Friedreich's Ataxia

FAST FACTS About FA

This special report, written in December 2010, outlines the latest findings in Friedreich’s ataxia (FA), an inherited neurodegenerative disease affecting approximately one in every 50,000 people in the United States.

First described by German physician Nikolaus Friedreich in 1863, FA mainly affects the heart and nerve cells of the brain and spinal cord, as well as the peripheral nerves.

FA affects males and females equally. It typically manifests in the early teens but has been diagnosed in some as young as 2 In Focus: Friedreich’s Ataxia years old and in others as old as 50. Symptoms vary in onset and speed of progression, but typically Table of Contents include loss of balance and coordination (ataxia), and muscle weakness that begins in the legs and torso and spreads to the • FA: A Case of Impaired Ironworks...... 2 arms and hands. Some experience difficulty with speech and • Idebenone Clinical Trials (Chart)...... 9 swallowing, muscle tightness (spasticity), loss of sensation and • Everything is Treatable, skeletal abnormalities. FA’s effects on the heart range from mild Even if Not Yet Curable...... 14 to life-threatening. • Treating the FA-Affected Heart...... 18 • Strategies to Improve FA-Affected FA has a recessive inheritance pattern, requiring two gene flaws Speech...... 20 (one on each chromosome, each from one parent). An individual • Physical Therapy for FA: Practice, who has only one abnormal copy of the gene is a healthy Practice, Practice...... 23 asymptomatic carrier and can, in turn, pass on the affected gene • Profiles of People with FA...... 24 to offspring. — Gabrielle Ford, 30, Fenton, Mich. — Nygel Lenz, 36, Clearwater, Fla. Since 1975, MDA has invested more than $12,056,711 in FA — Bridget Morris, 19, Littleton, Mass. research. The Association’s current commitment through 2013 — Pinky Patel, 28, Paducah, Ky. includes 10 grants totaling $2,030,758. — Kayla Prather, 17, Hiram, Ga.

rom childhood science classes, Too much iron, or iron overload, support. Fyou may remember the peri- is toxic, with a broad range of odic table listing all the known effects that may include cell dam- Bidichandani, also a former mem- chemical elements. You might also age, organ damage (such as in ber of MDA’s Medical Advisory recall, in approximately the center the pancreas, heart and brain), Committee (MAC), noted that pin- of the table, the symbol “Fe” signi- metabolism problems and neuro- pointing the gene was particularly fying the metal iron. degenerative disease. difficult. While a majority of genetic diseases are caused by mutations Produced inside large stars in dis- The inability to properly manage in the “coding” regions, or exons, tant space, iron is the most com- iron lies at the heart of the neuro- of genes (that is, the parts of the mon element on Earth. From earli- degenerative disease Friedreich’s gene that carry instructions for pro- est times, humans have used it in ataxia (FA). tein synthesis), the defect respon- everything from paint pigments, sible for FA turned out to reside in cookware and tools to buildings, Finding the FA gene a “noncoding” region of the gene, bridges and cars. or intron. In 1996, two teams of scientists — Longer still, humans have relied one led by then-MDA-grantee Genetic mutations in FA on iron as a biological workhorse, Massimo Pandolfo at Baylor necessary for survival. College of Medicine in Houston, Although two types of FA-causing and the other by Michel Koenig mutations exist, by far the most Iron-containing proteins are in France — published their dis- common is a GAA trinucleotide involved in a vast array of vitally covery of the underlying molecu- repeat expansion — a region of important functions in the body lar cause of FA: an expanded DNA containing greater-than- including: sequence of extra DNA in a gene normal numbers of the chemical on chromosome 9. The gene car- phrase “GAA.” • formation of red blood cells; ries instructions for production of • oxygen transport via blood and the frataxin protein. Five to 30 GAA repeats are within oxygen storage in muscle; and normal range, but in people with • cellular energy production. It wasn’t an easy find, but it was FA the repeats number in the hun- the crucial first step in providing dreds to thousands, with the larger Distribution and storage of iron is researchers with targets at which repeat expansions generally corre- carefully balanced and regulated to aim therapies for the disease. lating with earlier onset and greater by cells. disease severity. “Finding the gene — it was a Too little can result in iron defi- big, exciting time,” recalls Sanjay Approximately 96 percent of peo- ciency anemia, characterized by Bidichandani, MDA vice presi- ple with FA have two GAA repeat weakness and fatigue, and impair- dent for research, who was part expansions, one on each chromo- ment to the immune system. of Pandolfo’s team on the gene some. The other roughly 4 percent identification project, with MDA possess two different mutations: an

2 In Focus: Friedreich’s Ataxia ©2010 MDA expansion on one chromosome, “the genetic instructions will allow understand the details of how it’s and a conventional gene mutation production of a perfectly normal accomplished at the molecular (most of which are truncations, or frataxin protein.” and atomic levels, but I think the deletions) on the other. main function of the protein is well- Frataxin’s function known.” Importantly, every individual with FA has at least one GAA expan- The frataxin protein does its work What is agreed upon — at least sion mutation, which has important in mitochondria, the energy-pro- by most — is that in FA, the phys- implications for therapy develop- ducing “powerhouses” in cells. ical increase in the amount of DNA ment. in the gene for frataxin directly or Although the protein is present in indirectly results in a decrease in “There has never been a single all tissues of the body, “only cer- transcription of instructions into Friedreich’s ataxia patient reported tain cells are exquisitely sensitive RNA and, by extension, decreased to date who has conventional, to frataxin depletion,” says Grazia levels of frataxin. or point mutations on both chro- Isaya, professor of biochemistry mosomes,” Bidichandani says. and molecular biology and pediat- Why isn’t there enough “That’s important when it comes to rics at the Mayo Clinic College of frataxin? developing therapeutic strategies, Medicine in Rochester, Minn., and because it implies that treatments a member since 1998 of MDA’s The first mechanism posited to targeted to the repeat or its con- Medical Advisory Committee. explain the decrease in frataxin sequences should apply to every These include cells in the heart transcription was proposed by patient that exists.” and pancreas, and large sensory Massimo Pandolfo and colleagues neurons (nerve cells) associated when they initially identified the The location of the GAA expan- with the spinal cord. GAA expansion. sion in an intron holds additional positive implications for treat- “In fact, even in the central and The group theorized that the ment because the exons and the peripheral nervous system, there repeats would form an abnormal protein-making instructions they are only certain neuronal cells “triplex” DNA structure, one variant contain are left unaffected. The that are particularly susceptible to of which was dubbed “sticky DNA.” introns are removed, or “spliced frataxin deficiency,” Isaya explains. out,” in the RNA stage (the inter- “Maybe other tissues are sensitive Such abnormal structures have mediary step between DNA and as well, but not to the extent that it been shown in bacterial and vari- protein synthesis in cells). becomes clinically obvious — and ous mammalian cell culture mod- we do not yet understand why this els to reduce transcription. The implications of this particular is the case.” sort of defect are “enormous,” “So these early data showed that says Pandolfo. People with FA Isaya cautions that the basic func- the expanded GAA repeat was “have the disease because they tion of the frataxin protein is a capable of reducing frataxin RNA make too little of a protein, fratax- polarizing topic among researchers production,” Bidichandani says. “In in, but the protein they make is in the field, with some maintaining other words, no other factors, such normal. that frataxin’s function is not yet as epigenetic modification [a sort known. of biochemical gene regulation “So, if one can boost its synthesis, mechanism], are necessary.” the basic defect in the disease “My view is the opposite. I think may be corrected.” we understand the basic func- More recent work indicates that tion of the protein, which is to the GAA expansion also regu- In other words, “if we can bypass bind iron and make it available lates activity of the frataxin gene the problems caused by the repeat to other mitochondrial proteins,” through epigenetic controls that expansion,” Bidichandani explains, Isaya says. “We certainly don’t cause gene silencing.

3 In Focus: Friedreich’s Ataxia ©2010 MDA Iron overload and the mitochondria become iron- loaded at the same time other areas Over the last several years, MDA of the cell exhibit iron deficiency. grantee Des Richardson and colleagues at the University of Sydney, “It’s a paradoxical situation,” Isaya Australia, have focused on pinpoint- says. “The cells feel that they are ing the pathways that lead to iron depleted of iron, when in fact they’re accumulation. accumulating it in the mitochondria.”

In 2008, the group published study Oxidative stress Chromatin structure affects gene activation. Closed, results describing the downregula- or condensed, chromatin restricts access to the gene, tion of three iron-trafficking pathways In addition to the disruption of ISC while open, or relaxed, chromatin allows the cell’s machinery to access the genes and make proteins. caused by decreased frataxin pro- and heme generation, and inappro- duction: mitochondrial iron storage, priate iron levels, the problem of iron iron-sulfur cluster (ISC) synthesis overloading in the mitochondria can In the case of FA, this involves and heme synthesis. lead to extensive cellular damage via compacting chromatin, the structure oxidative stress. formed by DNA and the proteins ISCs and heme are important mol- that DNA is wrapped around, called ecules that drive a number of vital Because the mitochondria are histones. cellular processes affecting every unable to direct the binding of iron compartment and a number of differ- with proteins to make the complexes With such “condensed” chromatin, ent pathways in the cell. necessary for ISC or heme synthe- DNA is closed, preventing the cell’s sis, iron is left “free,” able to induce protein-building machinery to access “Normally, iron comes into the mito- the conversion of energy-production the genetic instructions. (See the chondria, and it’s utilized very effi- byproducts into toxic chemicals January 2010 Quest magazine arti- ciently for the synthesis of iron-sulfur called free radicals. cle Epigenetics: Above and Beyond clusters and heme,” Richardson Genes.) explains. “It comes in, it incorporates When produced in excess, or when into the ISCs, incorporates into the cells become unable to detoxify “With the epigenetic story, you get heme, and then very quickly these them, free radicals become danger- a closed chromatin formation near complexes are shuttled out, back ous, causing extensive damage to the expanded repeat sequence,” into the cell.” cellular structures, including DNA, Bidichandani explains. “We also and eventually killing the cell. have new evidence that this might Without frataxin to handle iron safely be occurring near the area of the and efficiently, mitochondria are no Among the variety of outcomes gene where transcription starts as longer able to generate the ISCs associated with iron-triggered free well.” and heme. When the cell detects the radical activity are heart disease and problem, it senses it as a situation of neurological problems. The two mechanisms — abnormal iron insufficiency and works to fix it DNA structure and epigenetic gene by bringing more iron into the cell. An understanding of free radical silencing — aren’t mutually exclu- damage led to some of the first treat- sive and may in fact overlap. On its surface, the cell increases ment strategies for FA. the levels of a molecule called the In any case, decrease of frataxin transferrin receptor, which brings in FA treatment strategy: RNA leads to decrease in frataxin more iron from a protein in the blood Antioxidants protein production, which in turn called transferrin. leads to abnormal iron overload and Antioxidants are drugs designed metabolism in the mitochondria. The iron is targeted to the mito- to offer some protection against chondria, but when it gets there it’s free radical damage in cells and to unable to be used. It accumulates enhance mitochondrial energy pro-

4 In Focus: Friedreich’s Ataxia ©2010 MDA duction by rendering free radicals Precision in iron chelation therapy is which is essential for the synthesis harmless. crucial. of iron-sulfur clusters and heme,” Richardson says. Coenzyme Q10, vitamin E and ide- “You have to be very careful — you’re benone were among the first anti- on the knife’s edge,” Richardson The role for iron chelation as a treat- oxidant compounds to be tested in explains. “You have to give an ment for FA is thus limited. FA after the frataxin gene discovery. appropriate dose that potentially will These studies, particularly of idebe- remove the iron from the mitochon- Results from an ongoing clinical trial none, continue today. A long history dria without causing whole-body iron with study sites in Belgium, France, of clinical trials of the drug has pro- depletion.” Italy and Spain may increase under- duced some intriguing results. (See standing of how iron chelation may Idebenone on Trial, page 9.) Although Richardson’s team has (or may not) fit into an FA therapy demonstrated that iron chelation can regimen. Idebenone (under the brand name improve symptoms in a mouse with Catena) is not approved for use an FA-like disease, in the end the The study aims to assess the tolera- in the United States. It did receive animal still gets ill and suffers from bility and safety of the iron chelation conditional market approval for FA heart problems. drug deferiprone in people with FA. treatment in Canada in July 2008. In development by the pharmaceuti-

Around that same time, however, it “This is because — despite remov- cal company ApoPharma, headquar- = Mitochondrion failed to obtain marketing approval ing the toxic iron — we couldn’t tered in Canada, the drug has been = Frataxin in Europe, where its trade name is replace the function of the frataxin, licensed for treatment in Europe and = Nucleus Sovrima. = Iron Normal Cell Although antioxidants alone can’t = Chelator cure FA, this class of drug may pro- vide some benefit, alone or in combi- = Mitochondrion nation, with other therapies. = Frataxin FA treatment strategy: Iron = Nucleus chelation FA-affected cell = Iron Des Richardson and colleagues have done extensive work on iron = Chelator chelation, a therapeutic strategy that aims to target toxic mitochondrial iron and remove it via compounds FA-affected cell after called iron chelators. mitochondrial iron chelation treatment In July 2008, Richardson’s team published study results showing that treatment with iron chelation significantly decreased iron levels in the heart, and limited the harmful increase in the size of the cardiac muscle (a condition called myocar- dial hypertrophy) in mice that don’t express frataxin in the heart. (For more about this study, see Research In FA, a deficiency of the frataxin protein changes the way the body regulates iron levels, leading to toxic levels of Updates in the December 2008 iron in the cellular “energy factors” called mitochondria. Chelators designed to penetrate the mitochondria target the Quest.) iron accumulation and remove it.

5 In Focus: Friedreich’s Ataxia ©2010 MDA Asia of the iron-loading disorder thal- with end-stage kidney disease who extended treatment phase. Results assemia. were being treated with EPO, and included significant clinical improve- found a significant increase in frataxin ment based on measurements from “I’m cautious but hopeful that iron production in those patients within 48 two different ataxia rating scales, with chelators might be used to reduce hours of treatment. changes in locomotion and speech the amount of toxic mitochondrial contributing the most to overall score iron, but again it will not fix the prob- In 2010, another Austrian research improvement. Parameters indicative lem — that is the lack of frataxin,” team (including some of the same of oxidative stress also were mark- Richardson says. researchers from the 2005 study) edly reduced after treatment. reported results of a small “proof-of- “Eventually we have to generate a concept” trial in which 12 people with Finally, building on their earlier stud- technology that will restore or replace FA received EPO injections three ies, several members of the Austrian frataxin function, and that’s really the times a week for eight weeks. group, with colleagues, showed that a ‘Holy Grail.’” derivative of EPO called carbamylat- Eight of the 10 trial participants ed erythropoietin (CEPO) increases FA treatment strategy: exhibited a stable increase of frataxin frataxin levels in FA-affected cells, Erythropoietin levels over the study period, with indi- but does not, as EPO does, stimulate vidual increases ranging from 15 to increased blood-cell production. This 63 percent. makes it a potential alternative for Erythropoietin, or EPO, is a sugar- treatment of FA. coated protein, or glycoprotein, Ataxia severity, as measured by secreted by the kidneys. the assessment and rating of ataxia FA treatment strategy: HDAC (SARA) scale, showed a 6 percent inhibitors In addition to its neuro- and cardio- improvement in study participants, protective properties, EPO: and measures of oxidative stress Using a class of drugs called histone were significantly reduced. deacetylase (HDAC) inhibitors, scien- • stimulates production of red tists hope to “turn back on” the fratax- blood cells; In an open-label follow-up study, in gene, allowing cellular machinery • works as a powerful growth factor eight of the 10 participants from to read its genetic instructions and that can increase cell size and the first trial underwent a six-month produce the frataxin protein. numbers of mitochondria; and Chromosomes are located in Two Types of Epigenetic Modification Methyl groups attach to DNA, • increases frataxin protein the cell nucleus and are made production through an as-yet- compacting it and preventing up of a long DNA molecule and its code from being read or undetermined mechanism. its associated proteins. They made into proteins. carry hereditary information. Limitations to prolonged EPO treatment include harmful side effects such as increased blood-cell produc- Methyl group DNA tion and the risk of tumor growth. DNA Methyl group In 2005, a group of Austrian investi- Chromatin gators targeted human erythropoietin Chromosome to cultured lymphocytes (a type of Chromatin is the combination of DNA and pro- white blood cell) taken from people teins, some of which are known as “histones.” with FA, and found the cells sig- A number of chemical “flags,” including methyl nificantly increased production of and acetyl groups, can attach to the histones and frataxin protein. control whether it is expanded or compacted. Gene silencing can be the result of “epigenetic” control. In the case of FA, chemical flags called acetyl groups, which The researchers also studied people signal to the cell that the gene is open and ready for its protein-making instructions to be read, are lost. HDACs pre- vent the loss of these flags, essentially maintaining the gene’s “active” status.

6 In Focus: Friedreich’s Ataxia ©2010 MDA produce the frataxin protein. interest, Gottesfeld says, and in April In December 2009, MDA awarded Early attempts with a synthetic small 2007, Repligen Corp. of Waltham, a new grant to the company totaling molecule reversed the deleterious Mass., entered into a commercial $731,534, to support the ongoing effects of the GAA repeat expansion license with Scripps for exclusive development of RG2833, including and turned the frataxin gene back rights to further develop the com- completion of the preclinical testing on to a small extent in cell culture pound. required to move the experimental studies. In further testing, however, drug toward human clinical trials. in Massimo Pandolfo’s mouse model “Repligen made Scripps the best for FA, it was found that the molecule offer — not just financially, but in Repligen has filed an Investigational didn’t get into the brain. terms of our confidence in them sin- New Drug application with the U.S. cerely wanting to take this forward,” Food and Drug Administration (FDA) “That got me thinking that the mecha- Gottesfeld says. for a phase 1 study of RG2833. nism of gene silencing may have Pending approval by the FDA, the something to do with chromatin and “That’s even more important than the study, which will enroll up to 40 epigenetics,” says Joel Gottesfeld, dollars that the company may pay to healthy volunteers without FA, will professor in the department of molec- Scripps for the rights, because it’s of evaluate the safety and pharma- ular biology at Scripps Research no use unless the company really is cokinetic profile (the way the drug Institute in La Jolla, Calif. dedicated to do the work.” behaves in the body) of the compound. “And that led me to propose that James Rusche, Repligen senior vice molecules that could revert inactive president of research and develop- Researchers also will evaluate bio- chromatin to active chromatin might ment, says, “We are really excited chemical indicators called biomarkers be of benefit.” about this approach. It’s not treating a in the participants’ blood as a means symptom — it actually treats the fun- of measuring RG2833’s activity. Gottesfeld’s lab began a search for damental basis of the disease.” HDAC inhibitors that could turn the This study will be the first step in the frataxin gene back on, and found one, Repligen has since synthesized hun- clinical development of RG2833 as a a molecule called BML210. A chemist dreds of derivatives of 106, one of potential treatment for FA. in the lab synthesized a collection of which, RG2833, has been designated derivatives of the compound, eventu- for clinical development. The FDA has granted RG2833 ally leading up to a molecule called orphan drug designation, which may 106. Studies have confirmed that RG2833 qualify Repligen to receive seven is most potent against HDAC3, an years of market exclusivity in the The 106 molecule was passed on to enzyme that, when blocked, increas- United States, provided that it is the Pandolfo’s lab, where it was shown es frataxin production. first company to receive approval for that it does activate the frataxin gene RG2833 for FA. in both the brain and heart of their “We think this is a sound and exciting FA mouse model, and subsequently opportunity to develop a treatment for Combining the use of different leads to increased protein levels. FA,” Rusche says. “Small molecule treatment strategies is likely, says drug development for a neurodegen- Gottesfeld. After a number of preliminary experi- erative disease is difficult, but with ments to show the molecule wasn’t support from academic and patient “A treatment for Friedreich’s ataxia toxic even in prolonged treatment sit- advocacy groups we feel Friedreich’s may turn out to be a combination of uations, Gottesfeld and Scripps filed ataxia is the right place to try.” treating symptoms with either an iron a provisional patent application and chelator and/or an antioxidant, plus began looking for a commercial part- MDA provided Repligen with two boosting levels of frataxin protein — ner to help move the drug forward. grants to fund the early stages of the either by protein replacement or by RG2833 program. The first, awarded our means, turning the gene back A number of companies expressed in late 2007, totaled nearly $1 million. on.”

7 In Focus: Friedreich’s Ataxia ©2010 MDA FA treatment strategy: A 2007 study analyzed the fea- (For an interview with R. Mark Payne Gene therapy sibility of gene insertion via the about heart problems in FA, see emptied-out shell of the herpes Treating the FA-Affected Heart, page Various gene therapy-based simplex virus type 1 (HSV-1), part- 18.) strategies also hold the potential nered with a stretch of DNA called to benefit individuals with FA. an amplicon that helps the vector Where are we now? Although it’s relatively early in the target a specific cell type. game, a limited number of stud- The FA disease process is ies in mice and human cells have Results in FA-affected mice and extremely complex. Scientists still yielded some encouraging results. human cells showed highly effi- are refining their knowledge of its cient DNA transfer and increased causes and effects, but a great In a 2005 study, researchers used levels of frataxin production. deal of progress has been made. lentiviral or adeno-associated viral Still, more needs to be done. (AAV) vectors to carry the human Similar positive results in 2007 frataxin gene into fibroblasts (cells came from a Spanish study in It’s becoming clear that in addition that mature into a variety of con- which mice were engineered so to mitochondrial consequences, nective tissue types) from FA that researchers could eliminate, there are other far-ranging cel- patients. (A vector is a delivery or “knock out,” frataxin activity lular consequences. A number of vehicle for therapeutic genes.) specifically in motor neurons. pathways that are normally active in cells are lost in the absence of Results included increased frataxin The mice developed neurologi- frataxin and their loss then con- protein levels and a reduction in cal symptoms after four weeks, tributes to the progression of FA the treated cells’ sensitivity to oxi- but achieved full recovery in as symptoms, Grazia Isaya notes. dative stress. few as four weeks after receiving injections of HSV-1 amplicon vec- “This may explain why single tors carrying DNA that codes for drugs like antioxidants or iron human frataxin. chelators alone cannot be entirely successful in terms of improving A Spanish study published in 2010 the disease in patients. describes the successful use of artificial chromosomes and similar “Perhaps only by increasing the constructs called episomes to act levels of frataxin can one ultimate- as vectors for transporting genes ly treat the disease.” to their targets. To see a listing of current and R. Mark Payne, a professor of completed clinical trials in FA, go pediatrics and a pediatric cardi- to www.clinicaltrials.gov and enter ologist at the Indiana University “Friedreich’s ataxia” in the search School of Medicine in Indianapolis, box. is working on gene replacement therapy for FA.

His strategy involves using a construct called TAT-frataxin fusion proteins as a mechanism for replacing the missing FA gene product.

Overall, idebenone has been shown to be safe and well-tolerated in a number of phase 1, 2 and 3 human clinical trials dating back to 1999. The most common side effects are mild to moderate gastrointestinal issues such as diarrhea, nausea and indigestion. Early trials at low doses first demonstrated the potential for idebenone to reduce FA-associated cardiomyopathy (heart muscle abnormality). Over the past decade, the drug has consistently demonstrated in a number of trials its ability to improve heart structure by reducing FA- related abnormal thickening (cardiac hypertrophy) of tissues in particular areas of the heart. Specific measurements used to determine such improvement include interventricular septal wall thickness (SWT), left ventricular posterior wall thickness (PWT) and left ventricular mass index (LVMI). In addition, results from some trials have suggested a reduction in cardiac strain, as indicated by a measurement called shortening fraction, which measures performance of the heart by assessing the change in diameter of the left ventricle between the contracted and relaxed states. The decrease in cardiac strain was associated with improved heart function. A number of studies found that cardiac benefits varied significantly among individuals. Most indications in earlier trials of idebenone’s potential to improve or stabilize neurological dysfunction found no benefit. More recent trials, however, particularly those in which higher doses of the drug have been tested, have demonstrated improved neurological function.

• ADL: Activities of Daily Living. This ratings system assesses the ability of an individual to perform day-to-day activities such as dressing, eating, moving, toileting, taking medication, using a telephone or other technology, and others. • CAGRS: Cooperative Ataxia Group Rating Scale. This scale measures neurological function/dysfunction. • FARS: Friedreich’s Ataxia Rating Scale. Another measurement of neurological function/dysfunction. • ICARS: International Cooperative Ataxia Rating Scale. This measurement of neurological function/dysfunction currently is the preferred scale. • Catena/Sovrima: Catena is the brand name for idebenone in Canada and the United States. Sovrima is the brand name for the drug in Europe.

Date, Location, Trial Trial Objective & Description Trial Results

2010 Aims of this study included evaluation of No significant differences were observed in the effects of combined idebenone-defer- total ICARS scores when comparing status at Spain iprone therapy on neurological signs and the beginning of the study (baseline) and the end of the study in the whole group of patients. heart function. However, differences were noted in specific Combined Therapy with Idebenone and ICARS categories. Namely, posture and gait Deferiprone in Patients with Friedreich’s Twenty individuals with FA were treated scores worsened, while fine-motor function Ataxia with idebenone (20 mg/kg/day) and the improved significantly. iron chelator deferiprone (20 mg/kg/day) Heart-imaging (echocardiography) data for 11 months. showed a significant reduction in abnormal thickness of a part of the heart called the septum.

MRI testing showed statistically significant reduction, between baseline and after 11 months of therapy, of iron deposits in a part of the brain called the dentate nucleus.

Results suggest combined idebenone- deferiprone therapy in people with FA confers an overall stabilizing effect in neurological dysfunction, and significant improvement in heart hypertrophy (abnormal enlargement) and iron levels in the brain.

The therapy was well-tolerated with mild side effects. Noted risks include neutropenia (an abnormal decrease in levels of a particular type of white blood cell) and reduction of blood iron levels.

Date, Location, Trial Trial Objective & Description Trial Results

2010 This study was designed to evaluate the The MICONOS trial missed its primary endpoint, safety and efficacy of three different doses which was mean change in ICARS score as measured at the beginning, and again at the end, of the Europe of Catena/Sovrima versus that of placebo. study. No significant difference was noted between those receiving idebenone and those receiving Mitochondrial Protection with Idebenone A total of 232 individuals (primarily adults) placebo. in Cardiac or Neurological Outcome Study with FA received the low (180/360, In addition, no difference was noted between the (MICONOS) depending on body weight, mg/day), active and placebo groups in measurements of key medium (450/900 mg/day) or high dose anatomical and functional cardiac parameters. (1,350/2,250 mg/day), or placebo, every Data still is being culled from long-term extension day for 12 months. studies following this trial. The MICONOS extension was listed as “ongoing, but not recruiting patients” as of Aug. 20, 2010 on Clinicaltrials.gov. 2010 This phase 3 observational study ex- Patients were assessed using the Pediatric Quality amined the effect of intermediate-dose of Life Inventory, the ICARS, and an Activities of Daily Living Scale, both before starting idebenone Canada idebenone (20 mg/kg/day) on quality of life and after one year of therapy. and neurologic function measures. Intermediate-Dose Idebenone and Quality Physical scores on the Pediatric Quality of Life Inventory were universally worse after one year, and of Life in Friedreich’s Ataxia Seven patients with FA, ages 13 years correlated with decreased activities of daily living to 18 years (four male and three female) scores. were administered treatment for a period Despite worsening physical scores, there was a of one year. trend toward improved total, emotional, social and school components of quality of life scores.

There was no statistically significant change in Pediatric Quality of Life Inventory scores from the beginning to the end of the study.

Functional ability, as measured by activities of daily living scores, appeared to have the most influence on the perception of physical quality of life. 2009 This phase 3 study compared the safety, The IONIA study missed its primary outcome mea- tolerability and efficacy, of two different sure, which was the mean change in ICARS scores taken at baseline and again after 24 weeks. United States doses of Catena versus placebo. The low dose was 450 or 900 mg/day, depend- Patients who received idebenone improved by 2.5 Idebenone Effects on Neurological ICARS ing on body weight. The high dose was points on mean ICARS score compared with baseline, while patients in the placebo group improved Assessments study (IONIA) 1,350/2,250 mg/day. by 1.3 points. Patients who took idebenone also improved by 1.6 points on the FARS, while patients Seventy individuals with FA, ages 8 years taking placebo declined by 0.6 points. through 18 years, who still were ambu- For both end points, the difference between the latory, were assigned to one of three idebenone and placebo groups was not statistically treatment groups: low-dose idebenone, significant. high-dose idebenone or placebo. Doses (It should be noted that the IONIA study was were administered daily over a period of designed using parameters from the prior U.S. six months. phase 2 NICOSIA study. Compared to the placebo group, improvement in both IONIA groups taking Catena measured only about half as much as had those in the prior U.S. Phase 2 NICOSIA study. It was observed that those in the IONIA placebo group did not deteriorate to the extent expected from the NICOSIA study or as described in literature, possibly skewing the results.)

Date, Location, Trial Trial Objective & Description Trial Results

2009 This study was a retrospective analysis The heart’s responsiveness to treatment with of 35 individuals with FA (20 with cardiac idebenone varied greatly among trial participants. The researchers observed no correlation with sex, Italy hypertrophy, 15 without), who were treated age, size of GAA repeat expansion, or severity of with idebenone 5 mg/kg/day for up to 60 cardiomyopathy prior to the study. Low-Dose Idebenone Treatment in months. In those who had cardiac hypertrophy at the Friedreich’s Ataxia with and without beginning of the study, no changes in heart tissue Cardiac Hypertrophy thickness measurements were noted. In those who began the study without cardiac hypertrophy, measurements showed the thickening of particular areas of heart tissue consistent with cardiac hypertrophy.

No neurological benefits were noted. There was significant progression of neurological dysfunction over the time period studied. 2008 This phase 2 study aimed to establish Results showed that idebenone was safe and safety data and effect on neurological well-tolerated, and that it produced a positive Switzerland symptoms of high-dose idebenone in effect as measured by ICARS as well as with activities of daily living scales. United States young individuals with FA. Analysis revealed that those treated with the NIH Collaboration with Santhera in Ataxia The trial enrolled 48 people with FA, with drug showed a trend toward dose-proportional (NICOSIA) trial 12 in each of three dose groups, and 12 in improvement in neurological function, as a placebo group. measured by ICARS, after a six-month course of treatment. 2008 The aim of this study was to assess the Neurological status was evaluated using effectiveness of long-term treatment with ICARS, and heart health was tested using a Spain idebenone in people with FA. type of heart-imaging test called an echocardiogram.

Idebenone Treatment in Pediatric and Ten children with FA (ages 8 years to 18 ICARS scores showed initial improvement in Adult Patients with Friedreich’s Ataxia: years) and 14 adults (ages 18 years to 46 children, with stabilization over the long term. Long-Term Follow-Up years) with genetic diagnosis of FA were In adults, scores showed significant worsening treated with idebenone (5-20 mg/kg/day) of neurological function. for a period of three years to five years. Analysis also showed the treatment prevented progression of cardiomyopathy in both children and adult patients.

The authors suggested that, based on these results, effectiveness of idebenone therapy may depend on the age at which it’s initiated. 2007 This trial enrolled 48 people with FA be- Treatment with doses of idebenone was gener- tween the ages of 9 years and 17 years. ally well tolerated at all doses up to 2,250 mg/ United States day. At higher doses the treatment was associated with a trend toward improvement (but not Each was randomly placed into a placebo a significant difference) in neurological function Neurological Effects of High-Dose Ideben- or one of three idebenone treatment and activities of daily living in patients with FA. one in Patients with Friedreich’s Ataxia: groups. Those in the treatment groups The degree of improvement correlated with A Randomized, Placebo-Controlled Trial received fixed daily doses of idebenone, the dose of idebenone, suggesting that higher (180/360 mg/day, 450/900 mg/day or doses may be necessary to have a beneficial effect on neurological function. 1,350/2,250 mg/day, depending on body weight) over a period of six months. Overall, analysis showed no significant difference in FARS, ICARS or ADL scores. In one experiment, however, in which patients who required wheelchair assistance were excluded, a significant improvement in ICARS scores and apparent dose-related response in ICARS, FARS and ADL scores was observed.

Date, Location, Trial Trial Objective & Description Trial Results

2007 Researchers followed 104 people with The neurological condition of FA patients deteriorated slowly over time, even with idebenone FA every six months over a period treatment. It was suggested that overall progression France averaging five years, using a standard- may have been underestimated ICARS scores, ized measurement protocol. which plateaued in those patients with long disease Neurological, Cardiological and Oculo- courses. Although cardiac hypertrophy decreased under treatment, cardiac function did not improve. motor Progression in 104 Patients with No trial participants were receiving an- Friedreich’s Ataxia During Long-Term Specifically, ICARS scores worsened during follow- Follow-Up tioxidant therapy prior to the beginning up, regardless of whether the patients received ide- of the study. Eighty-eight were treated benone. Worsening of the ICARS scores increased faster in patients with onset before age 15 years with idebenone at 5 mg/kg per day; 16 compared with the others. declined the treatment. Oculomotor (eye movement) function deteriorated slightly. 2006 The goal of this study was to examine Overall ICARS scores did not improve, but neurological effects of idebenone. Investi- improvements in neurological function were France gators also looked at the drug’s effect on seen in speech, increased hand dexterity and decreased fatigue. blood levels of malondiadehyde (MDA), Expanding View of Phenotype and Oxida- an organic compound known to indicate Treatment with idebenone was positively corre- tive Stress in Friedreich’s Ataxia Patients oxidative stress. lated with an increase in blood levels of MDA. with and without Idebenone Twenty adults with FA were treated with 5 mg/kg/day to 10 mg/kg/day idebenone over periods varying from several months up to three and a half years. 2003 Researchers studied eight people with FA, Evaluations of ataxia, cardiac structure and between the ages of 9 years and 27 years, function, biochemical markers and adverse Belgium with cardiomyopathy. effects were conducted at the beginning of the study and after four, eight and 12 months of treatment. Idebenone Treatment in Friedreich’s All trial participants received 5 mg/kg/day Ataxia: Neurological, Cardiac and Bio- in three doses (maximum 300 mg/day) for As indicated by CAGRS scores, idebenone did chemical Monitoring one year. not halt the progression of ataxia. At the end of therapy, cardiac ultrasound demonstrated significant reduction of cardiac hypertrophy in six of eight patients. Analysis showed this reduction of hypertrophy was preceded by an early and linear improvement in cardiac function. 2003 The goal of this trial was to determine car- No serious side effects were associated with diac and neurological effects of idebenone idebenone treatment. Italy in people with FA. Effects of idebenone on the heart varied greatly among the trial participants. Idebenone Treatment in Friedreich Twenty-nine study participants with FA, Patients: One-Year-Long Randomized ages 21 years to 32 years, were placed Analysis revealed significant reductions in Placebo-Controlled Trial into idebenone and placebo groups (14 measurements indicative of cardiac hyper- and 15, respectively. Each received either trophy in the treatment group; these results were not observed in the placebo group. No idebenone (5 mg/kg/day) or placebo three improvement was noted in various other heart times daily. ultrasound measures or in neurologic condition.

Date, Location, Trial Trial Objective & Description Trial Results

2002 The aim of this trial was to assess the After six months of treatment, cardiac ultrasound indicated a reduction in parameters indicative of efficiency of idebenone on cardiac cardiac hypertrophy in approximately half of the France hypertrophy in FA. trial participants. Cardiac hypertrophy was largely stabilized in the other half and in none of them did Idebenone and Reduced Cardiac the hypertrophy significantly increase over the six- Idebenone was given orally (5 mg/kg/ month trial period. Hypertrophy in Friedreich’s Ataxia day) to 38 trial participants with FA, No correlation was found between responsiveness ages 4 years to 22 years (20 males, 18 to idebenone and age, sex, initial ultrasound indices, females). or the number of GAA repeats in the frataxin gene. 2002 The aim of this study was to assess the No changes were noted in cardiac measure- effects of idebenone treatment in cardiac ments taken prior to and after the study. Spain health and neurological function in people Concentrations of idebenone in trial par- with FA. ticipants’ blood showed significant positive Friedreich’s Ataxia: Idebenone Treatment correlation with ICARS scores before and 12 in Early-Stage Patients Nine trial participants with FA, ages 11 months after the start of the study. years to 19 years, were treated with idebenone (5 mg/kg/day) for one year. Significant improvement was observed in ICARS scores measured three months after start of treatment.

Notable improvement in part of the brain called the cerebellum (responsible for motor function and balance) was observed in patients with mild cases of the disease after three months of therapy. Treatment at early stages appeared to reduce cerebellar degeneration. 2001 In this study, researchers examined effects MRI results showed impairment in skeletal of idebenone on cardiac function. muscle of all FA patients, which idebenone did Germany not help. No positive benefits were noted, and heart imaging tests (echocardiograms) failed Nine FA patients, ages 9 years to 54 to confirm results from a preliminary study Idebenone in Patients with Friedreich’s years, received either 360 mg/kg/day of suggesting improvement of FA-associated Ataxia idebenone or placebo for a period of one cardiomyopathy with idebenone. and a half months. The study authors noted that the duration of treatment probably was too short to make a valid conclusion. 2000 The aim of this study was to determine The small molecule biomarker, 80H2’dG the effects of idebenone on a particular 8-hydroxy-2’ –deoxyguanosine, measured in Germany biochemical indicator “biomarker” for urine output, decreased by 20 percent with idebenone treatment — a possible indicator of United States oxidative stress. reduced oxidative stress.

Oxidative Stress in Patients with Eight people with FA were treated with Friedreich’s Ataxia idebenone (5 mg/kg/day) for a period of two months. 1999 Three individuals, ages 11 years, 19 years Results showed a reduction of abnormal and 21 years, received 5 mg/kg/day of ide- thickening in measurements of three areas of France benone for a period of four to nine months. the heart. Note: One individual who continued the treat- Effect of Idebenone on Cardiomyopathy in ment for five years exhibited decreased cardiac Friedreich’s Ataxia: A Preliminary Study hypertrophy.

Susan Perlman, M.D., director of some of them, the symptoms are besides a heart muscle that gets the Ataxia Clinic, Department of relatively mild. They may notice too thick or too thin, is a heart Neurology, University of California- palpitations, they may feel a little muscle that becomes stiff. It’s not Los Angeles, is a neurologist short of breath when they’re exer- all stretched out and flabby, and who’s been doing research in, and cising, and ultimately the workup it’s not particularly thick. It just taking care of individuals with, will show, Yes, you have cardio- becomes stiff. There’s probably Friedreich’s ataxia (FA) for some myopathy, and it’s related to your scar tissue or fibrous tissue build- 30 years. In November 2010, she Friedreich’s. ing up between the heart muscle sat down to talk with Margaret fibers. On an echocardiogram, Wahl, MDA’s medical and science There is often thickening of the the heart size may look relatively editor. heart muscle, called “hypertrophic” normal, but it can’t function well cardiomyopathy, especially on the because it’s stiff. Q: What are some of the treat- left side of the heart. Sometimes able aspects of Friedreich’s it can get to the point where the Normal cardiac function can usu- ataxia? muscle is so thick that blood has ally be maintained into a patient’s trouble flowing out of the heart. 20s, requiring no medication. A: First of all, everything is treat- That’s known as “outflow obstruc- Some people will require medica- able. Any symptom somebody tion.” More often, the heart muscle tion earlier. has, there is something that is just gets thick, which makes it hard available right now that can be for it to pump blood efficiently. Small studies suggest that an used to make things milder and abnormality in heart thickness is improve functional ability and qual- In some cases, the heart muscle is the first thing that’s picked up in ity of life. so damaged by the frataxin protein youngsters and that it may or may deficiency caused by Friedreich’s not cause symptoms; but that as Q: What about the cardiac ataxia that it can actually thin out they get older, they may develop problems in FA? and stretch like a flabby rubber palpitations, fatigue and short- band. That also makes it harder ness of breath. In their 20s, some A: There are probably symptoms for the heart to pump the blood Friedreich’s patients may begin to of cardiomyopathy [heart muscle out. lose heart function, so that, instead abnormality] in more than half of the heart pumping the normal the people with Friedreich’s. In Another thing that we’ve noticed, 60 percent or so of the blood out

14 In Focus: Friedreich’s Ataxia ©2010 MDA 60 percent or so of the blood out the motor pathways. Some parts of the nervous sys- with each contraction, it’s pumping tem, such as the thinking and maybe 30 percent. In the central nervous system [the emotion-experiencing parts of the brain and spinal cord], it’s the brain, appear to have more energy The kinds of medications that are long nerve tracts that are the most reserves and to tolerate energy used that can help preserve heart affected. These normally convey deficiency better than the motor function are called beta blockers information through the spinal cord and sensory fibers. [examples are propranolol and to the brain, particularly the cere- metoprolol] and ACE inhibitors bellum, the movement coordination The cerebellum, where move- [examples are captopril and enalo- center; and from the brain down ments are coordinated, has a very pril]. the spinal cord to the peripheral low safety factor. It doesn’t store a nerves and muscles. lot of energy, so if energy produc- These drugs take some of the load tion goes down, areas within the off the heart muscle so that it’s not Also involved is the peripheral cerebellum itself will ultimately working as hard. They’re becom- nervous system, the nerve fibers show some stress and atrophy ing standard care among many outside the spinal cord that send [shrinkage]. cardiologists who see people with signals to the muscles and relay Friedreich’s ataxia. information from the periphery of The weakness that patients with the body back to the spinal cord Friedreich’s ataxia experience is We’ve seen individuals with and brain. not because the muscle is being Friedreich’s and measurable directly damaged, with the excep- thickening of the heart who have tion of the heart muscle. Skeletal started the antioxidant idebenone, muscle is an innocent bystander and a year later, their heart is that experiences the consequenc- back to normal. These are just es of its peripheral nerve connec- single patient observations, but tions weakening. [When signals both idebenone and the related from motor nerves fail to reach supplement coenzyme Q10 seem muscle, the muscle can’t contract.] to reverse some of the thickening of the heart. We don’t have all the The sensory loss and loss of coor- data yet. But I recommend starting dination are often more of a prob- either coenzyme Q10 or ideben- lem than the weakness. The very one, the earlier the better, while first symptoms in the average per- research continues. son with Friedreich’s are problems The longer the nerve fiber, the with balance, clumsiness, and Some individuals with more more energy it needs to transport trouble running without tripping, advanced heart problems may substances. So it’s the spinal long rather than overt weakness. require pacemakers or implanted tracts and the long peripheral defibrillators to reduce the risk nerve fibers that are targeted pri- The nerve fibers that bring signals of the heart going into a severe marily in Friedreich’s. Symptoms from the joints about the position rhythm problem that could cause come up initially in the legs and of the limbs are also undergoing the heart to stop. then, after a few years, will be damage. If you lose the sense of noticed in the arms. The path- where your foot is, where your leg Q: Are the pathways related to both ways are a little shorter going is, because you don’t have joint sensation and movement — the to the arms and can resist the position sense, it will be extremely sensory and motor pathways — stress of deficient frataxin and low difficult to control signals that involved in FA? energy production a little longer. you’re sending to move the leg. Ultimately, there will be changes in When we see a teenager with A: Yes. There are two aspects speech and possibly swallowing, Friedreich’s who all of a sudden here, the sensory pathways and vision or hearing. is having a lot more difficulty with

15 In Focus: Friedreich’s Ataxia ©2010 MDA is having a lot more difficulty with they’re sitting in a wheelchair and and so forth. We encourage patients walking and balance, it’s usually not are below eye level. These are ter- who are having functional problems because of weakness. It’s usually rible assumptions and behaviors in with vision to work with the Braille because of the progression of the society that we have to change. Institute. (The Braille Institute at sensory changes to the cerebellum www.brailleinstitute.org and (800) and the flawed output from the cer- Q: Does speech therapy help? 272-4553 offers many resources for ebellum, which are causing balance people with poor vision.) difficulties. A: Speech therapy helps, and we usually recommend it. Usually, the Q: A relatively rare problem in Q: Is physical therapy helpful in younger patients, if they speak slow- FA is diabetes. It’s connection to FA? ly, can develop reasonable breath FA seems somewhat mysterious. control and make their speech intel- Can you help us understand it? A: Exercise, whether it’s for muscle ligible. Some older patients may conditioning, strengthening or decide to use speech-generating A: It is mysterious. People with stretching, or whether it’s coordina- devices. Friedreich’s ataxia can develop tion-based exercise, is extremely dysfunction of the beta cells in the important. Q: What about hearing and pancreas that normally produce vision in FA? insulin. Why the pancreas? We don’t If patients with ataxia engage in a know, but there’s something about regular program that includes coor- A: In young people with this pathway that is affected by the dination and balance exercise, they Friedreich’s, before the age of 25, Friedreich’s ataxia gene mutation. seem to be able to turn the clock it’s unusual to see noticeable vision Besides altered insulin production, back on their symptoms. The dis- or hearing problems. If we did very the body’s tissues may not respond ease will continue to progress, but sensitive hearing or vision testing, as well to insulin as they normally at least you can bring people up a called evoked potential testing, we would. notch or two and then level them out would probably see very mild chang- for a period of time. We’ve seen this es. It wouldn’t affect their ability to Twenty percent of people with over and over again. read or see, and it wouldn’t affect Friedreich’s ataxia have a condition their ability to hear. called carbohydrate intolerance, So we encourage all of our ataxia which is an inability of the body to patients, especially Friedreich’s atax- But as the disease slowly progress- completely process carbohydrates — ia patients, to get involved with regu- es, many people with Friedreich’s sugars and starches — into energy. lar daily exercise, which includes will develop high-frequency hearing appropriate balance and coordina- loss, meaning there is hearing loss Ten percent of Friedreich’s patients tion training and core exercise. at the higher pitches, such as the actually develop insulin-requiring Depending on what their limitations speech pitches. They have trouble diabetes. are, they also can do some muscle picking out a conversation in a noisy conditioning, strengthening and room. It can often be compensated It’s not as common as some of the stretching. We recommend that a for with the same measures you other features of Friedreich’s ataxia, patient work with a physical therapist would use for anybody with hearing but it’s something that we screen and do a home exercise program. loss, such as hearing aids. all our patients for every year until they’re in their 20s. Once they hit Q: Among the most troubling Vision loss is more subtle and gener- 25, it’s less likely that they’ll develop symptoms in FA is the difficulty ally not as disabling, at least early diabetes related to Friedreich’s, with speech, because it can make on, as the hearing changes. For although they’re not immune to it other people think the person with the most part, we recommend that from other causes. FA isn’t intelligent. Can you com- people do all the things that people ment on that? do who are visually impaired for other reasons, such as using large- A: Exactly. That, and the fact that print materials, magnifying devices

16 In Focus: Friedreich’s Ataxia ©2010 MDA Q: Do you recommend dietary My impression is that the primary restrictions? cause of death is the heart problem. And now that the heart problems can A: Most youngsters with be managed better, I think people Friedreich’s who develop diabetes can expect to live a much longer life. are going to require insulin. If you’re They might be living it in a wheel- an insulin-dependent diabetic, you chair, but from that wheelchair, they have to know what you’re taking in can work on a computer, speak to so you can plan your insulin regi- people, get out and so forth. I have men. patients with Friedreich’s who are in their 50s, 60s and 70s. Many If they don’t have full-blown diabetes have completed college, worked in but have carbohydrate intolerance, interesting fields, had families and then I think it’s important to restrict done whatever they could to support the amount of free sugar they take research in Friedreich’s ataxia. in. Complex carbohydrates, which are starches and fiber, are appropriate, as is a certain amount of fat and protein. So it’s basically a diabetic diet. You don’t have to completely eliminate carbs. Consultation with a nutritionist in planning an appropriate diet is recommended.

Q: It’s often said that Friedreich’s does not cause any cognitive impairment. Has that been your observation?

A: That has been my observation. However, I do think there is a greater risk of depression. You have to be alert and not fail to recognize depression, even if it’s unrelated to Friedreich’s. It’s something that is treatable with medication and coun- seling.

Q: Is life span affected?

A: One thing that our patients are still telling us is that when they receive their diagnosis of Friedreich’s, the doctor may tell them they can’t expect to live much past the age of 30. That clearly is not the case anymore.

17 In Focus: Friedreich’s Ataxia ©2010 MDA R. Mark Payne, M.D., professor of child who’s been athletic, running ataxia diagnosis between the ages pediatrics at Riley Heart Research and playing, begins to become of 10 and 18. At that time, they Center, Indiana University, is a more clumsy or lose his or her frequently have a thick heart that pediatric cardiologist whose medi- coordination. The parents eventu- functions fine. Then, over time, that cal specialty is intervention in chil- ally become alarmed and ultimately thick heart begins to function worse dren with heart disease, and who take the child to a neurologist, who and worse. In about 10 to 15 years, conducts research on heart disease may or may not refer them to a they can develop severe heart fail- due to mitochondrial defects. cardiologist, because it isn’t always ure from this. known that the heart is involved. In Friedreich’s ataxia (FA), heart Q: What are the heart symptoms problems are related to a deficiency In reality, any patient who has a that patients experience? of the frataxin protein, which is nor- diagnosis of Friedreich’s ataxia who mally located in the mitochondria. hasn’t seen a cardiologist needs to A: They may have irregular heart get to one pretty quick. rhythms, which they can feel as pal- Q: Are the cardiac problems in pitations, as the heart beats faster FA somewhat under-recognized? Q: What kind of cardiomyopa- or is irregular. It’s not really painful, thy [heart muscle abnormality] but it can be uncomfortable and A: Yes. Almost all the publications do you see in FA? alarming. They may have shortness on this disease are on the neuro- of breath and difficulty breathing logic impact, but the heart disease A: The cardiomyopathy in when lying down, so they may feel is what kills people. Unfortunately, Friedreich’s is typically a hypertro- the need to be propped up when it sometimes doesn’t get much phic cardiomyopathy. That means they’re in bed. They may have attention until the patients are in the walls of the heart get really swelling of their hands and feet, severe heart failure. [Heart “failure” thick. This thickening of the heart primarily their feet, as the circulation means the heart can’t pump suf- muscle is also commonly found in becomes sluggish. ficient blood to sustain normal body mitochondrial cardiomyopathies, functions. It doesn’t mean sudden whether it’s due to Friedreich’s or Q: What’s going on in the cardiac arrest.] not. FA-affected heart?

Typically in Friedreich’s ataxia, a Patients typically get a Friedreich’s A: A particular thing about these

18 In Focus: Friedreich’s Ataxia ©2010 MDA hearts is that, over time, they FA patients get put on beta block- against which the heart has to push maintain good systolic function ers [drugs that decrease the force to pump the blood out. [contraction of the heart muscle]. and rate of heart contractions], That means their ability to pump because that’s standard therapy for Some patients will be put on digox- blood out seems to be OK — but hypertrophic cardiomyopathy. There in [a drug that increases contractile because their hearts are thick, their are no clinical trials examining the force], which may make the heart ability to relax and accept blood to use of beta blockers in Friedreich’s perform a little better. Digoxin also fill them is not OK. ataxia. helps control arrhythmias.

They develop what’s called diastolic Most patients with hypertrophic Other anti-arrhythmic drugs cardi- dysfunction [the resting phase of cardiomyopathy who don’t have ologists might use include amioda- the cardiac cycle, between contrac- Friedreich’s ataxia can still relax rone or flecainide. You have to treat tions of the heart muscle]. As a their hearts. They usually have the specific type of arrhythmia. result, they lose the ability to adapt good blood flow into the heart, to the demands of exercise or unless their hearts are really thick. Q: There’s been some evidence increased blood volume. And they don’t have stiff hearts that idebenone, an antioxidant, with a lot of scar tissue, which may help the FA-affected heart. The FA-affected hypertrophic heart may be a problem for patients with Can you comment on that? adapts to increased demands by Friedreich’s ataxia. beating faster. That’s the only way A: Yes. Small studies showed that it can adapt, since it can’t increase The average person with non- it helped thin the heart walls by a its capacity to accept more blood Friedreich’s ataxia hypertrophic small amount, with minimal, if any, with each cardiac cycle. cardiomyopathy may have a higher- improvement in cardiac function. than-average heart rate, but they If the heart keeps having to beat don’t have to increase their heart That’s not to say that idebenone faster to meet various demands, rate that much. is the wrong way to go. Idebenone that can lead to a second problem, for a lifetime may be very effective which is an irregular heart rhythm, However, if the heart has to speed at maintaining heart function. We or arrhythmia. up to accommodate the fact that don’t know until these clinical trials it can’t fill with blood, such as in are conducted. Q: How are these problems Friedreich’s ataxia, then if you slow treated? it down with a beta blocker, the But as a cure, idebenone is not it. cardiac output drops and these A: For mitochondrial cardiomy- patients will have problems. They Q: What should people with FA opathies, including Friedreich’s, feel bad and don’t have any energy. do about their heart problems? we may not have a cure, but we have multiple drugs that seem to So, I would urge cardiologists not A: The thing that I would ask help prolong life and maintain some to reach for the beta blockers as a most of all is that all patients with function, when used in combination. first-line therapy for these hearts. Friedreich’s see a cardiologist and Instead, one of the things they may that all patients with this disease In general, we treat mitochondrial want to consider is lowering blood help with clinical studies in some cardiomyopathies like Friedreich’s pressure without hurting heart perform or fashion. based on analogy to other types formance. of hypertrophic cardiomyopathies They can actually further our under- where the drugs seem to work. That can be done with drugs called standing of their disease by partici- Unfortunately, we’re not really sure ACE inhibitors, like captopril or pating in a study. Doing so may be yet what works in Friedreich’s. enalopril, which make the heart’s as simple as allowing their doctor work easier by dilating blood ves- to send their medical records to One concern I have is that many sels and lowering the pressure someone else to analyze.

19 In Focus: Friedreich’s Ataxia ©2010 MDA Anne Wallace, speech-language that push air over the vocal cords. in general has to do with cerebellar pathologist and clinical associ- You have to have respiratory mus- damage. The cerebellum is what ate professor in the Department cles working together to create air controls coordination. The cerebel- of Communication Sciences & flow to make your vocal folds work. lum controls a lot of the coordination Disorders, University of Iowa in aspects related to speech, as well Iowa City, has been at that facility In Friedreich’s ataxia, there are as to other things, such as walking. for 20 years. During that time, she’s breakdowns in the system of had a longstanding relationship speech production. There can be The earlier the onset of the disease, with the pediatric specialty clinics, varied problems that result, such the worse the problems tend to be. including the MDA clinic directed as speech that is slurred or slow or For most people with Friedreich’s, by child neurologist Katherine problems with the pitch or loudness the speech problems occur in adult- Mathews, and has worked with or rhythm of the speech. hood, and the onset is gradual. many children and young adults They don’t happen overnight. The with FA. Friedreich’s ataxia speech is typi- problems develop over time, so cally pretty slow and deliberate. The people have a chance to adapt to Q: What are the speech-related syllables are produced pretty much them. issues in FA? with equal stress on each word. For example, if I’m saying “banana Q: Can you talk about some of A: The main problem is dysarthria, peel,” I’m not saying ba-na-na-peel, the specific problems and your which means a motor speech dis- with the same stress on every syl- approaches to treating them? order, not a cognitive speech disor- lable. Someone with Friedreich’s der. Cognition is generally intact in might, however, do that. A: An average person can say so Friedreich’s ataxia. many words on a breath, and then There’s less contrast between the they automatically breathe at a cer- Dysarthria is caused by things such stressed and unstressed syllables, tain time, usually at normal phrase as muscle paralysis or weakness so it’s hard to tell, for instance, boundaries. They’ll breathe at the of the muscles related to speech whether someone is saying end of a thought or a sentence, not production or inability to coordinate “OB-ject” or “ob-JECT,” which are in the middle. these muscles. Those are the mus- two different things. cles of the lips, tongue and throat, But if all your speech is slow and also the respiratory muscles The underlying problem with ataxia because of muscle coordination

20 In Focus: Friedreich’s Ataxia ©2010 MDA problems, you still can only say so high-tech system, such as a voice many syllables per breath. If your I work with patients on trying to output device, but the more high- syllables are twice as long, you make more precise sounds, to try tech it gets, the more transporting can only say half as many things. It to make the consonants better. I the device becomes a problem. If takes the person with Friedreich’s work on words that have final con- you’re using a wheelchair, and the more breath and more work to say sonants, particularly ones that have device is connected to your wheel- something than it does the average more air pressure, what we call plo- chair, then it’s there for you, and person. For many people, that’s sive sounds, like t, d, k and g. it might be easily accessible. But frustrating. what do you do when you’re not in You have to show a person how your chair? How do you communi- Sometimes in Friedreich’s there’s they need to do that. Sometimes cate then? Do you have to always a voicing problem, where the per- you can use a tactile cue, such as be in your chair to communicate? son’s voice is coming in and out. a hand in front of their face. If you There can be a problem with a sud- were to do that, and say, “hat” with Lots of times, families that have den, really loud voice in the middle a lot of force, you can feel it on younger kids will say, “Let’s get the of a syllable. It’s related to coordi- your hand. We also use things like best kind of computer.” But here’s nation. When you make a syllable mirrors, which will fog up when you the deal: You’ve got to haul it. The louder, you actually use more air. say “hat” forcefully. These tech- child has to haul it, and maybe they When you use more air, you have niques add precision to what they have other motor problems, making even less breath for finishing the say. that prohibitive. Or maybe the bat- rest of what you’re trying to say. tery won’t hold a charge. There are What you trade off in order to be a lot of issues. They can learn to regulate these able to produce those consonants aspects of speech, which are and improve breath control is that I try to figure out what their com- related to control of air flow. For it reduces the rate of speech. But munication demands are and match instance, you can work on multi- it’s better to slightly reduce your that to what their abilities are and syllabic words, like “computer” or rate than to have all your conso- supplement them as needed with “Episcopal.” One strategy is called nants missing or have the stresses an augmentative system or an backward building. You take a word wrong. assistive system, whether that be like “Episcopal,” and you say “pull.” low-tech or high-tech. I’m not an You build it from the back all the Of course, the underlying neuro- augmentative technology expert, way forward. Eventually you get the muscular system is the same, but but I do know that it’s not always rhythm of what you need to say. we don’t tax it as much if we reduce an easy solution, and many times the speed. we work for years trying to find an Then you play around with the augmentative system that works stress. We work a lot on making Q: Do you have to adjust tech- best for a person’s communication the stresses come out on certain niques to disease progression? needs. words, practicing phrases such as “I SEE a ball”; “I see A ball”; and “I A: Yes, you do. Some people The bottom line is: Can they com- see a BALL.” continue to be successful with mini- municate what they want with their mal prompting. They learn how to family or in a work setting in a way Another problem in Friedreich’s adapt. But there are some people so that they’re not frustrated by it? is that consonant precision is not who require some augmentative there. [Consonants are sounds that systems [such as talking comput- Q: Can most people achieve require complete or partial closure ers] at some point. Certainly not that? of a part of the vocal tract.] A com- everybody. mon thing is not putting the final A: I think so. At least a lot of consonant on a word, so that “hat” I don’t recommend augmentative people can. However, I do think becomes “ha.” devices lightly. You can have a

21 In Focus: Friedreich’s Ataxia ©2010 MDA the communication deficit in Friedreich’s does pose a lot of to you. problems. Sometimes, people perceive Friedreich’s patients as Then, if they see that their speech not being intelligent because of the is deteriorating — for instance, if slow, labored speech. It makes it people are asking “what?” more seem like their cognitive skills are often than not, or if they’re recog- not intact. That’s far from the truth, nizing that speech is really labori- but this is a frustration. ous — they know there are things they can do to address the prob- Unfortunately, sometimes there’s lem. just less interest in interacting, because speech is a lot of work. I Some early compensatory strate- always hate to see that happen. gies could be developed that would save them effort and worry, as Another issue is that it’s hard to opposed to waiting until they’re too listen to this speech. If you’re the frustrated to talk. patient’s partner or parent, there can be an urge, when you see how much work the speech is, to fill in, to jump ahead. But it can be dev- astating to somebody that’s trying to communicate some information or a thought or an idea. It defeats somebody’s purpose in trying to communicate.

We try to work with families. As long as it takes the person to say something, we tell them to try to patiently wait it out. If the person is trying, you want to support that. It doesn’t help as much as you think to fill in for them. But it can be hard for families to be good listeners.

Q: Is it best for someone with FA to start a speech program as soon as they begin to develop problems, or does that matter?

A: We see patients at different points all the way along. I’m big on intervening early, though, so that people know what’s available. I think what helps in the very beginning is to alert people, to tell them that these are the problems that are probably going to arise, and these are the resources that are available

22 In Focus: Friedreich’s Ataxia ©2010 MDA Melinda Guttry, a physical therapist A: We try to have people work on in Rehabilitation Services at the exercise and work on stability, and University of California-Los Angeles use their muscles so that they’re Health System, has worked closely reminding the muscles of holding with neurologist Susan Perlman the body erect or sitting upright or (see page 14) and with FA patients making smoother movements. since the mid-1980s. If I have the person moving from a Q: Can you improve function in Most of her clients with FA have sitting to a standing position, I use someone who has degenerating been young adults, but she also the parallel bars and have them nerve fibers? has worked with people in their 40s practice. I start them out by help- and 50s. ing them set their muscles and use A: Yes, because there are many, their muscles in a sequence. Then, many nerve fibers, and they all Q: What kinds of problems do as they practice, they get a better don’t degenerate at one time. So you see in people with FA? feel for the sequence. They know it’s the practice of getting all the which muscles they’re using and fibers that are still functioning to do A: It’s usually movement and the feeling of the muscles as they the work, to give as much informa- coordination. The nerves aren’t coordinate them. tion to the muscles as possible. conducting information consistently, so the muscles don’t receive Parallel bars are heavier than they Q: Have you had good results? consistent signals about holding a are, and they’re long. The bars are position or making a limb have a solid and stable, and people get A: I’ve seen good results. It smooth, coordinated movement. an opportunity to isolate different depends on how much the person muscles, setting their muscles so is able to practice at home. A lot of the problem is in outgo- that their trunk is more stable. ing coordination signals from the Sometimes that’s a problem. It nervous system. But if you have On the parallel bars, if they’re trying depends on the age of the person a muscle that’s getting weaker to stand up, they might pull on the and how motivated they are to because the person is not using it, bars. I teach them to push down practice versus staying in their then the muscle doesn’t activate as instead, because if they want to chairs and doing something else. readily either. There can be prob- use a walker and they pull up on Sometimes that’s more important to lems with sensing position as well. the walker, the walker won’t stay on them than getting up and practicing the ground. walking. Q: What do you do about these problems in a rehabilitation set- I also work with them on range of But the more they’re up and the ting? motion [putting a joint through its more they practice coordinating normal movement range], to help their muscles, the more they can maintain flexibility. stay up.

23 In Focus: Friedreich’s Ataxia ©2010 MDA s a child, Gabrielle Ford studied to receive her diploma. Ato be a dancer. By the time she But afterward, she fell into was 12, she had put in countless a deep depression. She hours of rehearsing ballet, jazz and became angry at the world tap — learning the steps, standing and mean to her family. on tip-toes, doings dips, turns and spins — all the while dreaming of She spent two miserable the day when she would perform years before Izzy, a black- professionally. and-tan coonhound puppy, came into her life. That’s Then Ford’s life took an unex- when things began to (2004 photo) pected turn. She began to lose change. The final step in Ford’s redemption strength and balance. Her gait came when she and Izzy began grew unsteady. She was taken for By helping her to acknowledge visiting schools to talk to kids about a series of tests that revealed she her FA, Izzy pulled Ford out of the harmful effects of bullying. had Friedreich’s ataxia (FA). But her shell. First, Ford had to get a Ultimately, Ford was even able to knowing how much her daughter wheelchair, so Izzy would grow up speak at her old high school. She wanted to be a dancer, Ford’s comfortable around wheels. (Ford, has received dozens of letters from mother kept the news from her for however, continued to refuse the children telling her how much her six months. chair until she fell and broke her presentation meant to them, and arm.) Then Ford learned that Izzy many more inquiring about Izzy. When she learned the truth, three had liver disease, as well as a form days after her 13th birthday, Ford of muscular dystrophy that caused Even though Izzy passed away didn’t take it well. “I was in denial,” muscle weakness similar in some in May 2009, Ford, who lives in she writes in her memoir, Still ways to FA. Fenton, Mich., continues to visit Dancing. “To talk about it would schools, speaking on stage before make it real, and I didn’t want it to Izzy’s illness further forced Ford hundreds of kids about her experi- be real.” back into the world, as she had ences and encouraging them not to to take the dog to numerous doc- bully others. All through high school, Ford kept tors and hospitals, and to accept help, financial and otherwise, from her diagnosis a secret. Her condi- She did end up performing — just tion worsened, yet she refused to friends and family members. not in the way she imagined. use any adaptive equipment. As her speech slowed and she began to Ford and Izzy’s story — the two trip and fall, she endured cruel com- of them helping each other with ments and taunts, and even physi- diseases that were uncannily cal abuse from classmates. She similar — was published in local became increasingly isolated. She newspapers. Word spread about didn’t want to meet other teens with the unusual pair, and Ford got a FA, and she forbade her family from call from the cable TV channel mentioning her condition — or even Animal Planet, which wanted to film watching the MDA Telethon on TV. her and Izzy’s story for a segment about pets and their owners. The Ford’s book, as well as recent information piece aired dozens of times, and about her anti-bullying presentations, is At graduation, despite a twisted available on Ford’s website, ankle, Ford walked across the stage “Gabe ’n Izzy” became famous. www.gabeandizzy.com.

24 In Focus: Friedreich’s Ataxia ©2010 MDA rowing up, Nygel Lenz was a I had to stop driving. I could not find Gtypical active boy. He played a job.” football, soccer, basketball and baseball, and loved doing tricks like Lenz finally decided to learn all he jumping ramps with his bike and could about his disease, in order skateboard. He was diagnosed with to empower himself and others. He scoliosis at 11, but his life didn’t joined a support group, then began really change — until he had surgery leading it in 2002 and hosted a for scoliosis at age 15. His balance national meeting in 2005. worsened immediately and he began seeing a neurologist, but it took “I had a lot of responsibilities in Nygel Lenz and his fiancee, Carolyn almost four years to confirm that he terms of leading fundraisers, seeking Hunter at the 2010 Telethon in St. had Friedreich’s ataxia (FA). guest speakers, finding hotels and Petersburg, Fla. speaking,” he says. “This is only one “I experienced most of high school example of something I never would Lenz participated in a study of the wondering what was wrong with my have done if I did not have FA.” drug buspirone as a potential FA body,” says Lenz, 36, of Clearwater, treatment, but it worsened his symp- Fla. “My balance kept worsen- His confidence boosted, Lenz was toms. He also tried coenzyme Q10, ing. I stopped playing sports and able to find a job. Since 2004, he without benefit. He enjoys physical became increasingly self-conscious, has worked at the Pinellas County therapy, but his insurance does not concerned that others would see Juvenile Assessment Center, coun- pay for enough sessions per year me walk awkwardly and that girls seling troubled teenagers. Even to really make a difference. “I need would not be interested in me. I though many of the kids he counsels a PT to push me and help me exer- was scared, but I tried to maintain are criminals and gang members, cise,” he says. normalcy and only told my closest they have never given him any trou- friends.” ble — perhaps because they realize Lenz recently went back to school that Lenz knows something about to get a second master’s degree A good student, after high school struggle and hardship himself. in criminology and criminal justice, Lenz was able to complete both col- so he can get the accreditation he lege and graduate school. “I was not Like many with FA, Lenz has hyper- needs to teach college. He enjoys going to allow FA to defeat me,” he trophic cardiomyopathy. Beginning spending time with his friends and reports. “However, I must admit that in 1999, his heart would occasionally fiancee, joking, playing games, writ- I did not completely accept FA or go out of rhythm or into atrial fibrilla- ing and traveling. confront what the diagnosis meant. It tion, making him extremely short of is daunting. I used a cane for a cou- breath, sweaty and exhausted. The Active in fundraising and other activi- ple of years, a walker for a couple symptoms have gotten much better ties for MDA, Lenz received the MDA of years, and I finally began relying since Lenz underwent two radio- Robert Ross Personal Achievement upon a wheelchair after graduate frequency ablations (a procedure that Award for the state of Florida in school (in 2001). uses high-frequency radio waves to 2009. At 36, he has lived more than treat the heart’s electrical conduction half his life with Friedreich’s ataxia. “I experienced stares and questions. system) in 2004 and 2006. He cur- I still do. I experienced rejection from rently gets echocardiograms about “Of course I would prefer to not have girls. I avoided going to events that I once a year, and monthly EKGs and had FA, but it has helped me gain wanted to attend, like Gator football monitoring of the heart medications some perspective and determine games when I was a student there. he takes. what is important in life — and who the important people in life are.”

25 In Focus: Friedreich’s Ataxia ©2010 MDA iagnosed as bipolar and autistic Dwhile still a child, Bridget Morris grew up with a host of develop- mental problems. That’s why, when she was tested for Friedreich’s ataxia (FA) at age 10, her mother, a nurse, was “very cavalier.”

Bridget had muscle tightness, weakness and scoliosis (a curved spine), her handwriting was worsening, and she had begun to fall and walk with a “wide” gait to steady herself. Nevertheless, her mother was shocked when told her daughter had FA. “When I think of that moment on the phone, hearing those impossible words, I still feel an icy chill in my bones, and the hairs on the back of my neck stand up,” Alicia Morris says.

Growing up, Bridget could be engaging and witty, and was good at languages, especially Russian and French. She learned to read and write in Cyrillic and can read Chekov in Russian. Yet she also could be aggressive and combat- ive, and needed physical, speech and occupational therapy. She had dren with special needs and gets progress. been on a multitude of prescrip- around in a manual wheelchair. Her tion mental health drugs since speech has slowed a bit, but she She says she has a lot of hope kindergarten, which is one reason so far has escaped heart problems, about the progress of research in her mother initially discounted the diabetes, and vision or hearing FA, and encourages other FA fami- idea that Bridget also had muscle problems, which are frequent symp- lies to get involved in fundraising disease. toms of FA. and to participate in studies, where appropriate. “We used to think FA was the least Her mother advises other parents of our problems,” Alicia Morris of children with FA to get support “Working hard toward a cure gives says. “Not anymore.” from an FA parent group, and to purpose and a goal to something take family trips as soon as pos- over which we have no real con- Now 20, Bridget, of Littleton, Mass., sible, because traveling can be trol,” notes Bridget's mom, Alicia. attends a residential school for chil- more difficult once FA symptoms

26 In Focus: Friedreich’s Ataxia ©2010 MDA inalben “Pinky” Patel was born a pacemaker implanted to regulate Pin a village in Western India and my heartbeat and surgery was moved to the United States with her scheduled.” She now has a pace- family four years later. She already maker, which she gets checked was starting to show symptoms of twice a year. Friedreich’s ataxia (FA). By the time Patel started college, “My aunt and cousin took me trick- she needed help with all her per- or-treating for the first time,” she sonal care. “People asked why I says. “When we got home, my aunt drove my wheelchair so drunken- complained that I kept falling down like, why I didn’t transfer myself to on purpose for attention. A couple and from my wheelchair, or why I years later my kindergarten teacher couldn’t dress and bathe myself like noticed that I wasn’t placing my feet that other wheelchair-user. where there are two noises or more the way I should when walking.” occurring at once.” “Of course those comparing queries Patel received an FA diagnosis aggravated me, but I kept the anger Patel also was unaware that her when she was 11 years old, and in my mind. Instead of raging at weakened eyesight was the result began using a power wheelchair the askers, I calmly educated them of FA until she met others online at age 13. At first, she was able about FA. They are not asking to who also were in her situation. to transfer in and out of the chair be rude; they are just ignorant. Even after LASIK (corrective) sur- by herself, or with minimal assis- There are so many different disabil- gery, Patel has shaky vision, poor tance. Throughout high school she ities out there, and everyone can’t depth perception and wears pre- maintained the ability to bathe, know about every disability.” scription glasses. brush her teeth and get dressed by herself. During Patel’s last year of high Patel received a journalism degree school, she developed a hearing from Murray State University in “The beginning of my progression problem. “My friends would tease Murray, Ky., and now works as a from just wheelchair user to ‘FA-er’ me,” she says. “They said that I freelance writer in Paducah. was in the sophomore year of high only listen to what I want to hear. I school, when I was diagnosed with remember getting annoyed at their “I have been lucky to have friends insulin-dependent diabetes,” reports taunting. I never liked being made from school (who stopped teas- Patel. fun of about anything related to my ing me after I explained about the disability, but I did not know that AN) and my support groups,” Patel this problem was also related to While Patel was in the hospital, the says. “I don’t care what strangers FA.” doctors also found a thickening of or distant relatives think of me. her heart walls, and she began taking medication for that, too. It wasn’t until Patel graduated from “The most important knowledge college and began attending sup- is that the people who are close Two years later, Patel fainted at port groups that she learned her to you understand your condition. school and went to the emergency hearing problems were caused by Don’t worry about others. It is the room. “When I got to the hospital, FA. “It’s called auditory neuropa- only way to live!” the doctors found that I had bra- thy (AN), and it basically means dycardia, a fancy name for slow I cannot hear well in crowds, on Pinky Patel has a website at heartbeat. They decided I needed the phone, and any other situation http://pinkdreams_1.tripod.com.

27 In Focus: Friedreich’s Ataxia ©2010 MDA hen Kayla Prather was 8 when I am, she attends Wyears old, she began having my classes, takes trouble with her balance. Her mom notes and collects my took her to a pediatrician, who homework for me. That tested her reflexes and found she way I don’t fall behind.” didn’t have any. Prather visits the MDA More tests followed, including one clinic and a cardiolo- of Kayla’s DNA, and the diagnosis gist for checkups every of Friedreich’s ataxia (FA) was con- six months. She is on firmed. the drug metoprolol to treat hypertrophic car- Prather, of Hiram, Ga., says the diomyopathy, a thicken- disease didn’t bother her much at ing of the heart muscle first. She still could run around and that is a common prob- play with her friends in the neigh- lem in FA (see Treating borhood. But as her symptoms the FA-Affected Heart worsened and her ability to get on page 18). She also around decreased, she became takes asthma medica- less social. Now, she says, she has tions and has been few friends outside of school. treated for scoliosis and stomach pains. support groups and awareness “It’s difficult to go to my friends’ campaigns and to not give up. houses or spend the night because Her vision is good, but she has their homes are not accessible,” slight hearing loss and her speech “Remember, we can do most any- Prather says. “Even just to go off is beginning to soften and slur. “I thing that others do, but we just with my friends is difficult. Usually I usually end up repeating myself have to learn to do it differently. will meet my friends at the movies a lot, and sometimes I have to try Keep on persevering — don’t give and then maybe go to dinner, but to speak louder but it tires me out up!” my mom has to take me and then when I do that.” pick me up, and take me to the dinner location because I can’t ride Prather enjoys reading, surfing the with my friends.” Internet and going to movies. She loves the “Twilight” movies, once At school, Prather uses a power even attending a midnight showing. wheelchair full time and has a She also is active in FA support MDA’s website is constantly updated “parapro,” or assistant, assigned groups and awareness campaigns, with the latest information about the diseases in its program. to her. “My parapro and I are very and has gone door-to-door to raise close,” she says. “She goes with money for MDA. mda.org • (800) 572-1717 me to all my classes and lunch. When I am tired, she takes notes She encourages other young ©2010, Muscular Dystrophy for me. I’m out of school a lot and people with FA to get involved with Association Inc.

28 In Focus: Friedreich’s Ataxia