A Dozen Facts About Friedreich’s Ataxia

September 30, 2024

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Most people haven’t heard of the condition, but Friedreich’s ataxia is getting more attention because of a new treatment and a large number of clinical trials enrolling people with the condition.

It is named for Nicholas Friedreich, a German pathologist who described the condition in the 1860s and 1870s. According to an article about Friedreich published in the Journal of Neurochemistry in 2013, he wrote five long articles about a new spinal disease, but it was a short postscript to the fourth one that showed his insight into the disease that now carries his name.Friedreich received little recognition during his lifetime for his descriptions of what became known as Friedreich’s ataxia (FRDA).
Mutations in the frataxin gene on chromosome 9are the primary cause of FRDA. Frataxin is a protein that is essential for mitochondrial function and mitochondrial iron metabolism. The mutations arise from repeats of specific DNA sequences, guanine- adenine-adenine repeats, within the frataxin gene that causes a deficiency of frataxin. That shortage leads to the degeneration of nerve cells that adversely affects muscle coordination. The level of frataxin is related to the severity of the disease.
FRDA occurs with a frequency of approximately 1 in 30,000 to 1 in 50,000 in White individuals. It is one of the most common ataxias, the medical term for loss of muscle control
The guanine-adenine-adenine repeats that cause FRDA are found only in individuals of European, North African, Middle Eastern, or Indian origin. As a result, the prevalence of the disease is lowest in China, Japan and sub-Saharan Africa.
Diagnosing FRDA involves a complex, detailed neurological assessment and evaluation of family medical history. Tests designed to show whether there are mutations in frataxin gene are used to confirm the diagnosis.
The onset of FRDA typically occurs between the ages of 5 and 15. Usually the earlier the onset, the more severe disease. Early symptoms include difficulty with walking, maintaining balance and keeping coordinated. The rate of progression varies and may eventually entail scoliosis (sideways curvature of the spine), speech impairments and loss of limb sensation, further complicating daily tasks.
FRDA does not just affect the nervous system and muscles. Many individuals with FRDA develop hypertrophic cardiomyopathy, a condition that thickens the heart muscle, leading to cardiovascular complications. Diabetes can also occur in FRDA patients as a result of the condition.
FRDA shortens life expectancy and poses challenges to the quality of life of the people with the condition. Many of the people with FRDA experience complications that reduce their lifespan. Advances in medical management have improved the quality of life for many living with FRDA and some people with the condition survive into their late 40s or early 50s.
Skyclarys (omaveloxolone) is the first and only FDA-approved drug to treat FRDA in the U.S. The drug regulator announced the approval on Feb. 28, 2023. The FDA-approved label for Skyclarys (pronounced sky-CLARE-is) says that the “precise mechanism by which omaveloxolone exerts its therapeutic effect in patients with Friedreich’s ataxia is unknown.” The label goes on to say that omaveloxolone activates a nuclear factor pathway that is involved in the cellular response to oxidative stress.
Reata Pharmaceuticals, headquartered in Plano, Texas, developed Skyclarys and shepherded it through the FDA approval process. Biogen, the Cambridge, Massachusetts, biotech giant announced in July 2023 that it was acquiring Reata for $7.3 billion.
When Skyclarys was approved, Reata said the whole sale acquisition price — the list price — would be $370,000 for a year’s worth of treatment
FRDA is a hot item in research articles. ClinicalTrials.gov currently lists approximately 80 trials involving people with FRDA.