What is FA?

Friedreich’s ataxia (FA) is a debilitating, life-shortening, degenerative neuro-muscular disorder. About one in 50,000 people in the United States has Friedreich's ataxia. It is estimated there are 4,000 individuals affected with FA in the U.S., and 15,000 affected individuals worldwide.

Learn more about FA

Most individuals have onset of symptoms of FA  between the ages of 5 and 18 years. Adult or late onset FA is less common, <25% of diagnosed individuals, and can occur anytime during adulthood. FARA is supporting research that will improve the quality and length of life for those diagnosed with Friedreich's ataxia and will lead to treatments that eliminate its symptoms.

The Signs & Symptoms of Friedreich's Ataxia are:

  • loss of coordination (ataxia) in the arms and legs
  • fatigue - energy deprivation and muscle loss
  • vision impairment, hearing loss, and slurred speech
  • aggressive scoliosis (curvature of the spine)
  • diabetes mellitus (insulin - dependent, in most cases)
  • serious heart conditions, including  hypertrophic cardiomyopathy and arrthymias

These symptoms are not present in all individuals with FA, for example diabetes occurs in about 10-20% of individuals with FA. The intellectual capabilities of people with Friedreich's ataxia remain completely intact. The progressive loss of coordination and muscle strength leads to muscle incapacitation and the eventual full-time use of a wheelchair. Most young people diagnosed with FA require mobility aids such as a cane, walker, or wheelchair by their teens or early 20s.

Genetic testing analyzes the FXN gene, which is the only gene identified to cause Friedreich's ataxia.

Positive genetic test results for Friedreich’s ataxia usually contain two numbers that indicate presence of the disease. What do these numbers mean? Our genetic code is spelled out along the double helix of our DNA by triplet combinations of four nucleotides labeled A, T, C, and G. At the key place in the FXN gene of a person not affected with the disease, only a dozen or so triplet combinations of the nucleotides GAA would be found. In a person affected with FA; however, this combination of the GAA nucleotides is usually repeated hundreds of times, making it very difficult for the normal part of the gene to be read or "transcribed"; thus, limiting the amount of frataxin protein that can be encoded and formed. {Please see the information under the tab “Effect of genetic mutations” for an explanation on how the GAA repeat expansion silences the FXN gene}

For FA, in 96% of affected individuals, the two FXN gene alleles have GAA triplet repeat expansions that silence expression of the gene, preventing enough frataxin protein made for function in the mitochondria. The two numbers in the genetic test reports refer to the number of GAA triplet repeats on each allele copy of the FXN gene. One number is associated with the allele (gene) inherited from mom and the other number is associated with the allele (gene) inherited from dad. The expanded numbers of the GAA triplet repeats confirm the inheritance of Friedreich's ataxia. Research seems to indicate general correlation between some FA symptoms and the numbers of GAA repeats.

In ~4% of people affected with Friedreich’s ataxia, the genetic test report includes one allele of the FXN gene with a GAA triplet repeat expansion and the other allele with a single nucleotide change, called a point mutation, or a deletion in the FXN gene. Changing a nucleotide of A, T, C or G to another nucleotide often causes a change in the frataxin protein structure; thus, causing a change in frataxin’s ability to execute its function. A gene deletion removes a section of nucleotides, which can also result in loss of FXN gene expression and frataxin protein function.

The effect of genetic mutations

FA is an inherited or single gene disorder.  Mutations or DNA changes in the FXN gene cause FA.

FA is inherited in an autosomal recessive manner, meaning that individuals with FA have two mutated or abnormal copies of the FXN gene, this means both biological parents must be a carrier of the disease for a child to be affected.  It is estimated that 1 in 100 people are carriers, and carriers do not exhibit symptoms of FA.  Each such carrier parent has one mutated gene (allele) and one normal gene (allele) in the FXN gene.  Because each child gets one of the mother’s genes and one of the father’s genes in this location, there are four possible combinations of the genes passed down to the child or a 25% chance that the child will have FA.

The FA  gene mutation  limits the production of a protein called frataxin. Frataxin is known to be an important protein that functions in the mitochondria (the energy producing factories) of the cell. Frataxin helps to move iron and is involved with the formation of iron-sulfur clusters, which are necessary components in the function of the mitochondria and thus energy production. We also know that specific nerve cells (neurons) degenerate in people with FA, and this is directly manifested in the symptoms of the disease.

The Treatment for Friedreich's Ataxia

FARA is funding research to find treatments and a cure. We believe the treatment era for FA is now! As a result of great advancements to understand the cause of the disease, new treatments are now emerging. These treatments address the causes of FA such as gene mutation, frataxin production, iron sulfur clusters, and mitochondrial function. A full listing of treatment initiatives can be viewed in FARA’s treatment pipeline. Several of these treatments are  in clinical trials which require patient participation.

The first drug to treat FA, SKYCLARYS (omaveloxolone), was approved by the FDA in February 2023 for people who have FA and are 16 years or older. Clinical trials for SKYLCARYS showed improvement in neurological symptoms and slowing of disease progression compared to placebo groups.

In addition, people with FA are supported by a diverse clinical care team, often including neurologists, cardiologists, and endocrinologists, to monitor and manage symptoms.