Friedreich’s Ataxia: An overview of current trials being offered through USF

19th Nov 2015 Friedreich's Ataxia

Friedreich’s ataxia was first recognized by Nikolaus Friedreich over 150 years ago.  For nearly two decades, researchers have been focused on identifying the underlying cause of FA and treatments to reduce symptoms and cure this disease.

There are a number of investigational drugs and treatments which are currently in clinical trials. Here locally in Tampa, The University of South Florida (USF) Ataxia Research Center is leading the way in testing and developing new treatments.  USF is one of 10 sites in the international Friedriech’s Ataxia Research Alliance (FARA) collaborative clinical research alliance.  Some novel approaches are being used to increase frataxin production, reduce mitochondrial damage while improving overall mitochondrial function, reducing oxidative stress, and delivering gene therapies.

Here is an overview of the current FA related clinical trials being conducted through the USF Ataxia Research Center:

Randomized, Double-blind Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients with FA.  RT001 is a compound developed by a Retrotope (clinical-stage pharmaceutical company).  The patented drug is a stabilized fatty-acid that is aimed at shutting down degradation of cellular membranes that are believed to be associated with neurodegenerative diseases and the aging process.

Phase I, Randomized, Double Blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral VP 20629 in Adult Subjects with FA.   This study sponsored by biopharmaceutical company, Shire, is focusing on a low molecular weight drug (indole-3-propionic acid). This is considered a powerful antioxidant to help alleviate free radical damage from iron buildup from within the cells.

Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich’s Ataxia (MOXl1).  RTA 408 compound, developed by Reata Pharmaceuticals is believed to activate the Nuclear Factor 2 pathways which regulates the expression of antioxidant proteins. This study will be conducted in two parts. The first is to test the study drug at various dose levels. The second part of the trial will be focus on two specific dose levels of RTA 408 as compared to a placebo.


Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Pharmacokinetic Study of ACTIMMUNE in Children and Young Adults with FA.  Interferon gamma-1b is a biologically manufactured protein that is similar to the one produce by the body’s own immune system. This drug is already approved in the U.S.  for two rare diseases and has received fast track approval by the FDA in the treatment of FA. Interferon gamma plays a role in the regulation of iron availability.  From previous trials, this drug has shown the potential to increase the production of frataxin protein.

Cardiomyopathy in Friedreich’s Ataxia

18th Sep 2015 Diseases, Friedreich's Ataxia

A recently published study conducted through the New York Veterans Affairs Medical Center in Albany, looked at the association between Friedreich’s Ataxia (FA) and cardiomyopathy. While FA is known as a neurological disease, the most common cause of death in FA patients is cardiomyopathy. By definition, cardiomyopathy is a disease in which the myocardium becomes weakened or stretched resulting in decreased ability to pump blood to the rest of the body. As this progresses, arrhythmias and heart failure may result.

The study focused on 28 autopsy heart tissue samples from patients with FA. Additionally, 10 tissue samples were taken from healthy controls. Multiple measurements were made including X-ray fluorescence (XRF) of iron and zinc within the ventricle walls and interventricular septum, tissue frataxin, iron histochemistry, inductively-coupled plasma optical emission spectrometry (ICP-OES), and immunofluorescence of inflammatory markers hepcidin and CD68. Prior studies have focused on abnormalities related to left ventricular hypertrophy, dysfunction, and electrical abnormalities.

The tissue samples from hearts from FA patients showed evidence of hypertrophy and thickened walls. Muscle cells, known as cardiomyocytes were identified to be considerably larger in the control hearts. Additionally, the cardiomyocytes were surrounded by a layer of endomysium (fibrous connective tissue).

Further analysis of the tissue samples revealed a significant reduction in cardiac frataxin levels and higher levels of iron within the left ventricular wall and septum in FA patients. Furthermore, an abnormal number of CD68 reactive inflammatory cells was found in the hearts of FA patients. Cytosolic ferritin sequesters and stores iron to protect against free radical damage while hepcidin is a protein that plays a major role in iron regulation. Both of these markers were elevated in FA. The results of this study point have lead the researchers to believe that a strong iron expression seen in the cardiomyocytes might be a unique finding for cardiomyopathy in FA hearts. Since frataxin levels were low, the restoration of this mitochondrial protein and targeted anti-inflammatory therapy may be beneficial for those with FA.

The study was funded by the Friedrich’s Ataxia Research Alliance (FARA), National Ataxia Foundation, and the National Institutes of Health


Koeppen AH, Ramirez RL, Becker AB, Bjork ST et al. The Pathogenesis of Cardiomyopathy in Friedreich Ataxia. PloS One. 2015 Mar 4;10(3).

Alboliras ET, Shub C, Gomez MR, Edwards WD. Spectrum of Cardiac Involvement in Friedreich’s Ataxia: Clinical electrocardiographic and echocardiographic observations. American Journal of Cardiology. 1986 Sept 58(6): 518-524.

Scoliosis Associated with Friedreich’s Ataxia

The incidence of Friedreich’s Ataxia (FA) is approximately one in every 50,000. It is known that most symptoms associated with FA occur during the first decades of life. Many lose their ability to walk by age 25. Friedreich himself noted the presence of scoliosis along with other symptoms in 1875. Scoliosis is associated with FA and is often seen early on in the developmental process. A search of the literature finds that the prevalence of scoliosis among those with FA has been reported in the range of 63 to 100%1, 2, 3

There is some debate noted on whether FA should be classified as a neuromuscular scoliosis or idiopathic type. For the most part, scoliosis associated with FA is similar to other neuromuscular forms such as muscular dystrophy which features a progressive thoracolumbar curve and severe muscle weakness. Labelle et al (1986) concluded that scoliosis associated with FA behaved more like an idiopathic form as the curves were not necessarily rapidly progressive, were similar curve patterns, were not associated with muscle weakness, and age at onset was a key indicator of progression4. This was based on a retrospective review of 56 cases with an average of nine years of follow-up after the diagnosis was made. This is contrary to the findings of Milbrandt et al (2008) who felt the curve patterns were more in-line with neuromuscular type scoliosis.

The current literature does reflect bracing does not appear to halt progression of most curves that have been studied. A posterior spinal fusion has become the main treatment choice for surgical management of progressive curves associated with FA. Previously, hook and wire constructs were utilized but has fallen out of favor due to inability to maintain correction. Many of the curves are double major type with kyphotic deformity. Restricted lung disease associated has been reported as a secondary complication in cases with significant kyposcoliotic deformity. Cardiac co-morbidities are also associated with FA and must be considered when contemplating surgical management.

Despite known complications associated with FA, reported outcomes from posterior fusion surgery have demonstrated successful correction of the major deformity and fusion rates at an average of 3 years of follow-up.

1 Milbrandt TA, Kunes JR, Karol LA. Friedreich’s ataxia and scoliosis: the experience at two institutions. Journal of Pediatric Orthopedics. 2008 Mar; 28(2) 234-238.

2 Daher YH, Lonstein JE, Winter RB, Bradford DS. Spinal Deformities in patients with Friedreich ataxia: a review of 19 patients. Journal of Pediatric Orthopedics. 1985 Sep-Oct; 5(5): 553-557.

3 Cady RB, Bobechko WP. Incidence, natural history, and treatment of scoliosis in Friedreich’s ataxia. Journal of Pediatric Orthopedics. 1984 Nov; 4(6) 673-676.

4 Labelle H, Thome S, Duhaim M, Allard P. Natural history of scoliosis in Friedreich’s ataxia. JBJS. 1986 Apr; 68(4): 568-572.

MOXle Study: Evaluating the drug RTA 408 in the treatment of Friedreich’s Ataxia.

A clinical trial for a novel medication to treat Friedreich’s Ataxia was announced this past week. Reata Pharmaceuticals, a privately held biopharmaceutical company based out of Texas, announced the beginning of enrollments for a phase 2 and 3 clinical study titled “MOXle – RTA 408 Capsules in Patients with Friedreich’s Ataxia.” The study aims to further evaluate the safety, efficacy and pharmacodynamics of the treatment medication. A randomized, double blind, study to evaluate the maximum tolerated dose will be part one of the study. Part two will consist of splinting participants into two groups and giving two different dose levels of RTA 408. The second part will also be a randomized, placebo-controlled, double blinded study. This will be a multi-center study in which 52 patients are being sought.

Two clinical interests of the study will be peak workload during exercise as well as the modified Friedreich’s ataxia rating scale (FARS). The latter is a measurement tool which monitors proficiency of patients during activities. Additional biochemical endpoints will also be evaluated. Treatment with the study medication or placebo will be given to patient’s once daily for twelve weeks.

Nrf2 or Nuclear Factor 2, is a protein that regulates the expression of antioxidant proteins that protect against oxidative damage. Friedreich’s Ataxia is caused by defects in the gene for frataxin which is involved in the regulation of iron levels in the mitochondria. In pre-clinical studies, lower expressions of Nrf2 were correlated with frataxin deficiency and lower mitochondrial function. It is believed that RTA 408 can activate the Nrf2 pathways and improve mitochondrial function. Taken from animal models, RTA 408 showed the ability to improve overall cellular metabolism.

The study is expected to achieve final outcome measures by the spring of 2015 and study completion closer to June 2016.

Dr. Susan Perlman and Stephanie Magness on American Health Journal Nov 7

Dr. Susan Perlman appeared on American Health Journal this Friday to discuss Friedreich’s Ataxia (FA) along with one of her patients, Stephanie Magness. They educated viewers on the clinical aspects of the disease as well as daily life and clinical studies.

Dr. Perlman is a professor in the Department of Neurology at the David Geffen School of Medicine at UCLA and physician specializing in ataxia, Huntington’s Disease, and neurogenetics. She is the Director of the Ataxia and Neurogenetics Program and the Post-Polio Program at UCLA and has been a primary investigator for many Friedreich’s Ataxia trials over the years.

In this program, Dr. Perlman reviews some of the basic facts of the disease – it is a recessive neurogenetic disorder caused by mutations in both copies of the gene that controls the production of frataxin, it is a disease of childhood, and the symptoms start with balance and coordination difficulties. It begins in the legs and progresses to the hands, speech, vision, and even hearing. The patients may also develop cardiac symptoms, which include hypertrophic cardiomyopathy, heart rhythm problems, and even heart failure. Diabetes is another potential symptom and can cause affected individuals to require insulin.

Stephanie Magness is currently one of Dr. Perlman’s patients and, like all too many people with FA, she was not diagnosed correctly for the first few years of her symptoms. Friedreich’s Ataxia is often misdiagnosed as another recessive childhood neurogenetic disease like Charcot-Marie-Tooth disease, cerebral palsy, and idiopathic peripheral neuropathy. She was eventually diagnosed correctly via gene testing and is now able to manage her symptoms accordingly. Stephanie has also taken part in a natural history study as well as a clinical drug trial – possibly the first approved drug for FA.

According to Stephanie one of the most difficult aspects of the disease is its progressive nature. Even if a patient is able to handle their symptoms well currently they know that it may all change. Her advice was to focus on what you can do instead of things that you obviously cannot and find new things to do that you can excel in.

Now that drug companies have begun to take an interest in Friedreich’s Ataxia and to see it as an important area scientifically there is hope that a drug will be approved to treat FA in the not-too-distant future. Watch the program on Vimeo here: (the section about Friedreich’s Ataxia starts at 15:39)


Puccio Study FA

19th Sep 2014 Diseases, Friedreich's Ataxia

A recent breakthrough in Friedreich’s ataxia (FA) research gives hope that gene therapy can prove be an effective treatment for the disease. A team led by Hélène Puccio, Ph.D., has demonstrated that gene therapy can be used to reverse heart damage caused by FA and correct mitochondrial metabolism. Dr. Puccio works as the head of a research team at the Institute of Genetics and Molecular and Cellular Biology located at the University of Strasbourg, France, as well as research director at the Insititute de Santé et de la Recherche Médicale (INSERM.) She and her team have concentrated their research on the pathophysiological mechanisms involved in recessive ataxias, like FA, in order to develop new animal and cell models.

Friedreich’s ataxia is rare, but one of the more common recessive ataxias – found in 1 in every 50,000 births. It is caused by a mutation in the frataxin (FXN) gene, which in turn causes a decrease in the amount of frataxin produced. The lack of frataxin disrupts the mitochondria that are responsible for the cell’s energy production, and, unfortunately, heart tissue is particularly vulnerable.

While FA causes progressive neurodegeneration that starts as impaired balance and coordination, it also impairs heart function and can contribute to diabetes. Most patients require a wheelchair after about 10-20 years of disease progression, but complications with the heart lead to death in more than half of individuals, and often before the age of 35.

Dr. Puccio’s team used a harmless viral vector to insert a normal copy of the problematic gene in the heart cells of FA mouse models. Since these mice show the same heart symptoms as human patients suffering from the disease the results are especially promising. The virus used was an adeno-associated virus (AAV) since it is known to effectively and efficiently target heart cells and express therapeutic diseases. This virus was modified to render it harmless and only capable of inserting the normal FXN gene copy into the cells.

One single intravenous injection was not only able to prevent the development of heart disease in the mice, but it quickly and completely reversed the heart damage in advanced cases. Within three weeks the mice appeared to have completely restored heart and mitochondrial function and their heart tissue appeared similar to healthy mice.

Since this is the first time that gene therapy has produced such a fast and complete remission of heart disease in an animal model work is rapidly being done to begin clinical studies. There is also hope that this technique can be used to prevent or even correct damage to the spinal cord and cerebellum.

FARA Energy Ball Research Panel

19th Sep 2014 Diseases, Friedreich's Ataxia

There were many excellent speakers at this year’s FARA Energy Ball that covered a wide variety of topics – from recent scientific breakthroughs to first-hand experiences of those suffering from the disease. Three leaders in the Friedreich’s ataxia research community spoke regarding current genetic approaches to therapies and shared some of their most recent findings.

One of the speakers was Joel Gottesfeld, Ph.D. Dr. Gottesfeld currently works as a professor in the Department of Molecular Biology at the Scripps Research Institute. He studies several genetic human diseases – one of which is Friedreich’s ataxia. In addition to studying general characteristics of this disease Dr. Gottesfeld and his staff are working to develop new treatments.

Their research has led to the discovery of a new group of histone deacetylase (HDAC) inhibitors. These small molecules were found to reverse the heterochromatin-mediated silencing of the frataxin (FXN) gene. Further research with mouse models has shown that these HDAC inhibitors can cross the blood brain barrier, do not appear to cause toxicity at expected therapeutic levels, and do act as HDAC inhibitors in the mouse brain. Even more promising, they demonstrated that the HDAC inhibitors increased the FXN gene expression and protein in the blood cells of FA patients.

Another speaker was Hélène Puccio, Ph.D. Dr. Puccio is the head of a research team at the Institute of Genetics and Molecular and Cellular Biology located at the University of Strasbourg, France, as well as a research director at the Insititute de Santé et de la Recherche Médicale (INSERM.) She has concentrated her research on the pathophysiological mechanisms involved in recessive ataxias, like Friedreich’s ataxia, in order to develop new animal and cell models.

During one of her studies she and her colleagues were able to use mice with no frataxin in their heart to demonstrate that gene therapy can be used to reverse heart damage and correct the mitochondrial metabolism. This finding leads to the possibility of using gene therapy as a treatment for the disease.

Finally, Massimo Pandolfo, MD works for Université Libre de Bruxelles at the Hôspital Erasme and has been the principal investigator of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS.) Dr. Pandolfo led an international collaboration that discovered the FA gene back in 1996 and has continued to contribute in many ways over the years. He has been working with everything from research trials to clinical care for patients. In addition, he has contributed to our understanding of the disease process, clinical characteristics, and has helped to advance drug development.

FA Dyclonine Study Review

19th Sep 2014 Diseases, Friedreich's Ataxia

Freidreich’s ataxia (FA) is a recessive disease causing progressive damage to the nervous system. It is the most prevalent inherited cause of ataxia and affects about 1 in 50,000 people in the United States. Despite its prevalence, there is no cure or treatment beyond supportive care.

A recent article was published in the Human Molecular Genetics journal in regards to a potential new therapy for FA. The drug, dyclonine, was developed for use as a topical anesthetic and is found in the over the counter throat lozenge, Sucrets, as well as some Cepacol throat sprays. FA is caused by a genetic deficiency in the mitochondrial protein frataxin (FXN) and dyclonine was noticed to increase FXN protein in animal models. When the drug was given a mouse model of FA it prevented a performance decline during balance beam tests. A proof-of-concept clinical study was performed on eight patients, which showed an increase in buccal cell FXN.

Mice used in this study were tested with level balance beams of varying thickness that required them to walk from one end to the other in order to seek shelter. Mice were timed and video recorded in order to count the number of foot slips. The individual in charge of recording the data was blinded to which treatment group the mouse was in. Mice that were dosed with dyclonine had statistically significant improvements. Not only did their performance on the beams not worsen like the affected controls, but they even improved their time to cross.

The second part of the study involved using dyclonine as an oral rinse, since that is already FDA-approved, and then swabbing the cheeks for buccal cells. The cells were compared to pre-treatment cells from the same patients. Six of the eight showed an increase in FXN, two showed no increase, but two healthy controls showed increased levels. Interestingly, the patients with the most neurological impairment were the ones that showed the highest increase from the dyclonine mouth rinse. Neurological impairment was determined with a FARS (Friedreich’s Ataxia Rating Scale) score.

What’s next? Further clinical studies are required to see if the results achieved from the oral rinse can be duplicated systemically and show the same improvements as observed in the mouse model. Additionally, optimal dosing, toxicology, and pharmacokinetics all need to be studied and better understood before testing can proceed. Despite the questions that still need addressed, dyclonine could be a new treatment option for people affected by Friedreich’s ataxia.

Patients with Friedreich’s Ataxia Are Fighting Back

25th Jul 2014 Friedreich's Ataxia

Friedreich’s Ataxia impacts one in every 50,000 people within the United States. This neurological disorder can impact people of all ages but typically starts in childhood. The disease ravages the body to the point that most people only live ten to twenty years after being diagnosed before they need help of a wheelchair and eventually become incapacitated. This is a terrible way to live, and Dr. Robert Dean has been working with the Friedreich’s Ataxia Research Alliance (FARA) to help find a cure.

Recently, several people diagnosed with the disease have decided to fight back. Rather than being held down by the disease, they are stretching the boundaries of what it means to be someone diagnosed with it. In so doing, they are raising needed awareness and funds for the cause.
Barry Rice, a 34-year-old man from Ireland, has participated in putting together the first race for Friedreich’s Ataxia in the area. Cycle Ataxia will take place on August 10th in Ashbourne, and Mr. Rice is hoping that 500 cyclists will participate. He will be on hand in his wheelchair, participating in the event as much as possible. He was diagnosed with late onset Friedreich’s Ataxia and is able to do more things that many people who suffer from the disease. Still, he is confined to a wheelchair and has difficulty doing simple tasks like tying his shoes. He wants to raise awareness so that others suffering from the disease know they are not alone, and more money can go towards research.

The Fryatt family will be climbing Mt. Kilimanjaro this October to raise awareness for the disease. This would be a feat in and of itself but is made more so by the fact that Iain Fryatt has Friedreich’s Ataxia. Climbing a mountain would seem out of reach for most people suffering from a neurological disorder but the Fryatt family is determined. He will be using a Mountain Trike to ascend the mountain. The device will allow him to steer using a lever, and it will be the very first time someone has attempted to climb Kilimanjaro using one. The climb will take them over a week, and they are hoping to raise over $10,000 for the climb. The money will then be given to research.

Both Barry and Iain are not letting Friedreich’s Ataxia slow them down or define their life. They are true heroes that are committed to using their abilities to help others suffering from the disease. Instead of focusing on what they cannot do, they are focusing on what they can do.
As a humanitarian and physician, Dr. Robert Dean believes in the power of joining together to support a cause. Since working with FARA, he has witnessed money going into research with clear results. They now know what causes Friedreich’s Ataxia and are testing ways to implement a cure. There is still a long ways to go but with scientists, community leaders, patients and physicians like Dr. Dean working together, anything is possible.

Dr. Robert Dean and the Friedreich’s Ataxia Research Alliance (FARA)

08th Jul 2014 Diseases, Friedreich's Ataxia

Dr. Robert Dean is actively involved with the Friedreich’s Ataxia Research Alliance (FARA) and working with them on ways to help find a cure. Friedreich’s Ataxia (FA) is a condition that causes damage to the nervous system. It will often start in childhood and worsen over time until it begins to impair movement. The disease impacts around 1 in every 50,000 people within the U.S. Unfortunately, the disease did not get very much attention, funding, or research until FARA was founded. The organization has led the awareness and research efforts since 1998 and continues to do so today.

What are the symptoms of Friedreich’s Ataxia?

The disease impacts people in different ways but generally speaking the symptoms will start to occur between the ages of five and fifteen. It typically starts by making it difficult for people to walk with the Ataxia spreading into the arms and core. Some patients will also lose their tendon reflexes and suffer from scoliosis. As time goes on patients may start to have their speech slur and develop hearing and vision loss, as well.

In addition to making large impacts on their ability to move, patients find it difficult to recover from common illnesses like colds and the flu. They become fatigues more easily and frequently suffer from chest pain, shortness of breath, and heart palpitations, common symptoms that result for accompanying heart disease.

Once the symptoms have started manifesting most patients only have ten to twenty years before they are confined to a wheelchair and eventually become incapacitated. This is incredibly devastating considering that most people start to suffer from Friedreich’s Ataxia when they are small children. By the time they are teenagers they could be permanently confined to a wheelchair.

How FARA Helps Patients

FARA was established in 1998 by a dedicated group of scientist and patient families that were determined to learn everything they could about the disease, what causes it and how to cure it. Their efforts have been successful in that millions of dollars have been poured into FA research and clinical trials throughout the world. With drugs in clinical trials, FARA continues to work on funding and creating public, private partnerships to further research and development.

Dr. Robert Dean and FARA

When Dr. Robert Dean became aware of Friedreich’s Ataxia, he was moved beyond measure. Witnessing small children suffer from an incurable genetic disease was something he could not stand by and watch. Listening to patients tell stories of heartbreak and learning to overcome their condition was inspirational and motivating. When children and young adults can be so confident in the face of a debilitating disease it brings what needs to be done into focus and Dr. Dean had to get involved. He has since been focused on bringing awareness to the disease, FARA, and the patients that are impacted by it. Through participation in various programs and fundraising activities, Dr. Robert Dean continues to push forward and partner with FARA to find a cure for those that need it most.

He invites you to join him in these efforts by learning more about FARA, volunteering, or donating so that those suffering from the disease can lead longer and fuller lives. To contact Dr. Dean, email