Ge neratio ns The Official Publication of the National Ataxia Foundation Volume 35, Number 2 Summer 2007 Ata xia Resea rch Review By Harry Orr, PhD Dr. Harry Orr is a full professor for the Department of Laboratory Medicine and Pathology at the University of Minnesota Medical School. Dr. Orr received a BA degree from Oakland University in Rochester, Michigan. He earned his P hD at Washington University and completed a graduate fellowship at Harvard. He is the Director of the Institute for Human Genetics and holds the Tulloch Chair in Genetics. Dr. Orr is known as the researcher who, along with Dr. Huda Zoghbi, found the first gene for ataxia, now known as SCA1. His research is focused on molecular neurogenetics and he is a published author of more than 120 articles, many on the genetics of ataxia. Dr. Orr was appointed the National Ataxia Foundation’s Research Director on June 14, 2006. The following was presented at the 2007 NAF Annual Membership Meeting in Memphis, Tennessee. I have two major goals in this short talk this that the goal here is a treatment or cure for ataxia. morning. One is as Director of Research for the Of course, it needs to be stated that the founda - National Ataxia Foundation: I want to give you tion of this effort is you, the patients and families an overview of ataxia research from the perspec - with ataxia. tive of the meeting today. Clearly, my colleagues Now just a few specific words about the that are coming up after me, after the break, will different types of research. We start with basic give you a much more detailed perspective of a research. This is where we try to find in the lot of the exciting research that is going on in research laboratory the cause of ataxia. What we ataxia. Besides being the Director of Research are looking for, as researchers, are the cellular and for the National Ataxia Foundation, I also head biochemical pathways that are altered as a result up a lab that does research on ataxia, specifically, of the disease. From this information, still in the SCA1, so I thought I would take a moment research lab, we move towards what we call towards the end of the talk to give you a few preclinical research. This is where we test ideas words about where we stand in terms of SCA1. for therapies and largely we test these in model We view research as the bridge to hope. On systems of the disease and we rely very heavily one side of the bridge, the left hand side, we have on the use of animal models. In my own lab we two major classifications of research starting out rely exclusively on the use of a mouse model of with basic research and moving to pre-clinical the disease that we study. There are two types of research. As we move across the bridge we move into clinical trials, and obviously we all are aware Continued on page 3 Page 2 Generations Summer 2007 Please direct correspondence to: Gen erations Staf f: National Ataxia Foundation Julie Braun ..................................... Financial Director 2600 Fernbrook Lane, Suite 119 Sue Hagen ................................ Outreach Coordinator Minneapolis, MN 55447-4752 Becky Kowalkowski .............. Patient Services Director Phone: (763) 55 3- 0020 Mike Parent ................................... Executive Director FAX: (763) 55 3- 0167 Lori Shogren ................... Special Projects Coordinator Internet: www.ataxia.org Donna Gruetzmacher ..................................... Advisor E-mail: [email protected] Design, Production and Printing .............. Leader Printing Generations is published by the National Ataxia Foundation, Inc., Minneapolis, MN. Copyright 2007 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 National Ataxia Foundation does not endorse products, services, or manufacturers. Those that are mentioned in Generations are included only for your information. The NAF assumes no liability what - soever for the use or contents of any product or service mentioned in the newsletter. Table of Conten ts Annual Membership Meeting Articles (cont.) Ataxia Research Review ................................. 1 Stock Talk .................................................. 42 Experimental Therapeutics for New NAF Research Program for FA ............... 45 Friedreich’s Ataxia ......................................... 7 International Ataxia Awareness Day .............. 46 Other Movement Disorders in Shopping on the Web .................................. 47 Patients with Ataxia ..................................... 16 Photographs .......................................... 24-26 Research Summaries Blazing a Trail in Researc h: How Does the Normal Function of 2008 Annual Membership Meeting ............... 27 Ataxin-3 Affect Its Fate in Cells? ................... 32 Characterization of Frataxin’s Articles Function in the Stress Response: NAF Giving Options Abound ............................ 6 Taking Advantage of C. Elgans Model ........... 34 From the Desk of the Executive Director ....... 13 Membership Topics Caregiver’s Corner ....................................... 14 NAF Merchandise ......................................... 33 Taking Care of Yourself: Chapter and Support Group News ................. 36 Good Nutrition is Essential and Easy ............ 15 NAF Chapters and Support Groups ................ 38 Generations Word Find ................................ 20 Ambassador Listing ...................................... 41 American Academy of Neurology Conference a Huge Success ........................ 22 Calendar of Events ....................................... 43 Designate Your Research Dollars ................. 22 Memorials and In Your Honor ........................ 47 Family Fund Raisers .................................... 22 Personal Stories and Poems Thank You Athena! ...................................... 29 Murphy’s Gramma ....................................... 12 Featured Board Member I’m Living with Ataxia: of the NAF: Camille Daglio ........................... 30 the Sneak Thief of Life ................................ 23 A Special Thank You to Dr. Susan Perlman ... 31 My Group .................................................... 39 Attention Government Workers ..................... 32 Summer 2007 Generations Page 3 Ataxia Research Review sporadic ataxias and inherited ataxias. We all Continued from page 1 know that if we have a sporadic ataxia, your children are at no increased risk for developing tests that we do in the lab. One test is what we ataxia. Whereas if you have an inherited form of call a proof of principle and this is where we use ataxia, you have gotten the mutated gene from a strategy where we are basically asking the one or both of your parents and if you have question, if we were able to alter this function, children they are also at risk for inheriting this and typically we are using a strategy that we can mutant gene. In the research arena, we focus only use in the research lab, but if we alter this a lot of our attention on the inherited or the function is it a benefit in the disease model. The genetic forms of ataxia. Often it is hard to second, and perhaps more important type of understand why we focus so much attention in preclinical research, is where we are using an our research on these forms of ataxia and less so approach that we think has the possibility of on the sporadic ataxias which, if anything, are being applied to humans. And so, again does this more frequent than the genetic forms. The approach have a positive affect on the disease in simple answer is that we know from a research our animal model? And if in the result of this side how to go from a mutated gene towards preclinical research things go well, we then move understanding the molecular pathway that is forward to what we call clinical trials and this is altered. That is a much more difficult question to where we actually test these potential therapies or therapeutics in humans. address for the sporadic forms of ataxia. So for the inherited ataxias, the roadmap if you will, the I am sure you have heard the different desig - map for research, is to start with families, find nations for clinical research: phase one, phase the gene, understand the mutation and with that two and phase three. These are the trials that are information begin to elucidate the pathways in overseen by the FDA, the Federal Drug Admin - istration. In phase one, the simple question is, the cell that are altered as a result of this mutant “With this drug, what are its toxic effects?” You gene. have heard previously that every drug comes You are going to hear in subsequent talks, for with side effects and comes with toxic effects. example in Friedreich’s ataxia, we know the We are putting chemical agents into the body mitochondria is a major target, the part of the and we basically need to get a handle on what are cell that produces energy. In other forms of ataxia these toxic effects. The basic question is we want we think the nucleus might be the major target to be assured that the drug is certainly no worse of the mutant gene, the region of the cell that than the disease itself. Once a drug or thera- contains our genetic information and controls peutic passes phase one, it moves to phase two. how that genetic information is expressed. Once This is where we begin to ask the question, we understand these molecular pathways, we can “Does this drug have some potential to be effec - then move to therapeutics. Now the hope is tive to treat the disease that we are interested in?” that as, and I think it is being borne out as the If we pass phase two, we move onto phase three, research is progressing, we understand and get which are the large scale clinical trials where we therapeutics for these genetic forms of ataxia are really trying to hone in on how good is this they will also be effective for the sporadic forms drug for therapy in terms of ataxia. Then, of of ataxia. So although the research is perhaps course, if it passes phase three we have a treat - different between the two types of ataxias the ment that can be prescribed by your physician. outcome, hopefully, will be the same.