this work. is yet another way that the NAF serves as a I would also like to thank NAF for the impor- catalyst for many types of important research. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 22

Page 22 Generations Fall 2006 SCA26 is Caused by a Mutation in a Vital Protein Synthesis Gene, Which is the Target of Diphtheria Toxiny Guo-Yun Yu, PhD University of Minnesota The following is a research summary of a grant funded by NAF for fiscal year 2005. We previously located the SCA26 lesion on Beyond that H715 of EEF2 is the diphtheria the short arm of chromosome 19. Using candi- toxin-targeting site; we are not clear about the date gene sequencing and methods of standard real biological functions and its posttranslational population genetics, we further pinpointed the modification process of H715. However, recent mutation to a single nucleotide change in a research has linked it to ovary cancer, and cell gene, called protein Eukaryotic translation cycle control. Structure determines functions. elongation factor 2, EEF2 for short. The muta- We believe the SCA26 mutation will have an tion caused a Histidine substitution of a Proline impact on the P715 and its associated biological at position 596 (P596H) in the protein functions. Our discovery of this mutation sequence coded by this gene. This gene is vital provides an excellent opportunity to know to protein synthesis. It happens that this protein more about the ataxia disease at molecular level is also the target of the Diphtheria toxin of the and the real function of the toxin site. We also Diphtheria bacteria. The toxin attacks the found that P596 may be an important CDK5 posttranslational modified Histidine residue at kinase site. CDK5 kinase is a brain-specific position 715 (H715). EEF2 is a well-studied kinase, and it regulates many important func- gene; the crystal structure of the protein for tions in neurons. The mutation P696H may baker’s yeast has been resolved. This gene is have destroyed this regulatory site. In summary, well-conserved, at the protein level, 66% of the we pinpointed the mutation of SCA26 to a vital sequence of the human EEF2 are identical to protein synthesis gene, which happens to be the the yeast EEF2. We expect the two proteins diphtheria toxin target. have similar structure. Using the yeast EEF2’s The vast knowledge accumulated from study- structure as a reference, we found that the ing protein synthesis and diphtheria provides an SCA26 mutation (P596H) is the next-door excellent opportunity for us to understand neighbor of the diphtheria toxin target H715. ataxia. ❖

Tell Your Story in Generations Personal stories are an important part of this stories, poems and photos and will review all Generations newsletter. They give inspiration submissions. and encouragement to our readers. We have Please send materials to the National Ataxia received many letters that have expressed how Foundation c/o Generations, 2600 Fernbrook a single article has changed someone’s life. Lane, Suite 119, Plymouth, MN 55447 or If you have a story you would like to share, we e-mail [email protected]. Please include a SASE if would love to hear from you. We welcome all you would like your materials returned. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 23

Fall 2006 Generations Page 23 YoungYoung Ataxia Ataxia Hero Hero The following letter was submitted by Landon Leger’s fourth-grade teacher.

On Wednesday, April 24th, Landon Leger entertained questions about what he has learned about ataxia, a disease that has affected his family. He attended a conference in Boston where he met many people with different types of the disease. Because he was eager to share his experiences with me, his teacher, Landon lent me a pamphlet so I could understand its causes, symptoms and progression. As we discussed what I read, I asked Landon if he would like to speak to the class about what he knew. He eagerly accepted. Landon invited his classmates to ask him questions about the conference, the disease, his family and his thinking about this issue. While many of the children are aware that Landon’s mother, Stacy, has a difficult time walking and speaking, several did not know why. Those who know that Stacy has ataxia had questions about the origin, progression and symptoms of this neurological condition. Several asked about how Landon feels about his potential to have this disease as an adult. Landon’s candid approach to this serious topic was admirable. He was upfront about his thoughts concerning his family’s experiences and related them to his thinking of others with disabilities. While only nine years only, Landon has a mature outlook regarding this disease. He knows he has the potential to have it as an adult, but his thinking is mature: “I’m not going to worry about it now and ruin my childhood.” Landon is a leader in my classroom and I believe his positive feelings for and comfort with people with disabilities will help his peers to react the same way. As a society we need to be more accepting of those different from us – our society starts with our children, like Landon. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 24

Page 24 Generations Fall 2006

The National Ataxia Foundation 50th Annual Membership Meeting “The Bridge to Hope” Memphis, Tennessee — March 22-25, 2007

The National Ataxia Foundation and NAF scheduling topics and speakers for these sessions Mississippi Chapter would like to invite you to and more information will be supplied closer to join them in celebrating the 50th anniversary the date of the meeting. of NAF –The Bridge to Hope, 1957-2007. The Birds of a Feather – In response to comments meeting will be held on the Mississippi River from last year’s meeting we are going to contin- at the Downtown Memphis Marriott in ue to schedule Birds of a Feather on Friday Memphis, TN. The dates are March 22-25, afternoon. Groups will be sectioned off in 2007. Make your plans to join your friends and individual or divided rooms based on the type enjoy a Memphis breeze. of ataxia, caregivers, parents, etc. This is a Thursday, March 22 tremendous opportunity for you to meet others with your type of ataxia or who share in a This is typically a day for arrival. Many atten- similar situation, and make friends that will last dees come in on Thursday to get settled, rest, or a lifetime. Medical professionals will also be on venture out to see the sights before the start of hand, circulating between groups, to answer sessions. your questions. Leadership Meeting – The Leadership Friday Night Reception – Please join us for a Meeting will be from 1 to 5 p.m. This meeting reception in the Convention Center Ballroom is traditionally for Ambassadors, Chapter for a wonderful NAF 50th Anniversary Presidents, and Support Group Leaders. If you Celebration. All registered meeting attendees are interested in becoming an ambassador or are encouraged to attend and entrance to this support group leader please e-mail Lori ahead event is included with your registration. Make of time at [email protected]. plans to come and celebrate 50 years of NAF. Internet Group – There will also be an More information will be available closer to the Internet Group get-together from 6 to 8 p.m. event. for those interested in meeting others who Saturday, March 24 participate in ataxia chat sites, including ENAF, Internaf, Tricks of the Trade, Ataxia Forum, General Sessions – Saturday morning and Ataxia Chat 2002, and FAPG. afternoon will feature General Sessions in the Convention Center Ballroom. General Sessions Friday, March 23 are large group presentations, typically with a This year’s meeting program format will be a medical or research focus. Many of the world’s little different than last year. Please check back leading ataxia researchers and clinicians, along on our website for updates on Friday’s schedule. with other ataxia experts, will present the latest Workshops & Breakouts – Friday morning, research and additional information. We will both 45 minute and 1½ hour sessions will be also have general sessions on “What is NAF,” available on various topics. We are busy “The History of NAF,” and “What is Ataxia.” Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 25

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General Sessions will be followed by a Question information or call 1-800-228-9290 for reser- & Answer Session. A more detailed schedule vations. Please let reservations know you are will be available soon. with the National Ataxia Foundation group to Church Services – Both Catholic and non- get the $126 standard room rate. Our group denominational services will be held at the code is ATA. hotel if you choose to participate. Service times NAF will be taking ADA room reservations, to be announced soon. NOT the hotel. ADA rooms will fill up fast, so Saturday Evening Banquet – Join us for please contact Lori at NAF by calling (763) dinner and entertainment on Saturday for our 553-0020 to reserve (or cancel) your ADA traditional banquet with a local Southern flare. room immediately. NAF has a limited number There will be wonderful food, fabulous enter- of shower chairs, toilet frames, and tub bars tainment, a raffle for fantastic prizes, and available on a first-come, first-served basis at another chance to get together with each other the Memphis Marriott Downtown hotel front and meet new friends. This evening promises to desk. be full of fun! About Memphis Sunday, March 25 Memphis is the birthplace of the Blues and General Sessions – Sunday morning wraps up rock ’n’ roll. It is the home of Elvis Presley. the conference with the final round of General Originally a sleepy southern cotton town bor- Sessions and a Question & Answer Session dering Arkansas and Mississippi, Memphis now from a panel of speakers. brings music images to mind: an aged blues About the Hotel player strumming a guitar, a young Elvis swivel- ing his hips on stage, and young hopefuls The Memphis Downtown Marriott is located recording their first record in a remote studio. in the heart of downtown Memphis at 250 But this city of great musical heritage has so North Main Street and is close to shopping, much more to offer! museums and night life. There are plenty of free and inexpensive The hotel is 15-20 minutes from the things to do in Memphis. Visitors can take the Memphis International Airport, is an official trolley and walk down historic Beale Street, stop on the Memphis Trolley Line and is con- which offers free music in the park, nightclubs, nected to the Memphis Cook Convention art galleries, museums, restaurants and shops Center. The hotel offers complimentary coffee lining the street. The trolley is wheelchair- and tea in each room as well as a newspaper. accessible with wheelchair lifts at each stop. The Memphis Downtown Marriott features Each trolley car can accommodate two Magnolia Grille with American favorites, wheelchairs and runs every 10 minutes. including a daily breakfast buffet and weekday You can have your picture taken at the luncheon buffet. The Trolley Stop Bar, located Graceland Gates, home of Elvis Presley, and in the lobby, is also available for snacks and visit Meditation Garden, where Elvis, his hors d’oeurves. Recreational activities for parents and grandparents are buried, for free you to enjoy at the hotel include an indoor each morning before 8:00 a.m. You will want swimming pool, complete fitness center, sauna, to visit the Cooper-Young Antique District and and whirlpool. Entertainment District, featuring unique shops, To reserve your non-ADA room please visit boutiques, galleries, and specialty restaurants. It the Memphis Marriott Downtown at www.memphismarriottdowntown.com for more Continued on page 34 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 26

Page 26 Generations Fall 2006 Featured Board Member of the NAF: Earl McLaughlin Earl McLaughlin was born and raised in San Directors and serves as the Board Chair of the Diego, CA. After leaving the Air Force, Earl Fund Raising Committee and Board Chair of attended college at San Diego State University the Abilities Expo Committee. Earl’s commit- where he graduated with honors and received ment and passion in his quest to tell people a BS in Accounting and a BA in Economics. about ataxia and the National Ataxia He later received an MBA in Information and Foundation is seen through his frequent Decision Systems. Earl also has passed the CPA speeches he gives to groups and organizations. exam. Earl stated, “If we (people Earl was a Toastmaster for 13 with ataxia) are not going to years were he achieved the level work hard for NAF, how can of Able Toastmaster (ATM). we expect someone without As a Toastmaster, he won ataxia to do it for us?” Earl is recognition including winning a solid example of how one the Toastmaster’s District 5 person can make a difference. Humorous Speech Contest in Earl has encouraged his compa- 1996. ny and the people he works Recently, Earl retired as with to support the efforts of a Principal Accountant with the Foundation. Many have San Diego Gas and Electric become frequent contributors Company, where he worked and supporters of NAF pro- since 1984. In his free time, grams and events. Earl has been teaching sixth- Earl McLaughlin Under Earl’s leadership, the grade Catholic religious educa- San Diego Support Group has tion for the past 22 years and is active in the hosted three NAF annual membership meet- Knights of Columbus. ings in 1989, 1994, and 2004. The 1989 Earl is married to Renata and both share a meeting was the first time that an NAF annual love of life and commitment in supporting the membership meeting had been located in important work of the National Ataxia California. Foundation. In fact, as Earl says, “I have a When you talk to Earl about an annual mem- vested interest in the success of the National bership meeting his eyes light up. Earl stated, Ataxia Foundation, I have ataxia.” Earl was “If someone does not believe that God lives in diagnosed at a young age with Friedreich’s all people, they have not been to an annual ataxia. meeting.” In 1984 Earl became an active member of Earl began attending NAF’s annual member- the Foundation and in 1986 co-founded the ship meeting in 1986 and has attended every San Diego Ataxia Support Group, the first conference since that time. As he tells those NAF support group. Earl is currently the who are first timers to the conference, “This support group leader. may be your first annual meeting, but not your In 1988 Earl was elected to the NAF Board of last.” Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 27

Fall 2006 Generations Page 27

A Leader Remembered: Kay Bell We mourn the passing of a courageous “what you want will take a lot of work.” Kay’s woman, Kay Bell. answer was, “but it is needed,” and she would Kay suffered for 30 years from a progressive find a way to get it done. She not only served disease called Hereditary Ataxia which, in her on the Board of the National Ataxia case, caused generalized brain atrophy. She Foundation, she used her administrative abili- was unable to walk for the past ties to set up one of their 11 years and needed an in-home national conventions in lift to place her onto her scooter Southern California. due to progressive weakness in Kay was active in getting her arms. She was employed as Gov. Schwarzenegger to sign long as she was able, but the a proclamation for Inter- disease claimed her energy. national Ataxia Day each year. Through all of this she never She was currently trying to complained. She put on her happy get the laws changed so face to all. that many of the sufferers Kay was born in Portland, ME in of ataxia would be covered 1950. Her father was in the mili- under GHPP (Genetically tary, so the family moved around Handicapped Persons Pro- the USA. She lived in Fayetteville, gram) Insurance. NC for 23 years, where she raised She was politically involved. her three children. Her symptoms Kay Bell The Republican Women’s probably began in her late 20’s, Club of Huntington Beach but she wasn’t diagnosed until she moved to honored her several times for putting together Huntington Beach, CA in 1989. their monthly award winning newsletter. Kay Bell founded the Orange County Ataxia Kay is missed terribly by her family. She Support Group soon after her diagnosis. Her leaves her daughters and their husbands, group was featured several times in Diane Karen and Tom Covington and Petra and Terry Rodecker’s column in the Orange County Tyndall, and her son and his wife Paul and Register. She was not a quitter. In fact, doing Helen Bell. She leaves her grandchildren, one thing was never enough. Connor and Alaina Covington, William Tyndall, Being a visionary, she always saw what and Paul and Joan Bell. She leaves one sister, needed to happen next. Others would say Carolyn Campbell.

Earl has given countless hours in his efforts to in making life better for all who are impacted help carry out the important mission of the by the ataxias. As a board member, Earl contin- Foundation. ues to bring forth new ideas and important Through chairing fund raisers, speaking to programs in helping ataxia families. groups about ataxia, raising awareness about “Through the Foundation there is common ataxia through International Ataxia Awareness ground and common good for all of us who are Day (IAAD), and exhibiting at various Abilities affected by ataxia,” Earl stated. “Some of us Expos throughout the country, Earl is a true may have Friedreich’s ataxia, while others may champion of the Foundation and the ataxia have a form of SCA, and others may have an community. unidentified form or a sporadic form of ataxia. Friedreich’s ataxia has had a profound impact Each of us working together has the ability to on Earl’s life. Even with his challenges, he faces support each other to make a difference.” Earl each day with a resolve to continue his efforts leads by example. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 28

Page 28 Generations Fall 2006 Generations Word Find Please see directions and terms at right. Answers appear on page 40.

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Fall 2006 Generations Page 29 NAF’s New Web Site The National Ataxia Foundation launched have choices of its new web site, www.ataxia.org, earlier this font sizes and summer. We welcome all of you to visit the an opportunity new web site and explore. to donate on- The new site offers NAF-funded research line. Check out summaries of studies which are being conduct- the new web ed today, more links, more current issues of site and see the Generations, and a Neurological Resource List changes. of neurologists in your area. You may also want to check back periodically The site also provides you with a site map to because the web site will be getting additional help you navigate through the site, chat rooms phases added. The next phase will be launched and bulletin boards, downloadable fact sheets later this year. on ataxia, and much more. In addition, you See you online! ❖

Word Find Directions Circle the terms defined below when you find them. They can be found across, down, and diagonal.

Antisense DNA: A synthetic DNA strand that is poly-glutamine diseases tend to “clump up” in the complementary to a particular strand of target DNA cell nucleus of affected nerve cells. This suggests that with a complementary sequence of bases. This proteins are not degraded efficiently and accumulate results in preventing expression of the gene encoded. over time. These proteins can be used to selectively turn off Motor neuron: A nerve cell that carries information production of certain proteins or block genetic from the central nervous system to the muscle. instructions. Oxidation: The process by which a substance com- Antisense RNA: It works as described above but is bines with oxygen. This process causes a loss of a complementary RNA sequence that binds to a nat- electrons in an atom and thus there is an increase in urally occurring (sense) mRNA molecule, thus block- positivety of that atom. ing its translation. Proteasome: One of three types of molecules (pro- Apoptosis: Programmed cell death. teasomes, ubiquitins and chaperones) that are Ataxia: Poor coordination. It can be used to refer to involved in protein degradation. Proteasomes break a neurologic symptom which can have many causes protein down for recycling. They act like a cellular or to denote one of several degenerative diseases waste facility. that cause poor coordination. Respiration: A term used by physiologists and bio- Brain Stem: The lowest part of the brain, which chemists, to describe the process of breathing and merges with the spinal cord. It consists of the medul- the intracellular oxidation of substrates (nutrient la oblongata, midbrain, and pons. substances). Gene Frequency: The percentage of a give allele Scoliosis: Sideways curvature of the spine. (gene) in a certain population. Tr a n s g e n e : A foreign that is introduced into an Heterogeneous: A descriptive word that says two organism by injecting the gene into newly fertilized genes are unlike each other. eggs. Some of the animals that develop from the Nuclear inclusions: Also called aggregates. They injected eggs will carry the foreign gene in their are clumps of insoluble protein. Mutant proteins in genomes and will transmit it to their offspring. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 30

Page 30 Generations Fall 2006 Boosting Food Intake What to Do When Appetite is Poor

As the body ages, a person has to make more person under special medical treatment. Special diets of an effort to eat wisely. Most older people and products to improve nutrition should only be need fewer calories, but their bodies absorb used on the advice of a doctor or registered dietitian. fewer nutrients so they must eat high-nutrient Economical and Easy Food Tips food to maintain good health. They must get Pasta and Beans/Lentils more nutrients from less food. Check with the doctor before starting any special diets, espe- Did you know that pasta, along with beans cially for the person with a swallowing impair- and lentils, are among the most economical ment. Also, check with a doctor, pharmacist, or food choices? The good news is that they are registered dietitian to know what effect pre- also good for you and the person in your care. scription medicines have on nutritional needs. Pasta Tips for Improving Nutrition Look at the unit prices on the store’s shelves. • Offer food when the person is most hun- This will tell you how much you are paying per gry, and be sure dentures fit correctly and ounce so you know which one is the least eyeglasses are on. expensive. There is no need to make meat • Encourage the person to sauce for your spaghetti. Plain eat food with the fingers if it old tomato sauce is best for increases intake. your heart and your pocket • Add non-fat powdered book. Most people eat about milk to any food with liquid four times more protein than in it, such as desserts, soups, they need, so skipping the gravy, and cereal. meat is no problem. • Add butter, whipped Did you know that you can cream, or sour cream to make big batches of pasta and foods. then freeze it in freezable • Add cottage cheese or ricotta cheese to storage bags or containers? It is best if you casseroles, scrambled eggs, and desserts. freeze it in small portions for easy reheating • Grate hard cheeses on bread, meats, later on using the microwave. vegetables, eggs, and casseroles. Beans and Lentils • Use instant breakfast powder in milk Beans and lentils are among the best-priced drinks and desserts. sources of protein. They are high in fiber and B • Add nuts, seeds, and wheat germ to breads, vitamins and, unlike animal protein; they don’t cereal, casseroles, and desserts. contain saturated fat or cholesterol to clog your • Add beaten eggs to mashed potatoes, arteries. sauces, vegetable purees, and cooked puddings. Lentils are one of the easiest legumes to cook. • Add honey, jam, or sugar, to bread, milk They don’t need soaking and they cook rather drinks, fruit, and yogurt desserts. quickly – in about 20 minutes. Beans are easy • Add mayonnaise to salads and sandwiches. to cook too. It is best if you soak them in ample NOTE: These may not be the best foods for a water overnight and then cook them the Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 31

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next day. Make sure you add salt or acidic ingredients at the end of cooking so you don’t make them tough. Attention It is a good idea to cook lentils and beans in Federal Workers large batches and then freeze them in small The National Ataxia Foundation is recog- portions for later use. nized to receive funds through the Combined Here are fun and easy ideas you can do with Federal Campaign (CFC). beans and lentils: The Foundation gratefully acknowledges • Add them to salads. When you don’t feel those government employees who have given so generously to the CFC in support of like cooking, toss a few beans with lettuce and the important work of the National Ataxia other veggies and serve your salad with whole Foundation. grain toast. Add them to potato salad or make To contribute to the Foundation through bean salad. the CFC, the designated CFC number is • Make a quick soup. Add cooked beans or 1028. We welcome all government employees to lentils to frozen vegetables and low-sodium V8. contribute to NAF through their local CFC. • Beans and rice. Serve cooked lentils or We also ask that you encourage your co- beans over cooked rice. Season them with a workers to also support the Foundation’s little chili powder and garlic powder. efforts. • Spaghetti sauce. Lentils add hearty flavor and texture to spaghetti sauce. Taking Care of Yourself: Housework is Great Exercise! The U.S. Surgeon General suggests 30 min- Annual Ataxia utes of moderate physical activity at least five Research Drive days per week. Moderate intensity is anything Give help and hope to those affected by that raises your heart rate. Thirty minutes ataxia by contributing to the 2006 National sounds like a lot, but you don’t have to do it all Ataxia Foundation Annual Ataxia Research at once. If your chores increase your heart rate Drive. for 10 minutes or more, you can count it Each research dollar brings us closer to toward your exercise goal. Ten straight minutes stopping ataxia. Please give as generously as you can. of moderate intensity activity three times per day would give you the recommended 30- minute workout. Mowing your lawn with a push mower, moving furniture when you vacuum, chopping Remembering wood, and washing the floor on your hands and knees are all good examples of moderate- NAF in Your Will intensity exercise. Light dusting, washing Today is a gift and tomorrow is not dishes, and ironing are considered to be light- promised. What we do today can change the intensity activities and would not count toward future. your daily activity minutes. So check with your Adding the National Ataxia Foundation to doctor, then go ahead…turn on the radio to your will gives hope for today and a promise for a brighter future. Continued on page 33 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 32

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NAF Merchandise BOOKS VIDEO / CD

“Ten Years to Live” by Henry Schut Ballads of a Family Man CD The story of the Schut family’s struggle with hered- A CD containing 10 songs in memory of Billa itary ataxia and the impact it had on this extended Ballard. $5 of the purchase price goes to support family. Paperback, photos. $8.75 (includes S&H) the work of the NAF. $13 (includes S&H) “Keep A Goin’” by Jeff and Melinda Cromwell “Together there is Understanding” Video Fifty stories about ataxians around the world. A A continuation and expansion of the NAF video portion of the proceeds goes to NAF’s research “Together There is Hope,” this 50-minute video program. Paperback. $13 (includes S&H) provides an in-depth look at ataxia and ataxia “Living with Ataxia” by Martha Nance, MD research. VHS $20 or DVD $25 (includes S&H) New second edition! A compassionate, easy to understand explanation and ideas on how to live SHIRTS / MISCELLANEOUS with ataxia. Paperback. $14 (includes S&H) NAF Denim Shirts “Healing Wounded Doctor-Patient Relationships” Denim with white embroidered NEW! by Linda Hanner and contributor John J. Witek, MD NAF logo. $27.50 Offers demonstrations of how effective dialog can 2006 Annual Meeting T-Shirt help move patients and doctors to productive Vintage long-sleeve with “Beacon of Light” logo. relationships. Paperback. $10 (includes S&H) Sizes XL to XXX-large. $10 Friedreich’s Ataxia Research Cookbook 2005 Annual Meeting DVD or VHS Julie Karjalahti, of Savage, MN, has published this Set of 5 DVDs $75. Set of 4 VHS $50. cookbook to raise money for FA research. Recipes “Ataxia is not a foreign cab” T-Shirts from around the United States. $12 (inc. S&H) White. New design. Sizes small to XXX-large. $10 “Recipes and Recollections”by Kathryn Hoefer Smith “Ataxia is not a foreign cab” Sweatshirts Full of delicious recipes and recollections. Perfect Ash colored. Sizes small to XXX-large. $20 for fund raisers. Proceeds go towards FA research. Window Clings & Bumper Stickers Paperback. $10 (includes S&H) $1 each or 6 for $5 Managing Speech & Swallowing Problems NAF Ataxia Awareness Bands by G.N. Rangamani, PdD, CCC-SLP Blue. One size fits all. $2 NEW! A basic guide to understanding and managing speech and/or swallowing NEW! NAF Ataxia Awareness Ribbon Magnets problems. $7.50 (includes S&H) Blue with white lettering/logo. $4

To order, call (763) 553-0020, fax (763) 553-0167 or mail this completed form to National Ataxia Foundation, 2600 Fernbrook Lane, Suite 119, Minneapolis, MN 55447

Description Qty. Size Each Total NAME: ______ADDRESS: ______CITY ______STATE: ____ ZIP: ______PHONE: ______For credit card orders, please fill out the following information ______(you must include phone number and signature): ______CIRCLE ONE: Visa Mastercard ______NAME ON CARD: ______ORDER TOTAL: ______CARD #:______EXP DATE: ______PLEASE ALLOW 4-6 WEEKS FOR DELIVERY SIGNATURE: ______Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 33

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Boosting Food Intake or a disabled person under age 60. Continued from page 31 • Cannot use kitchen appliances. • Has no motivation to prepare a meal and no great music and do those chores while building caregiver to help cook. a healthier you! • Has become homebound in the winter Source: www.diabetes.org months. Resource for You • Is recuperating from serious illness or The person in your care may be eligible for surgery. the Meals on Wheels program if he or she: For more information, visit Meals on Wheels • Is age 60 or older with a spouse of any age, at www.mowaa.org. ❖ From the Desk of the Executive Director The National Ataxia Foundation began direct giving scientists the keys to unlock the funding of ataxia research in 1978. Over those mysteries of ataxia. years the Foundation has funded hundreds of In the Fall of each year the NAF Medical and studies throughout the world. Each of these Research Advisory Board (MRAB) reviews studies has brought us closer to finding more research applications from scientists through- answers that will help us stop ataxia. out the world. After careful and thoughtful Gene identification, better under- consideration, the MRAB makes standing of gene function, expand- funding recommendations in ed classification of the ataxias, December to the NAF Board of and learning more about the Directors. At the December meet- hereditary and sporadic ataxias ing the NAF Board of Directors are vital steps in finding treat- determines the funding on the ments and ultimately a cure. most worthy research studies for The Foundation has embarked FY 2007 on this journey in funding Over the years a number of vital research, encouraging scientists research studies were not funded to enter the field of ataxia because of lack of financial research, and bringing clinicians resources. That is why it is so and researchers together to uncov- imperative for each and every one er the mysteries of ataxia. Michael Parent of us to support the 2006 NAF Many of the discoveries made Annual Ataxia Research Drive. We have been through research supported by the have seen tremendous research gains over National Ataxia Foundation. Individuals recent years. Let us not lose research opportu- throughout the nation have given generously to nities and fall behind because of lack of fund- support the Foundation’s annual ataxia ing. Your research dollars truly do make a sig- research drives. Individual contributions – your nificant difference in the Foundation’s ability to contributions – are making a difference in the support these essential research studies. fight against ataxia. When you receive your 2006 NAF Annual In October the Foundation will begin the Ataxia Research Drive appeal letter in October, 2006 NAF Annual Ataxia Research Drive. Funds please give as generously as you can. Each received through this drive will be used to sup- dollar brings us one step closer port the most promising ataxia research stud- in ending ataxia. Your support makes all the ies. We are asking for your crucial support in difference. Thank you. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 34

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The Bridge to Hope For more information on these and other Continued from page 37 attractions that Memphis has to offer, please visit the Memphis Convention & Visitors is also home to the First Church of the Elvis Bureau at www.memphistravel.com. Impersonator. The Peabody Place Entertain- ment and Retail Center includes the Peabody Registration Hotel, Beale Street, Fed Ex Forum, the Registration will be open at limited times Orpheum Theatre, and AutoZone Park. during the meetings. Please check in the The center is anchored by a 22-screen Winter 2006-07 issue of Generations and our Muvico Theater complex; Jillian’s a multi- meeting program for registration hours faceted entertainment experience including throughout the meeting. dining, a video café, and sports bar. Peabody Transportation Place also features Tower Records, which offers the latest in music and video and often offers The Memphis Area Transit Authority live entertainment, featuring many Beale Street (MATA) offers public bus service from the musicians. lower outer drive near Terminal C. The airport The historic Peabody Hotel is located here. It route, 32 East Parkway Airport, services the features the march of the famous Peabody airport hourly. To contact MATA direct, you ducks, which takes place daily at 11 a.m. and may call (901) 274-MATA. The Downtown 5 p.m. Afterwards, take the elevator to the roof Memphis Marriott is not located directly on the to see the ducks’ home and the wonderful MATA bus line. views of Memphis. MATAplus is a service designed to meet the The Sun Studio Shuttle is a free shuttle transportation needs of people with disabilities service from Graceland, Sun Studio, Rock ’n’ in the Memphis area. In order to utilize the Roll Museum and Soulsville: STAX Museum benefits of MATAplus, riders must have a of the American Soul Music. The shuttle is disability that prevents them from riding the complimentary but each attraction has admis- MATA fixed route bus system. In order to sion costs. If you require a wheelchair accessible utilize MATAplus service, you need to fill out shuttle, please call Sun Studio at 1-800-441- an application. To request your application or 6249 or (901) 521-0664 to make reservations in to get more information about MATAplus advance. The wheelchair-accessible shuttle is please call 722-7140 from 8 a.m. to 4 p.m., still free of charge, but reservations must be Monday through Friday. made in advance. Arrow Transportation provides wheelchair accessible transportation to and from the Memphis Airport & Memphis Marriot. Tours to local attractions and Tunica, MS are also Please watch for more available. Reservations must be made in Annual Membership Meeting advance by March 1, 2007 and can be made by information and registration forms calling (901) 523-2002 and asking for the National Ataxia Foundation group rate. on our website, www.ataxia.org, Wheelchairs Express is a service for anyone and in the Winter 2006-07 needing wheelchair accessible transportation issue of Generations. to/from the airport. Please make reservations directly with them in advance. The number for Wheelchairs Express is (901) 353-3500. ❖ Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 35

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Letter to the Editor by Martha Harlam Inspired by all the articles of sufferers of testing at the UCLA Ataxia Center for a “rare neu- ataxia, I felt it necessary to share my story with rological disorder” but little was known about it others in the hope that it might inspire someone at the time. It turns out they diagnosed her with to “keep going.” Friedreich’s Ataxia. I was diagnosed at age 34 with Cerebellar I therefore checked in at the Neurological Ataxia. Just at the peak of my powers, the Center of the Cologne/Bonn University Hospital. disease stopped me from pursuing my operatic After an extensive series of tests, a CAT scan singing career in Europe. I had been singing and numerous questions about life style, diet, professionally since I was six years old. After my and stress, plus a spinal tap. After test comple- voice matured, and with intensive classical train- tion, six men in white doctors coats were all ing at University, I went on the audition trail in standing around my bed telling me that I, too, 1973 and landed my first engagement as an had Friedreich’s Ataxia or OPCA, but they weren’t opera singer. My travels with singing took me to quite sure which. The scan was showing grey Germany, Austria, Switzerland, Israel, Great shadings in the cerebellum that were definitely Britan, and, of course, Italy. contributing to my balance, speech, and motor The thought of doing anything other than problems. singing for my supper was no where in my calcu- Now they were all trying to convince me that lations. Until one day as I was crossing a sway- singing on hydraulic stages or managing stair- ing bamboo bridge, some 60 meters above the cases, or walking in costume in high-heeled stage in Madame Butterfly, I felt an uneasiness shoes would have to be a thing of the past. Oh in my gait. I couldn’t tell if the trouble was the sure, I could have gone on singing, but they were swinging bridge or something else. I’d always advising me at age 34 for the future ahead. crossed that bridge, I thought to myself. Tossing Thank God I listened to them. the episode aside I went on with the daily routine Today I have a live-in caretaker who helps me of rehearsals and performances. with everything. I am truly dependent on just Two weeks later I found my balance was off about anyone and everyone to help me maneu- and the ability to maneuver staircases and ver about. But that hasn’t stopped my brain, ramps on stage became fearful chores. I felt heart, and soul! Having moved from the cold of more and more uneasy. Then the real signal Germany to the dry warmth of Spain has made a came when I tried to sing a rapid passage with tremendous difference in the progression of the others on stage and i found myself struggling ataxia. with the articulation of the Italian. The conductor I am active and I use my singing experiences approached me, saying “you were always behind to organize fundraising events for a charity I the beat tonight, please keep up with the rest of created that is determined to establish only the the ensemble.” That was the last straw. I had second hospice on the Costa Blanca Spain. This always been a consummate musician. The very will be a living legacy dedicated to my mother, though of not keeping up with the rest of the who died in a hospice in Florida in 1995 due to singers was terrifying. complication from her ataxia. The Sweet Charity As time went on – almost two months – I Hospice Fund is helping terminal and chronically found myself struggling with all things requiring disabled people and their families receive end-of- fine motor skills and swallowing. That was it. I life care all across the southern part of Spain was off to investigate the problems. The first (see our website at www.hospice-spain.com). It thing I did was call my parents in the States. My is a living testimonial to my mom. mother had always had a history of unbalance, Don’t let the ataxia get the best of you! Inform slurred speech, and problem doing kitchen yourself how to manage the disorder and “KEEP chores. I was aware that she was undergoing ON GOING.”

We welcome your letters and comments. See the inside front cover for contact information. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 36

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Zoo. Fortunately we had a nice cool day. Our Alabama Ataxia Support Group next outing is planned on September 30 and we will visit Stone Mountain which is a giant By Becky Donnelly granite outcropping near Atlanta. We have The Alabama Ataxia Support Group met in found that getting everyone together on an April for a dinner meeting at the Red Lobster informal social basis is a great way see each in Vestavia Hills, AL. The group enjoyed a other and have fun. This year we cut back meal and fellowship together and then heard our formal meetings to four a year so we the exciting news of Dr. Laura Ranum’s dis- could have more social events. covery of the SCA-5 (Lincoln) ataxia gene. The group met again in June at Green Valley Baptist Church in Hoover, Al, for a luncheon and meeting. The group posed for a group picture for use on the quilt for the 2007 NAF Annual Meeting, with a friend of the group, Sandye Nance, as photographer. Other topics included the Ataxia Registry, approval of a welcome letter for use in our Support Group, and Cell Group reports. The program was given by our own Janet Skotnicki, a volunteer with Hand-in-Paw, Greater Atlanta Support Group at the Atlanta Zoo. Animal-assisted Therapy, who brought along We are very saddened to report we lost her Annabell, who brought much delight to one of our members in June. Lauren Kate the group. Loftin passed away on June 27 due to com- The group also made plans to attend the plications resulting from her long battle with Concert for Ataxia Awareness, featuring The Friedreich’s Ataxia. Kate was 24 and very Claire Lynch Band, to be held in Huntsville active in the Support Group. She had also on Saturday, July 22, coordinated by Dianne been named Ms. Junior Wheelchair Georgia Williamson. Many group members and in 2003. Our hearts go out to Bob and Judy friends traveled to Huntsville to attend, and on their loss. to assist Dianne Williamson as needed. It Fund raising is very important, so the was a WONDERFUL evening! The music support group decided to offer a Seven-Night was superb. Thanks for the hard work. Western Caribbean Cruise aboard Carnival Cruise for two. The tickets are $5 and the Greater Atlanta Support Group drawing will be held on November 4. Each support group member is being asked to sell By Dave Zilles at least 25 raffle tickets. We are also going to The Greater Atlanta Support Group held an sell them at a home show in one of the big- outing to the Atlanta Zoo in June. It was a ger malls here in Atlanta. All proceeds will go great time for everyone. We met at a central to NAF and ataxia research. We have plenty location to have lunch and then everyone of tickets, so if you would like to sell some, was able to go off on their own and tour the please let us know. Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 37

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The biggest news is what one of our mem- bers has done to help young disabled adults live more independently. Lynn Robinette, founder of the Wishes-4-Me Foundation, closed on their first group home in July. The house is being renovated to allow three people to reside at the home and have 24- hour care using the community services resources. Lynn’s daughter Robin (22) and Nelda Van Schoick’s daughter Becca (24) plan to be the first occupants. Lynn also The Northeast Florida Ataxia Support Group at the announced that after asking Bob and Judy Captain's Quarters Clubhouse. Loftin for their blessing, the house will be hosts, Ann and Wayne Mayo, along with Liz named Kate’s Home in honor of Kate Loftin. and Dick Ingraham. This concept had been a dream of Lynn’s The next meeting was scheduled for and the Wishes-4-Me Foundation for several September 23. We will have a luncheon at years. It is so important that our young adults the Homestead Restaurant in Jacksonville be able to live the best they can. For more where we will celebrate IAAD. Our speaker information you can go to the website has not been decided as of this date. www.wishes4me.org. We also plan to celebrate International Ataxia Awareness Day with a group signing BC Ataxia Society of the Proclamation with Governor Perdue By Shannon Connors and our annual IAAD picnic at Lake Lanier It has been another busy and successful on Sunday, September 24. year! Along with our annual Christmas party and various outside events we enjoyed many Northeast Florida Ataxia Support Group speakers at our meetings this year. Among By June McGrane them was Christine Gordon of the BC Coalition of People with Disabilities, speaking Our support group meetings convene every on the CSIL program (Choices in Support for two or three months, influenced by holidays Independent Living) at our November meet- or convenience to members. We have had ing. This meeting was well attended and very President Bill Ossmer of the Advocates for informative. A booklet and fact sheets were Disability Claimants, Inc., speak at a recent made available to all attending. meeting. At our January meeting, Dr. Sian Spacey of The June 24 meeting was held in St. the UBC Neurogenetics Clinic came to Augustine at the Captain’s Quarters Club- speak. She explained ataxia and answered house. The speaker for this meeting was many of our questions. In addition, she gave Dr. Nathaniel Whaley, a neurologist with the a slide presentation outlining the research Mayo Clinic of Jacksonville. He covered she is doing on the role of calcium channels many types of Ataxia and research and in the development of cerebellar ataxia. This distributed many charts. He encouraged again proved to be a very interesting and discussions from members and answered informative meeting. Our February meeting many questions. included a discussion of fundraising, a meet- We discussed International Ataxia and-greet and a general question-and- Awareness Day in September and the ataxia answer session. Plans were also made for a quilt for the 2007 NAF 50th Anniversary “Beat the Winter Blah’s Night” at the River Membership Meeting. I will be making the patch. Refreshments were served by our Continued on page 38 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 38

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Chapter & Support Group News were given to me. At that moment, I realized Continued from page 37 not only how much I was appreciated but also that it was these people (members) Rock Casino in Richmond. whose feelings really mattered to me. It was During March, the BC Ataxia Society host- truly a special moment and meant a lot to ed a Tax Seminar for People with Disabilities. me! Eileen Reppenhagen, a CGA specializing in By the time you read this, we will have held this field, conducted the workshop. Eileen our annual picnic. It is once again being spoke about tax credits and deductions for hosted by my husband and me at our home. anyone who has an infirmity or a disability, or Living on a farm with lots of room for parking, for the caregivers who assist them. She no neighbors to bother, and an in-ground spoke for three hours and answered many pool for sun worshippers and lots of shade questions. For more information, visit for others, it is the ideal location. Eileen’s web site at www.taxdetective.ca. This will be my last submission to There was a charge of $10 to attend this Generations as the new executive will take workshop in order to cover speaker expens- over on September 1. As mentioned before, I es. It was a break-even evening but was wish them all the best and thank you again well-attended by creating much awareness for all the support I have received over the for both ataxia and the BC Ataxia Society. years! April and May meetings included discus- sions on issues such as our upcoming Advocacy Forum of the ASENT Meeting fundraiser, donations (made to both NAF and Chesapeake Chapter, Bethesda, MD the UBC Neurogenetics Clinic) and also thoughts and concerns of an across-Canada By Carl J. Lauter cycle ride by a BCAS member. The Chesapeake Chapter represented On May 14 many members also met and itself and NAF at the 5th Annual ASENT joined Bill Lee and his new wife Joan before Advocacy Forum, held on March 9 in they embarked on a honeymoon cruise to Washington, DC. NAF is a member of Alaska. Bill and Joan are from the Maryland ASENT, and we of the CC-NAF like to attend Chapter of NAF. these meetings not only for our own inter- In June we held our Annual General ests, but also to help push information and Meeting (AGM). As expected, I gave my awareness about the ataxias among resignation as President. After more than six researchers, clinicians, pharmaceutical years at the helm and countless hours of facilities, Congress, and the general public. dedicated work, I felt I owed it to myself and This is the third year we have been invited my family as well as to BCAS members. and have attended. Although BCAS was and always will be close We set up an information table in the to my heart, the time had come to step evening among the other advocate groups to down. I had done all that I could and it was provide information pamphlets about ataxia. time to let new blood in. I was excited at the We had several “hits” – people asking about prospect of any change and in helping with ataxia and research grants. About 200 the transition. Most of all, I was excited of research and clinical scientists, medical having the chance to attend a BCAS meeting students, pharmaceutical representatives, and relaxing, without the added stress previ- and government officials were in attendance. ously put on me. The overall theme of this year’s meeting My spirits were raised at a fundraiser we was titled “Emerging Therapeutic Targets for held in July. I received overwhelming support Neuro-therapeutic Development – Delivery from BCAS members and emotions took Systems for the Next Generation.” The entire over at the end of the event when thanks three-day event covered such topics as Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 39

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“Mitochondria, Neurodegeneration and The afternoon sessions dealt with Spinal Neurotherapeutics,” “Alpha-synuclein as Muscular Atrophy (SMA), including topics of Therapeutic Target for Parkinson’s Disease,” “Virtual Drug Development: Role of the Non- “Biomarkers in Clinical Trials for Neurological Profit Sector,” “Biology of SMA,” “Drug Diseases,” “Basic and Applied Science of Discovery for Motor Neurons,” and Stem Cell Therapy,” “The Blood-Brain “Development Considerations in Orphan Barrier: Bottleneck in Brain Drug Disease.” A summary of the afternoon: The Development,” “Challenges in Evaluating unique genetics of SMA have prompted Novel Approaches,” “Globalization of investigation of multiple therapeutic path- Healthcare: How Does the International ways that may be of importance to many Conference on Harmonization Help?” and other disorders including ALS, muscular “Issues for Neurologic Therapies – Problems dystrophy and retinitis pigmentosa. The chal- with the Present System.” We saw that lenges in the search for SMA therapeutics research pertaining to the neurological have led the orphan disease community to diseases is very active and interactive new pathways for drug development in between diseases. neurology. This year’s Advocacy Forum was titled My evaluation is that it was good to see so “Drug Development in Critical Times: The many representatives from a wide variety of Role of Patient Advocates.” As is described organizations representing the various in the program, “ASENT and the patient diseases, which indicates that awareness is advocacy organization groups have a com- of prime importance. mon denominator when it comes to advocat- ing for patients with diseases and disorders The Denver Area Ataxia Support Group of the central nervous system." The leader- By Tom Sathre ship of ASENT is dedicated to building continuing relationships and encouraging The Denver Area Ataxia Support Group communication with the advocacy communi- met on May 6 at Swedish Hospital. ty and the ASENT Advocacy Forum is one Seventeen attended, about half of which way we are fostering those relationships. were ataxians and three were first-timers! The goals of ASENT, as described in the We watched a video summary by Dr. John 2006 program, are to “Provide a forum for Day of the 2005 NAF meeting. We were broadly defined interest areas of academia, highly encouraged by Dr. Day’s statements: government, industry, and advocacy con- it’s good to know such encouraging news cerned with the field of neurotherapeutics; about one of the ataxias. promote dialogue, understanding, and coop- Additionally, it was decided to meet in eration among the interested groups; devel- March, June and September rather than our op information and seek consensus on mat- current meeting plan, which is twice a year. ters; organize education and training for This revised schedule starts in 2007, since healthcare practitioners, biomedical scien- the 2006 meeting plan is already set, with tists, and officials participating in the neu- September 9 being the only time left in 2006. rotherapeutics field,” The latter part of this meeting was given over to discussion about topics for these Presenters this year were Ira Shoulson, meetings. Suggestions were: local trans- MD, University of Rochester; Russell Katz, portation to meetings (AccessARide), a local MD, Food and Drug Administration; Stuart gait clinic, genetic counseling, effective medi- Peltz, MD, PTC Therapeutics; Reijo cations, equipment, financial aspects of Salonen, MD, Pfizer, Inc.; Robert J. Beall, disability and living wills, tinnitus, alternative PhD, Cystic Fibrosis Foundation; and Michael Zigmond, PhD, University of Pittsburgh. Continued on page 40 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 40

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Chapter & Support Group News months of hard work with Fidos for Freedom. Continued from page 39 We were fortunate to have Izzy’s trainers (Paul and Sara Kriedeman) join us for our treatments and diets. In addition, there was meeting. one volunteer for putting together one of these presentations. New England Ataxia Support Group By Donna & Rich Gorzela Howard County Ataxia Support Group As you read this issue of Generations, our By Melba McCarthy & Kathy van’t Hoff group will have already had our barbeque at Sixteen attended the June meeting of the Michael’s and our September meeting at Howard County Ataxia Support Group. Mass. General. Jackie Simmons of Stress Management Michael Martignetti has stepped down as Services in Columbia, MD gave a presenta- our group leader. He certainly has done a lot tion on “Stress Management” which was very for us over the last decade. He even helped informative. start this group! The origin of the word “stress” was in rela- The two of us have been members of this tion to steel – how much stress or weight group for over seven years, and hope we could steel take before bending. Ms. can continue Michael’s inspirational leader- Simmons said that we have been raised to ship! ❖ believe that we have control over our lives; with health problems, that control is impact- ed. We need a support system to discuss and to recognize what we cannot control – Word Find Answers poor health (ataxia). She compared the victims of the disease Here are the answers from the puzzle on page 28.

“ataxia” as people with normal bodies, “just WQ P I WBRA I NSTEMLHGKFG more normal than most.” That is, we all feel BNFOCUVNTVMOWUBXJ ZTW and our bodies react, just slower than most DG J HANT I SENSEDNAUAKP “normal” bodies feel/react. It is an interesting FKBZN CWJ CAXEHMOUCHBR way to compare the changes caused by RA L TT MVOVBNMASGQLHWO ataxia. GSMT I QI NYJUBTWI TYKJT PDBGSCRGWNGEQAUNLPUE Ms. Simmons shared tips to control the E A stress in our lives. For example, she dis- JFOV EAXERSHI PKBEWT EGNUNNKJGDYSCOLIOSIS

cussed the three A’s – Anger, Acceptance, O HTRS L E FWVBQDZ F LGLKO

and Attitude – and talked about how to work N X QFE QSF GHDVENWTTRYM through all three. Also, hope for and work for EJ I U R T A N R ZETRANSGENE a “chronically cheerful” attitude. Try to UQZDNEJP Z E AWUB RCK KU L access the “laugh” portion of your brain. RENEA GSWO W Q HJ I ATOFSN Our newest member is Izzy. This lovely OR I E ST DPGP X U AGPMLYMO young lady has beautiful soulful eyes, black CYT ZDF I QIUT B E RALRHEI curly hair and long shapely legs. She also XI STEZNO FRMO Z N VWJMJT N S C A knows how to shake certain parts of her JWORTKBC XAL B VCLR GHEWGWHKP I UTRI T Y VEXR

body to get attention and show her approval. PLDEQAZCXBWDI XS EMPF I

Her heritage is French. She doesn’t have QR THETEROGENEOUSYU I P

ataxia herself; she is a caregiver. Izzy is REPXASETYPJLQZNRJZTS Tim’s new service dog. We expect to see this N U C L E A R I N C L U S I O N S TME lovely poodle at upcoming meetings and NZR IMOTORNEURONGEOLR events. Izzy comes to Tim after many VHWC YRU I MCQARATAXIAN Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 41

Fall 2006 Generations Page 41 NAF Chapters & Support Groups This is a list of NAF chapters and support groups. The use of these names, addresses and phone numbers for any purpose other than requesting information regarding NAF or joining a chapter or support group is strictly prohibited. We encourage you to contact the chapter or group nearest you.

Chapters California June McGrane 54 Troon Terrace Los Angeles Ataxia S.G. Chesapeake Chapter Ponte Vedra, FL 32082-3321 Sid Luther, President (904) 273-4644 Carl J. Lauter, President 339 W. Palmer, Apt. A 5938 Rossmore Dr. E-mail: jmcgranepvb@ Glendale, CA 91204 bellsouth.net Bethesda, MD 20814 (818) 246-5758 (301) 530-4989 E-mail: [email protected] Orlando Ataxia S.G. (301) 530-2480 FAX Web: www.geocities.com/ Jim Henderson E-mail: [email protected] HotSprings/Falls/6629/ 3212 Lee Shore Loop Web: www.geocities.com/ Orlando, FL 32820 HotSprings/Oasis/4988/ Jim Fritz (407) 568-9092 (310) 397-5208 E-mail: [email protected] Louisiana Chapter E-mail: [email protected] Carla Hagler, President Tampa Bay S.G. PMB 51056 Northern California S.G. Charlie Kirchner 2250 Gause Blvd. Deborah Omictin 306 Caloosa Palms Court Slidell, LA 70461 26840 Edridge Ave. Sun City Center, FL 33573 (985) 643-0783 Hayward, CA 94544 E-mail: [email protected] E-mail: [email protected] (510) 783-3190 Web: www.flataxia1.org Web: http://www.angelfire.com/ E-mail: [email protected] Georgia la/ataxiachapter Orange County S.G. Mississippi Chapter Margaret Ann Hyatt Greater Atlanta Area S.G. Camille Daglio, President 15202 Clemente St. Greg Rooks P.O. Box 17005 Westminster, CA 92683 320 Peters St., Unit 12 Hattiesburg, MS 39404 (714) 892-8468 Atlanta, GA 30313 E-mail: [email protected] E-mail: [email protected] (404) 822-7451 Web: www.geocities.com/ocasgg/ E-mail: [email protected] Dave Zilles Support Groups San Diego S.G. 2400 Kimbrough Ct. Earl McLaughlin Atlanta, GA 30350 Alabama 2087 Granite Hills Dr. (770) 399-6710 El Cajon, CA 92019 Birmingham, AL S.G. E-mail: [email protected] Becky Donnelly (619) 447-3753 16 The Oaks Circle Earl’s e-mail: [email protected] Lynn Robinette Hoover, AL 35244 S.G e-mail: [email protected] 1971 Sumter Court (205) 987-2883 Web: www.geocities.com/ Lawrenceville, GA 3004 E-mail: [email protected] ataxia_sdasg (770) 982-0275 E-mail: lynn.robinette@ Arizona Colorado comcast.net Phoenix Area S.G. Denver Area Ataxia S.G. Illinois Rita Garcia Donna & Tom Sathre 2322 W. Sagebrush Dr. 5902 W. Maplewood Dr. Chicago Area Ataxia S.G. Chandler, AZ 85224-2155 Littleton, CO 80123 Craig Lisack (480) 726-3579 (303) 794-6351 3400 Wellington Ct., Unit 302 E-mail: [email protected] E-mail: [email protected] Rolling Meadows, IL 60008 Tucson Area S.G. (847) 797-9398 Bart Beck Florida E-mail: [email protected] 7665 E Placita Luna Preciosa Northeast Florida S.G. Richard Carr Tucson, AZ 85710 Barry McGrane 120 South Elm (520) 885-8326 9 Arbor Club Drive, Apt. 21-107 Mount Prospect, IL 60056 E-mail: [email protected] Ponte Vedra Beach, FL 32082 (847) 253-2920 Web: www.geocities.com/ (904) 543-1638 azataxiasg Continued on page 42 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 42

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Chapters and Support Groups E-mail: [email protected] Ohio Continued from page 41 Web: www.geocities.com/hcasg/ Central Ohio S.G. Massachusetts Cecelia Urbanski 7852 Country Court Illinois (cont.) New England S.G. Mentor, OH 44060 Donna & Richard Gorzela Southern Illinois S.G. (440) 255-8284 45 Juliette St. E-mail: [email protected] Elaine Darte Andover, MA 01810 36 Lindorf Dr. (978) 475-8072 Peggy Schroeder Belleville, IL 62223 59766 Mount Olive Rd. (618) 397-3259 Minnesota McArthur, OH 45651 E-mail: [email protected] Twin Cities Area S.G. (740) 596-4822 [email protected] Indiana Lenore Healey Schultz 2549 32nd Ave. S. Oregon NE Ind. Cerebellar Ataxia S.G. Minneapolis, MN 55406 Don and Jenney Roemke (612) 724-3784 Willamette Valley Ataxia S.G. 4522 Shenandoah Circle W. E-mail: [email protected] Malinda Moore, CCC-SLP Ft. Wayne, IN 46835 Web: www.geocities.com/ Albany General Hospital (219) 485-0965 twincitiesataxia 1046 Sixth Ave. S.W. Albany, OR 97321 Jenni Pranger Mississippi 3806 Summersworth Rd. (541) 812-4162 Ft. Wayne, IN 46804 See Mississippi Chapter (541) 812-4614 FAX (260) 459-2798 E-mail: malindam@ Missouri samhealth.org Kansas Kansas City S.G. Pennsylvania Kansas City S.G. Jim Clark SE Pennsylvania S.G. Lois Goodman 6605 N. Holmes Liz Nussear 729 S. Clark St. Gladstone, MO 64118 (610) 277-7722 Fort Scot, KS 66701 (816) 468-7260 E-mail: [email protected] (620) 223-1996 E-mail: clarkstone9348@ sbcglobal.net South/North Carolina Louisiana St. Louis S.G. Carolinas S.G. See Louisiana Chapter Mark Bellamy 1306 Cypress Cece Russell Maine Pacific, MO 63069 1305 Cely Rd. (636) 271-6432 Easley, SC 29642 Maine Support Group (864) 220-3395 June West E-mail: mark-bellamy@ sbcglobal.net E-mail: cecerussell@ 56 Ten Penny St. hotmail.com Freeport, ME 04032 Web: www.stlataxia.org (207) 865-4969 New York Texas E-mail: [email protected] Golden Triangle Area S.G. Web: www.ataxiaME.com Mary Ann Costa 460 Brielle Ave Dana Leblanc 2801 W. Sunset #59H Maryland Staten Island, NY 10314 (718) 317-3802 Orange, TX 77630 Howard County S.G. (409) 883-5570 Kathy van’t Hoff, (301) 854-2650 North Carolina E-mail: [email protected] E-mail: [email protected] See South/North Carolina North Texas S. G. or Tim Daly, (410) 715-1241 David Henry Jr. 7 Wentworth Ct. Trophy Club, TX 76262 E-mail: cheve11e@ sbcglobal.net The deadline for Web: www.northtexasataxia.info the Winter issue Utah of Generations Dr. Julia Kleinschmidt Moran Eye Center, U of Utah is November 3 50 N. Medical Dr. Salt Lake City, UT 84132 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 43

Fall 2006 Generations Page 43

(801) 585-2213 E-Mail: julia.kleinschmidt@ hsc.utah.edu Ambassador Listing The following is a list of NAF Ambassadors. Ambassadors are Virginia often in areas not served by a support group or chapter. Please See Chesapeake Chapter get to know your Ambassadors, and if you would like to become Washington an Ambassador please contact the NAF office for an application. Millie Lewendon Alabama Illinois 14104 107th Ave. NE Dianne Blain Williamson Kevin Donnelli Kirkland, WA 98037 123 Leigh Ann Rd. 6525 Thomas Parkway (425) 823-6239 Hazel Green, AL 35750 Rockford, IL 61114 E-mail: mmlewendon@ (256) 828-4858 (815) 633-8620 comcast.net E-mail: [email protected] Kentucky Spokane Area Millard H. McWhorter III Janice Johnson Linda Jacoy P.O. Box 1457 Andalusia, AL 36420 8555 Brownsville Rd. PO Box 19045 Brownsville, KY 42210 Spokane, WA 99217 (334) 222-3423 E-mail: [email protected] (270) 597-3854 [email protected] Albin Douglas Johnson Arkansas 10602 Tarrytowne Dr. Judy and David King Louisville, KY 40272 Electronic 12580 Rivercrest Dr. (502) 995-9003 Little Rock, AR 72212 E-mail: [email protected] Support Groups E-mail: [email protected] Michigan California E-NAF (Electronic NAF) S.G. Lynn K. Ball Mike Betchel 35015 Riverview Dr. Jim Kardos 315 W. Almos #141 Paw Paw, MI 49079 1283 Westfield SW Clovis, CA 93612 (269) 657-5191 North Canton, OH 44720 (559) 292-7763 E-mail: [email protected] (330) 499-4060 E-mail: [email protected] Clare and Patricia Greene E-mail: [email protected] Barbara Bynum 4374 Round Lake Rd. 3801 W. Bailey Laingsburg, MI 48848 Merced, CA 95340 (517) 651-6233 (209) 383-1275 International Minnesota Support Groups E-mail: [email protected] Mike Fernandes Debbie Kelly 7251 Brentwood Blvd. #114 310 Fern St. #7 Canada Brentwood, CA 94513 Big Lake, MN 55309 (763) 263-1812 Alberta (925) 516-6906 E-mail: [email protected] Ellen Moetsch Calgary Darrell Owens 2230 18th Ave. S.E. Andi Birks 917 Paseo Camarillo #717 Rochester, MN 55904 125 Tuscarora Way NW Camarillo, CA 93010 (507) 280-1927 Calgary, Alberta (805) 482-1736 E-mail: [email protected] Canada T3L 2G9 E-mail: [email protected] Julie Schuur (403) 451-9079 218 Cashin Dr. E-mail: [email protected] Connecticut Luverne, MN 56156 (507) 283-2555 British Columbia Terre Di Placito 107 Barton St. E-mail: [email protected] Ataxia Society Vancouver Torrington, CT 06790 Brenda Dixon (860) 489-5092 Missouri 206-8611 Ackroyd Rd Roger Cooley Richmond, B.C. Florida 1609 Cocoa Court Canada V6X 3P4 Christina Sugars Columbia, MO 65202 (604) 273-2789 302 Beach Dr. (573) 474-7232 before noon E-mail: [email protected] Destin, FL 30541 E-mail: [email protected] E-mail: [email protected] (850) 654-2817 Web: www.bcataxia.org E-mail: [email protected] Continued on page 44 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 44

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Ambassadors Angela Cloud Canada 9405 Hwy 6 South Continued from page 43 Susan M. Duncan Houston, TX 77083 #407-1330 Richmond Rd. (281) 693-1826 Ottawa, Ontario K2B 8J6 New York E-mail: [email protected] (613) 820-799 Valerie Ruggiero & Diana Kimmel Barbara Pluta 5 Anna Court E-mail: smduncan1@ 356 Las Brisas Blvd. sympatico.ca Stony Point, NY 10980 Seguin, TX 78155-0193 (845) 786-7471 (830) 557-6050 Cathy Chamberlain E-mail: E-mail: [email protected] 551 Vermilyea Rd. [email protected] (Valerie) Belleville, Ontario [email protected] (Diana) Virginia Canada K8N 4Z5 Diane P. Hall Dick Sargent (613) 962-9623 210 E. Utica St. (703) 321-9143 Prentis Clairmont Buffalo, NY 14208 E-mail: [email protected] 299 Somerset West, Apt. 402 (716) 881-0677 Ottawa, Ontario K2P 2L3 E-mail: [email protected] (613) 864-8545 E-mail: [email protected] Ohio International James Kardos Ambassadors Terry Greenwood 1283 Westfield S.W. 37 Ericsson Bay North Canton, OH 44720 American Samoa Winnipeg, Manitoba R3K 0T8 (330) 499-4060 (204) 885-3955 Bob Coulter E-mail: [email protected] E-mail: [email protected] P.O. Box 9062 Joe Miller American Samoa 96799 India Box 148 (684) 688-2437 Mesopotamia, OH 44439 Abhinav Kedia (440) 693-4454 Australia A9/7A Gomti Apartments E-mail: [email protected] Kalkaji Extension Renee Moore (Nee McCallum) New Delhi-19 Texas 44 Lotherton Way Phone: 0091-011-29960809/ Hocking, W. Australia 6065 Jose Julio Vela 29962759/41861809 61-8-9404-7052 6702 Long Meadow Mobile: 0091-098-18411506 E-mail: moorear@ Corpus Christi, TX 78405 E-mail: abhinav_kedia_2000 westnet.com.au (361) 993-9006 @yahoo.com

If you are interested in International helping ataxia research by donation of tissue Ataxia after death, please Awareness Day contact Dr. Koeppen Many National Ataxia Foundation mem- bers were busy participating in International for information and details. Ataxia Awareness Day (IAAD), held each year on September 25. Arnulf Koeppen, MD Some contacted local political representa- tives, planned awareness ceremonies, set Professor of Neurology up awareness booths, and others planned VA Medical Center fundraisers such as golf tournaments and 113 Holland Ave., Albany, NY 12208 craft shows. Phone: 518.626.6373 If you held an activity for IAAD, please Fax: 518.626.6369 share it with us. Submit your articles for E-mail: [email protected] publication by November 3 for inclusion in the next issue of Generations. Thanks! Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 45

Fall 2006 Generations Page 45 Calendar of Events October 26 Ataxia Society of Vancouver, BC Meeting at 2 Spokane Area S.G. Meeting at Sacred Heart 7 p.m. at the Caring Place, Richmond Hospital in the Mary Bead Room from 5:30 to 28 Alabama Ataxia S.G. Meeting/Luncheon/ 7 p.m. Program from 10 a.m. to 2 p.m. 7 Howard County (MD) S.G. Meeting from November 9 a.m. to noon at Parkinson & Movement Disorders Center of Maryland Conference 2 Howard County (MD) S.G. Meeting from Room, 8180 Lark Brown Rd., Ste. 101 in 9 a.m. to noon at Parkinson & Movement Elkridge, MD Disorders Center of Maryland Conference Room in Elkridge, MD 11 Willamette Valley Ataxia S.G. Meeting from 11 a.m. to 12:30 p.m. at Albany General Hospital 3-5 Abilities Expo – Northern California at the in Albany, OR Santa Clara Convention Center 14 Kansas City (MO) Ataxia S.G. Meeting from 4 Greater Atlanta S.G. Meeting at Emory 2 to 4 p.m. at NE Library, 65 Wilson Ave, Center for Rehabilitation Medicine Kansas City, MO 6 Spokane Area S.G. Meeting at Sacred Heart 14 Main Ataxia S.G. Meeting Hospital in the Mary Bead Room from 5:30 to 7 p.m. 14 Tampa Bay, FL S.G. Meeting from noon to 3 p.m. at Feather Sound Community Church, 8 Utah Ataxia S.G. Meeting and Tour of the 13880 Feather Sound Dr., Clearwater, FL new Moran Eye Clinic Building 14 Northern Texas S.G. Meeting at Las Colinas 8 Willamette Valley Ataxia S.G. Meeting from Medical Center, 6800 MacArthur Blvd., Irving, 11 a.m. to 12:30 p.m. at Albany General TX Hospital in Albany, OR 14 Northern California Ataxia S.G. Meeting 11 Kansas City (MO) Ataxia S.G. Meeting from 2 to 4 p.m. at NE Library in Kansas City, MO 14 Orlando Ataxia S.G. from noon to 3 p.m. at Dr. Phillips Library 11 Los Angeles Ataxia S.G. Pizza Party 14 Pennsylvania S.G. Meeting at Mercy 11 Pennsylvania S.G. Meeting at Mercy Suburban Hospital, DeKalb Pike, Norristown, Suburban Hospital in Norristown in the 2nd PA on the 2nd floor Gerber Room from 10 to floor Gerber Room from 10 to 1:30 p.m. with 11:30 a.m. with lunch to follow lunch to follow 14 New York Ataxia S.G. at Orzac Geriatric 11 Northern Texas S.G. Meeting at Las Colinas Center from 1 to 3 p.m. Medical Center in Irving, TX 14 San Diego Ataxia S.G. Meeting from 1 to 3 11 New York Ataxia S.G. at Orzac Geriatric p.m. at Sharp Rehabilitation Center, 2999 Center from 1 to 3 p.m. Health Center Dr. (behind Sharp Memorial 15 New Jersey Ataxia S.G. Meeting at 7 p.m. at Hospital) Children Therapy Center in Fair Lawn, NJ 17 Twin Cities S.G. Meeting at 7 p.m. at 18 Tucson Area S.G. Meeting Presbyterian Home in Roseville (off 35W on 18 Orange County Ataxia S.G. Meeting from Co. Rd D). Contact Lenore H. Schultz for 2 to 5 p.m. at Newland Street Church of more details. Christ in Garden Grove, CA 18 New Jersey Ataxia S.G. Meeting at 7 p.m. at 18 Tampa Bay, FL S.G/Orlando Ataxia S.G. Children Therapy (Cerebral Palsy) Center in Meeting at Feather Sound Community Fair Lawn (Berkshire Rd. at the corner of 30th Church in Clearwater, FL. This is a joint St.) meeting. The Orlando S.G. is coordinating 21 Orange County Ataxia S.G. Meeting from 2 to a carpool to ensure all can attend. 5 p.m. at Newland Street Church of Christ, 13852 Newland St., Garden Grove Continued on page 42 Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 46

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Calendar of Events 9 Kansas City (MO) Ataxia S.G. Meeting from Continued from page 37 2 to 4 p.m. at NE Library in Kansas City, MO 9 Pennsylvania S.G. Christmas Luncheon 19 Chicago Area S.G. Good Samaritan Hospital 9 Northern Texas S.G. Meeting at Las Colinas White Oak Room from noon to 4 p.m. Medical Center in Irving, TX 19 Tampa Bay, FL S.G. Meeting from 11 a.m. to 10 St. Louis Ataxia S.G. Meeting from 2 to 5 3 p.m. at Feather Sound Community Church p.m. at Meramec Community College, 11333 in Clearwater, FL. Speaker will be Dr. Cheryl Big Bend Blvd., Business Administration Paul from USF Speech and Swallowing Bldg., Room 105, St. Louis, MO Clinic. A Thanksgiving meal will be served. 13 Willamette Valley Ataxia S.G. Meeting from 21 Twin Cities S.G. Meeting at 7 p.m. at 11 a.m. to 12:30 p.m. at Albany General Presbyterian Home in Roseville, MN. Hospital in Albany, OR 23 Ataxia Society of Vancouver, BC Meeting at 14 Maine Ataxia S.G. Meeting 7 p.m. at the Caring Place in Richmond, BC 16 Phoenix Area S.G. Christmas Social December 16 Orange County Ataxia S.G. Meeting from TBA Alabama Ataxia S.G. Cell Group social 2 5 p.m. at Newland Street Church of Christ outing in Garden Grove 2 Carolinas Ataxia S.G Meeting from 11 a.m. 18 Twin Cities S.G. Meeting at 7 p.m. at to 3 p.m. at Bible Baptist Church in Presbyterian Home in Roseville, MN Matthews, NC (near Charlotte) 20 New Jersey Ataxia S.G. Meeting at 7 p.m. at 2 Howard County (MD) S.G. Meeting from Children Therapy Center in Fair Lawn, NJ. 9 a.m. to noon at Parkinson & Movement 28 Ataxia Society of Vancouver, BC Meeting at Disorders Center of Maryland Conference 7 p.m. at the Caring Place in Richmond, BC Room in Elkridge, MD 2 Orlando Ataxia S.G. from noon to 3 p.m. at January 2007 Dr. Phillips Library 13 Northern CA S.G. Meeting at 11:30 a.m. at 4 Spokane Area S.G. Meeting at Sacred Heart Our Savior’s Lutheran Church (Recreation Hospital in the Mary Bead Room from 5:30 Hall), 1035 Carol Lane, Lafeyette, CA. to 7 p.m. Contact Deborah Taylor Omictin for more details. 16 Twin Cities S.G. Meeting at 7 p.m. at Young Adult Presbyterian Home in Roseville, MN February Ataxia Group 17 Chesapeake Chapter Annual Medical Meeting from 9 a.m. to mid-afternoon at the on MSN Theater Arts Center, Montgomery College, There is a new Ataxia Young Adults Group Rockville, MD. Contact Carl Lauter for more on MSN. details. If you are a young adult and would like to 20 Twin Cities S.G. Meeting at 7 p.m. at chat with others about ataxia, come check Presbyterian Home in Roseville, MN us out at http://groups.msn.com/Ataxia- YoungAdults. March You will find areas for Chat, Messages, 20 Twin Cities S.G. Meeting at 7 p.m. at Pictures, Calendar and Links. All you need to join is a free Windows Live ID. Presbyterian Home in Roseville, MN Help yourself and help others by sharing in 22 NAF Leadership Meeting in Memphis, TN our Young Adult Ataxia Group. Visit today! 23-25 2007 NAF Annual Membership Meeting in Memphis, TN Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 47

Fall 2006 Generations Page 47 Memorials and In Your Honor The National Ataxia Foundation is grateful to those who have made contributions in memory or in honor of their friends and families whose names are listed below. This list reflects contributions made from May 2006 through July 2006. We are sorry that we cannot separate the memorial contributions from those made in honor of someone, as sometimes the person making the contribution does not let us know if the contribution is a memorial or in honor of their friend or family member. Alexander Family Crawford Family Marybeth Mullaney Family Windy Smith Beth Asp Walter Croxton Kolanowski Kaela Mullaney Abbie Spellman Denise Drake- Tova Daniels William Keaveney, Carol Murphy Charles Stebbins Asselin Charlene Sr. William Murphy Cathy Steward Robert Keithly Joan Augustine Danielson Robert Mutschler Sylvia Stiefermann Florence Kettner Sharon Baggett John Day Helen Myers Linda Stine Matthew Kraft Jeffry Bailey Ramiro Del-Real Bruce Nanninga Juanita Sundberg Pat Dominy Sabine Kuntze Cheltzie Baker Delbert Olberding Sheila Suriano Fred Donnelly Marlene Kusumoto Vicki Balogh Marge Olberding Kory Tabor Sandy Dudzic Rodger Larsen Donald Banta Vernie Page Scott Tabor Duffy Family Denise Laundy Aklish Parmeswar Elwood Barley Fayne Thiel Violette Barr Ronald Eakins Herb Lee Shirley Perret Leslie Tobias Barton Beck James Ellson Linda Lee Quincy Powers Kenneth Esch Lisa Lee Dr. Amyee Torres- Betty Beck Stephen Price Michels Floyd Eustache Pam Lee Amy Pridmore Clair Beck Jesse Tucker Pat Fagg Amy Lenahan Linda Reetz Kay Bell Carol Tylar Joseph Falcon Sylvia Lindsey Carl Regutti Jerry Bender Carol Unnewein Katherine Falcon Peggy Littlejohn Grace Regutti Zohar Birin Frank Vaccarella Kim Bishop Janet Fariel Kate Loftin Juanita Remond Mary Vida Philip Blackmore Rita Garcia Bob Lubbe Laura Renn Matthew Warren Linda Bowen Anneke Geluk Deborah Markham Mary Reyes Susan Weiler Gordon Boyles Patricia Greene Lisa Marsh Dr. George David West Carol Brand Paschal Guercio Bradley Masserant Rieman, Jr. Carol Haley Joyce Robbins Martina Wiese Jane Brewer Bradley Masserant Dynah Haubert Family Nathan Robinson Connie Wolff Edgar Brown David Hazelgrove Victor Masserant Ricardo Roca Ronnie Wright Lula Brown Sharon Family Madalyn Rogers Anne Wynne Madeline Brown Hazelgrove Elaine Maxey Ainslee Santa- Thomas Wynne Willis Brown Jeffrey Helman Harold Maxey Croce Dennis Yosick Chris Buechel Michael Helman Darrin McCarty Donald Santa- Nathan Young Janice Buuck Croce Marie Helminiak Charles Ryan Young Kenneth Canter Alan Hendley McLaughlin Blaise Santianni Andrew Carey David Henry, Jr. Earl McLaughlin Larry Schut Support Groups Richard Carr Judith Reggie Mellon Loretta Schut BC Ataxia Society James Christman Hoffenberger Refiye Miller Rebecca Schutte Chicago Area Frank Coffey Johnny Hogan Minnie Molini Robert Schnefer, New England Claire Costa William Huber Clarence "Pookie" Jr. Johnny Costa Jeans Day Montecino Sherry Sharp N. California Debbie Covington Fundraiser Dolores Morello Joan Sigmon Orange County Dr. William Frances Johnson Joyce Morelock- Marvin Smith Phoenix Area Covington R. Jurasek Rector Robin Smith San Diego Gen_0603.qxd:Gen_0603.qxd 9/26/06 9:47 AM Page 48

National Ataxia Foundation Non-Profit Organization 2600 Fernbrook Lane, Suite 119 U.S. Postage Minneapolis, MN 55447-4752 PAID (763) 553-0020 Madison, SD Permit No. 32

Is your address correct? Are you receiving more than one issue of Generations? If there are any changes that need to be made, please call NAF at (763) 553-0020. Thank you!

GIFT – HONOR – MEMORIAL MEMBERSHIP A contribution given in memory of a friend or Yes, I want to help fight ataxia! Enclosed is relative is a thoughtful and lasting tribute, as my membership donation, which enables NAF are gifts to honor your friends or family. A Gift to continue to provide meaningful programs and Membership is a wonderful gift to a friend or services for ataxia families. (Gifts in US Dollars) relative for a special occasions like birthdays, ❑ Lifetime membership $500 + graduations, anniversaries, and holidays. NAF Annual memberships: will acknowledge your gift without reference to ❑ Patron membership $100-$499 the amount. ❑ Professional membership $45 + Simply fill out this form and mail with your ❑ Individual $25 + check or credit card information to the National ❑ Household $45 + Ataxia Foundation. ❑ Addresses outside the U.S. please add $15 Honor/Memorial envelopes are available free Your Name ______of charge by writing or calling NAF. Address ______My contribution is: City/State/Zip ______❑ In Memory ❑ In Honor ❑ Gift Membership E-Mail ______Name ______Occasion ______PAYMENT INFORMATION Gifts are tax deductible under the fullest extent of the law. Send Acknowledgment Card to: ❑ Check. Please make payable to the Name ______National Ataxia Foundation. Address ______Total Amount Enclosed $ ______City/State/Zip ______Credit Card: ❑ Visa ❑ Master Card Name on Card ______From: Card # ______Name ______Exp. Date______Address ______Signature ______City/State/Zip ______Phone Number ______