MDA leads the search for treatments and therapies for Friedreich's ataxia (FA). The Association also provides comprehensive supports and expert clinical care for those living with FA.
In this section, you’ll find up-to-date information about Friedreich's ataxia, as well as many helpful resources. This information has been compiled with input from researchers, physicians and people affected by the disease.
As you learn more about FA, always remember that you’re not alone. MDA is here for you and your family, standing ready to provide help and hope. There is a place for you in the MDA FA community.
MDA provides support by:
Once you sign up with your local MDA office , you’ll begin receiving MDA’s quarterly Quest  magazine, where you’ll find news about research and health care, helpful products and devices, social and family issues, and more.
In addition, MDA will keep you informed through e-alerts, educational publications and speakers, seminars, videos and newsletters.
Please know that there’s a role for you in the fight against Friedreich's ataxia. The MDA community is strong and dedicated, with opportunities for involvement at all levels, such as:
Please know that there’s an important role for every member of the FA community. We urge you to contact your local MDA office  to learn more.
An FA diagnosis doesn’t mean an end to your hopes and dreams. Changes, challenges and adaptations lay ahead, but also opportunity, fulfillment, joy and hope for a future free of Friedreich's ataxia.
Never forget that MDA is here to help.
|FA affects the heart and parts of the nervous system involved in muscle control and coordination.|
First described by German physician Nikolaus Friedreich in 1863, Friedreich’s ataxia (FA) is a neuromuscular disease that mainly affects the nervous system and the heart.
FA affects about one in 50,000 people worldwide, making it the most common in a group of related disorders called hereditary ataxias. It shouldn’t be confused with a group of diseases known as autosomal dominant spinocerebellar ataxias.
FA's major neurological symptoms include muscle weakness and ataxia, a loss of balance and coordination. FA mostly affects the spinal cord and the peripheral nerves that connect the spinal cord to the body’s muscles and sensory organs.
FA also affects the function of the cerebellum, a structure at the back of the brain that helps plan and coordinate movements. (It doesn’t affect the parts of the brain involved in mental functions, however.)
FA's effects on the heart range from mild abnormalities to life-threatening problems in the heart’s musculature. For more, see Signs and Symptoms .
FA is a hereditary disease, caused by a defective gene that can be passed down through a family. Mutations in the gene that carries instructions for a protein called frataxin result in diminished energy production in cells, including those of the nervous system and heart. For more, see Causes/Inheritance .
Onset is typically between 10 and 15 years of age, but FA has been diagnosed in people from ages 2 to 50. FA progresses slowly, and the sequence and severity of its progression is highly variable. Although there's no cure for FA as yet, treatments exist for cardiac symptoms, and there are ways to manage ataxia and muscle weakness. Many people with FA lead active lives, going to college, holding careers, getting married and starting families.
Scientists are making definite progress toward better treatments for FA. In clinical trials, certain drugs have shown promise for slowing and even reversing the cardiac abnormalities in the disease. For a complete discussion of current research in FA, see Research .
See In Focus: Friedreich's Ataxia  for a 2011 report on the status of FA research and treatments.
In Friedreich's ataxia (FA), the sequence and severity of symptoms varies greatly from person to person. Ataxia, or loss of balance and coordination, is usually the first symptom noticed. Other symptoms — including cardiac problems — may appear later.
See Medical Management  for information about dealing with these symptoms.
The topics covered in this section include:
|FA doesn’t impair the intellect.|
Usually, ataxia first affects the legs and torso, causing frequent tripping, poor performance in sports or just an unsteady walk. Balance and coordination continue to decline over time, and muscles in the legs become weak and easily fatigued, making it increasingly difficult to walk.
Several years later, people with FA may have difficulty with speech, and their words might come out in a slow, jerky pattern. This problem, known as dysarthria, is caused by incoordination and weakness of the tongue and other facial muscles, not by an impairment of language skills or intellect.
Someone with the "typical" form of FA might begin using a wheelchair anytime between five and 15 years after disease onset.
Some people with FA also develop swallowing difficulties, which can allow food to enter the airway, and cause choking or respiratory infections.
Many people with FA who’ve lost the ability to walk maintain their upper-body strength and coordination for several years afterward. Later in the disease, ataxia and weakness of the arms and hands may interfere with the performing of fine manual tasks like writing or manipulating buttons and zippers.
Spasticity (muscle tightness) is not an uncommon complaint of people with FA, and may be especially prominent in late-onset cases.
Back to top 
Curvature of the spine (above) affects about two-thirds of those with FA.
People with FA often have pes cavus (below) or other skeletal abnormalities
Loss of tactile (touch) sensation is a cardinal symptom of FA but is often detectable only through laboratory testing.
Vibration sense and position sense (awareness of where the body is positioned in space) are impaired early in the disease, and perception of light touch, pain and temperature may be affected later.
Most people with FA also have reduced or absent leg reflexes, such as the knee-jerk reflex.
In a small fraction of people, FA leads to hearing loss or visual impairment.
Certain skeletal abnormalities are common in FA.
Many people experience inversion (inward turning) of the feet, and a little over half have pes cavus — a shortened foot with a high arch. For people who are still walking, these conditions can cause painful blisters and calluses.
About two-thirds of people with FA develop curvature of the spine, or scoliosis, which can be painful and interfere with breathing by changing the shape of the chest cavity.
These skeletal abnormalities probably occur because some muscles have weakened while others have remained strong, pulling the bones into abnormal positions.
Back to top 
Heart failure is a leading cause of death in FA. Cardiac abnormalities occur in about 75 percent of people with FA, but they vary widely in severity.
|FA may lead to enlargement of the myocardium, the muscle layer of the heart.|
Some people with FA have abnormalities so mild that they’re noticeable only through specialized laboratory testing, while others may have life-threatening cardiac problems.
The cardiac abnormality most often seen in FA is hypertrophic cardiomyopathy, an enlargement of cardiac muscle that shrinks the blood-filled chambers in the heart, decreasing its pumping capacity and leading to heart failure.
Enlargement of the heart also can lead to arrhythmia — a heartbeat that’s too fast or too slow, and doesn’t adjust efficiently to the body’s demands. Arrhythmias can be life-threatening.
Extreme fatigue, chest pain, shortness of breath, lightheadedness, palpitations and/or pooling of blood in the ankles could be symptoms of declining cardiac function.
It’s a good idea for people with FA to have regular checkups with a cardiologist.
For more, see Treating the FA-Affected Heart .
Back to top 
About 10 percent of people with FA have diabetes, and another 20 percent have a form of "pre-diabetes" called glucose intolerance. Both occur when the pancreas decreases its production of insulin, which helps the body store and utilize sugar (glucose).
In FA, these conditions appear to be a direct result of frataxin deficiency in the pancreas.
Back to top 
|MDA clinic physicians begin with a physical exam to determine a neuromuscular disease diagnosis.|
Friedreich's ataxia (FA) typically has its onset in childhood, between 10 and 15 years of age, but has been diagnosed in people from ages 2 to 50. A later onset is usually associated with a less severe course.
A neurologist will use several tests to reach a diagnosis of FA. Typically, diagnosis begins with a basic physical exam and a careful assessment of personal and family history.
During the physical exam, the neurologist is likely to devote special time and attention to testing reflexes, including the knee-jerk reflex. Loss of reflexes occurs in most people with FA.
Perhaps most importantly, cells in the blood provide DNA (genetic material) that can be used for genetic testing. Tests for frataxin mutations  are highly reliable and can be used to confirm or exclude a diagnosis of FA in almost all cases. The tests also can be used prenatally and to determine carrier status (see Causes/Inheritance ). For more on getting a definitive genetic diagnosis, see The Genie's Out of the Bottle: Genetic testing in the 21st century .
At some point, specialized tests  may be ordered to evaluate the function of muscles and nerves. Electromyography (EMG) is done by inserting a needlelike electrode into a muscle and recording the electrical signals it generates during contraction.
A nerve conduction velocity test (NCV) is done by placing surface electrodes on the skin at various points over a nerve. One electrode delivers small shocks to the nerve and the others record the nerve’s responses. Those responses are typically smaller than normal in people with FA, because FA damages the nerves.
Computerized tomography (CT scan) or magnetic resonance imaging (MRI) might be performed to look for extensive changes in the cerebellum, which are more common in spinocerebellar ataxias than in FA.
Samples of blood and urine are checked for chemical imbalances that occur in diseases other than FA.
|FA is caused by a severe deficiency of the frataxin protein inside cellular structures called mitochondria. Frataxin normally acts as a storage depot for iron.|
Friedreich's ataxia (FA) is caused by defects (mutations) in the gene for the protein frataxin. Genes are recipes for making proteins, which provide structure to our cells and drive the chemical reactions inside them. Scientists believe the frataxin protein regulates the levels of iron  inside mitochondria — tiny cellular "factories" that use oxygen to produce energy.
Iron is essential for this process, but if too much of it is left floating around freely inside mitochondria, it can trigger oxidative stress — the buildup of harmful oxygen-based free radicals.
Frataxin appears to act as a storage depot for iron, releasing it only when it’s needed. When frataxin is missing or defective, free iron accumulates in mitochondria, and oxidative stress damages the mitochondria.
Frataxin also provides the iron needed for synthesis of several key enzymes in the mitochondria. Therefore, a deficiency of frataxin results in a deficiency of these enzymes, further reducing mitochondrial function.
Mitochondria act as an essential energy source for nearly all of the cells in our bodies, which probably explains why FA affects cells of the nervous system, heart and sometimes other tissues.
FA doesn’t affect parts of the brain involved in mental functions; it mostly affects the spinal cord and the peripheral nerves that connect the spinal cord to the body’s muscles and sensory organs.
FA also affects the function of the cerebellum, a structure at the back of the brain that helps plan and coordinate movements.
|The peripheral nerves carry motor signals from the spinal cord to the body’s muscles. Muscle contraction creates sensations that are sent through the peripheral nerves to the spinal cord.|
When a person decides to move an arm, nerve cells in the brain send an electrical signal to the spinal cord, and the peripheral nerves pass the signal on to the arm muscles. And as the arm moves, the person can feel it moving because nerve cells send an electrical signal back through the peripheral nerves and up to the brain.
In FA, this flow of sensory information through the peripheral nerves and the spinal cord is severely affected. There’s also some impairment of muscle-controlling signals from the cerebellum and spinal cord.
Combined, these problems lead to the progressive losses of balance, coordination and muscle strength that characterize FA.
Upon hearing a diagnosis of FA, people often reasonably ask, “But it doesn’t run in our family, so how could it be genetic?”
The answer is that the mutations underlying FA can run silently through a family, because the disease is inherited in an autosomal recessive pattern.
Autosomal refers to the fact that the frataxin gene is on chromosome 9, one of the 22 pairs of autosomes (chromosomes other than the X or Y). Recessive means it takes two defective copies of the frataxin gene to cause FA, with one copy inherited from each parent, neither of whom would normally have FA symptoms.
Thus, FA might seem to occur “out of the blue,” but in reality, both parents are FA carriers, each silently harboring a mutation in frataxin. Many parents have no idea that they’re carriers of FA until they have a child who has the disease.
About one in 100 Americans is an FA carrier, but in some ethnic groups the frequency is higher. For example, about one in 70 people of Acadian (Cajun) ancestry is a carrier.
The most common type of mutation in the frataxin gene is called a trinucleotide repeat expansion. Spelled out in the four chemical "letters" that make up DNA, it looks like a stutter in the frataxin gene.
Normally, the gene contains five to 30 repeats of the three-letter chemical phrase "GAA," but in people with FA, the gene can contain hundreds of GAA repeats. Longer repeat expansions tend to cause an earlier onset and faster progression of FA, but the association isn’t strong enough to predict the course of FA in individual cases.
|People of Acadian ancestry, like this teen, may be at higher risk for FA.|
In more than 95 percent of people with FA, both copies of the frataxin gene contain expanded repeats. In the rest, just one copy of the frataxin gene is expanded and the other contains a single-letter change in the DNA code, called a point mutation.
In FA carriers, the frataxin gene can contain a repeat expansion, a point mutation or a premutation — a number of expanded repeats that’s just below the disease-causing range. In the germ line (ova and sperm), premutations might or might not expand into the disease-causing range, which makes it complicated for some carriers to determine their risks of passing on FA.
As a general rule, children with a biological sibling affected by FA have a 25 percent chance of developing the disease themselves.
|Scoliosis surgery involves using rods and screws to straighten and stabilize the spine.|
Treatments  for Friedreich's ataxia (FA) generally target specific symptoms rather than the disease itself.
Fortunately, FA’s most life-threatening symptom — heart disease  — can be controlled with treatments developed for use in heart conditions not related to FA.
For example, certain drugs (ACE inhibitors, diuretics and beta blockers) can decrease the workload of the heart, and pacemakers or medications can stabilize an arrhythmic heartbeat. Likewise, diabetes can be managed with insulin.
Surgical procedures can correct foot deformities and scoliosis.
One type of scoliosis surgery  is spinal fusion, which involves straightening the spine and then placing small pieces of bone over it, which grow together with the spinal bones and fuse them in place.
Although there’s no way to stop the progression of ataxia or muscle weakness in FA at this time, therapy can make it easier to cope with these problems.
Physical therapy  can help stretch tight muscles and enhance flexibility, and speech therapy can help re-train tongue and facial muscles to improve speech and swallowing . Your MDA clinic  can provide you with referrals to these specialists.
The discovery of frataxin and its roles in iron regulation and oxidative stress have raised the possibility of treatments  that might attack the underlying disease process in FA.
However, some experts recommend them, on the theory that the trials may not have been long enough or sensitive enough to show benefits.
Newer drugs that target the genetic defect in FA are in development.
To learn more about idebenone, read Idebenone trial yields slightly encouraging results in FA .
In the 1990s, the identification of mutations in the frataxin gene (from which frataxin protein is produced) as the underlying cause of Friedreich's ataxia opened the door to a much better understanding of FA and new avenues for treatment development. MDA funding led to the discovery of the frataxin gene.
Although two types of FA-causing mutations exist, by far the most common is a GAA trinucleotide repeat expansion — a region of DNA containing greater-than-normal numbers of the chemical phrase "GAA."
Five to 30 GAA repeats are within normal range, but in people with FA the GAA repeats number is in the hundreds , with the larger repeat expansions generally correlating with earlier onset and greater disease severity.
Approximately 96 percent of people with FA have two GAA repeat expansions, one on each chromosome. The other roughly 4 percent possess two different mutations: an expansion on one chromosome and a conventional gene mutation (most of which are truncations, or deletions) on the other.
Importantly, every individual with FA has at least one GAA expansion mutation, which has significance for therapy development.
Antioxidants  are designed to offer some protection against cell damage by chemicals known as free radicals and to enhance production of energy from cellular mitochondria.
The antioxidant idebenone  has been shown to be safe and well-tolerated in a number of clinical trials in FA. Unfortunately, benefits have been modest, at best.
Idebenone is similar to coenzyme Q10, a naturally occurring molecule. In 2010, a large-scale trial of idebenone in people with FA was conducted at several European centers but did not show benefit on neurological rating scales. A previous large-scale trial of idebenone in children with FA likewise did not show benefit. However, an earlier, phase 2 study, lasting six months and including 48 people, showed a statistical trend toward dose-related improvements in neurological function in those who received idebenone.
New antioxidant compounds are in development. In April 2011, Intellect Neurosciences said it wanted to develop its experimental antioxidant compound OX1 (Oxigon)  for FA.
Back to top 
In June 2011, Edison Pharmaceuticals announced preliminary results from a 28-day phase 2a clinical trial of its experimental compound EPI-A0001 in FA. Edison said there was significant improvement in neurological function  as assessed by the Friedreich's Ataxia Rating Scale in people who received the drug compared to those who received a placebo. The company said additional trials will be required to determine the safety and effectiveness of EPI-A0001. The drug is designed to improve energy production in mitochondria.
Back to top 
Frataxin production may be stimulated through the use of erythropoietin , a naturally occurring protein.
In 2010, an Austrian research team reported results of a small "proof-of-concept" trial in which 12 people with FA received erythropoietin injections three times a week for eight weeks. Eight of the 10 trial participants showed stable increases of frataxin levels, with individual increases ranging from 15 to 63 percent. Ataxia severity showed a 6 percent improvement in study participants.
Carbamylated erythropoietin, a derivative of erythropoietin, has been shown to increase frataxin levels in FA-affected cells without the unwanted added effect of stimulating blood-cell production, as erythropoietin does, making it a potential alternative for drug development for FA.
Back to top 
One approach to treating FA would be to supply functional frataxin genes or protein molecules to the person with FA through the insertion of functional genes to compensate for nonfunctional ones.
Various gene therapy-based strategies  hold the potential to benefit individuals with FA. Although it’s relatively early in the game, a limited number of studies in mice and human cells have yielded some encouraging results.
In a 2005 study, researchers used lentiviral or adeno-associated viral (AAV) vectors to carry the human frataxin gene into fibroblasts (cells that mature into a variety of connective tissue types) from FA patients. (A vector is a delivery vehicle for therapeutic genes.) Results included increased frataxin protein levels and a reduction in the treated cells’ sensitivity to oxidative stress.
A 2007 study analyzed the feasibility of gene insertion via the emptied-out shell of the herpes simplex virus type 1 (HSV-1), partnered with a stretch of DNA called an amplicon that helps the vector target a specific cell type. Results in FA-affected mice and human cells showed highly efficient DNA transfer and increased levels of frataxin production.
Similar positive results in 2007 came from a Spanish study in which mice were engineered so that researchers could eliminate, or “knock out,” frataxin activity specifically in motor neurons. The mice developed neurological symptoms after four weeks, but achieved full recovery in as few as four weeks after receiving injections of HSV-1 amplicon vectors carrying DNA that codes for human frataxin.
A Spanish study published in 2010 describes the successful use of artificial chromosomes and similar constructs called episomes to act as vectors for transporting genes to their targets.
Back to top 
The biotechnology company Repligen has received MDA support for development of an experimental treatment for FA known as histone deacetylase (HDAC) inhibition. HDAC inhibitors keep "read me" signals called acetyl groups on genes. Cells interpret these signals to mean that a gene is available to be "read" and used for protein production. HDAC inhibitors may make it possible to stimulate frataxin production  despite the presence of a mutation in the gene.
Back to top 
Iron chelation  — the trapping of harmful, unbound iron — is a possible therapy for FA. A 2008 study in research mice that didn't produce frataxin in their hearts showed that iron chelation significantly decreased iron levels in the heart and limited the harmful increase in the size of the cardiac muscle normally seen in frataxin-deficient mice.
An ongoing study to evaluate the effects of an iron chelator called deferiprone in people with FA in Europe may increase understanding of whether iron chelation should be part of an FA therapy regimen.
There is some evidence that combining an antioxidant with an iron chelator may be beneficial . A 20-person study for which results were announced in 2010 found that a combination of idebenone and deferiprone had a "stabilizing effect" on neurological function and reduced abnormal heart-muscle enlargement in people with FA who received the two-drug combination for 11 months.
Back to top 
Another approach to treating FA involves inserting new frataxin protein molecules. Recent research has shown that the frataxin protein can be modified  so that it can cross membranes and get to the right place in cells, the mitochondria.
Back to top 
A clinical trial is a test in humans of an experimental medication or therapy. Clinical trials are experiments, not treatments, and participation requires careful consideration.
Although it's possible to benefit from participating in a clinical trial, it's also possible that no benefit — or even harm — may occur. Keep your MDA clinic  doctor informed about any clinical trial participation. (Note that MDA has no ability to influence who is chosen to participate in a clinical trial.)
For more about clinical trials in general, see Learn About Clinical Studies , and to learn more about trial participation in neuromuscular disease, read the Quest magazine article Being a Co-Adventurer .
For a more refined list of FA clinical trials, visit ClinicalTrials.gov , a registry of federally and privately supported clinical trials in the United States and around the world. Select "Search for Clinical Trials," and follow the instructions to narrow down your search results.
|Michelle Moffitt Smith with her twins|
When I was about 14, I started having problems keeping my balance when standing or walking. After doctors did some tests, I found out I had Friedreich’s ataxia.
My parents and I immediately learned all we could about FA, with MDA’s help. There was no history of the disease in our family so it was a whole new world to us.
These pages have been prepared to help you deal with just that situation, by giving you much of the basic knowledge about FA that you’ll need as you or your child learns to live with this disease. You’ll find out that FA affects each person differently, and that, while it presents challenges in daily life, there are many techniques, technological devices and medical treatments to help you meet those challenges.
You’ll read here that FA doesn’t affect the intellect and doesn’t always take away the ability to walk. You’ll also read that some exciting new research  in FA may lead to the development of drugs to alleviate symptoms.
As I adjusted to being a teenager and a young woman with a disability, I learned a lot — not only about FA but about myself. I became more independent and learned to take charge of my education, my medical care and my other life experiences. Early in my years with FA, a doctor told me something that’s guided me ever since: He said you can’t use having a disability as an excuse for letting others make your decisions or for not pursuing your dreams.
Now, at 33, I am teaching psychology part time at three colleges and am the proud mother of healthy 5-year-old twins. Although it is difficult living independently, working, and taking care of a home and children, I am living proof it can be done with the help and support of family, friends and MDA. I met my husband, James Smith, through MDA’s Quest magazine. He also has a neuromuscular disease, and together we deal with our challenges and plan our future, just as any other couple does. We have been married now for nine years.
I know of many productive, successful people with FA — business leaders, outstanding students, engineers, active teens and bright kids, parents, even athletes. We’ve all learned to strike a balance between adapting to our limitations and surroundings, and living a fulfilling life despite them.
Besides my wonderfully supportive family and friends, I get tremendous help from the Muscular Dystrophy Association. MDA offers a great program of services, leads the world in Friedreich’s ataxia research and keeps us well informed about the disease. For more on MDA's services for individuals and families affected by SMA, see Help Through Services .
While MDA’s research program continues making strides toward better treatments and a cure, it’s good to know that people with disabilities have more opportunities than ever before to develop and use their abilities, and that the laws entitle us to equal employment opportunities and access to public places.
Through MDA, you’ll build a network of support. MDA’s Quest Magazine is filled with articles ranging from emergency room protocol, school issues, durable medical equipment and tips on buying a wheelchair-accessible van as well as the latest research news. At your local MDA clinic , expert doctors and health professionals will answer questions and make referrals to other specialists. At your MDA support group , you’ll make friends and find understanding.
Whatever challenges FA presents in your life, you can be sure that MDA and all its resources are there to help you and your family. You’re not alone.
Michelle Moffitt Smith
For more profiles of several people living with Friedreich's ataxia, see: