Early Genetic Testing Avoids Treatment Delays for Patients with Friedreich's Ataxia

Speakers during a symposium at The European Association of Neurology Congress called attention to delays in diagnosis and treatment of patients with Friedreich ataxia (FDRA), a rare, inherited neurodegenerative disorder and the most common hereditary ataxia.

Held in Finland in July 2024, the symposium was led by speakers Mathieu Anheim, M.D, Ph.D., professor of neurology at University Hospital of Strasbourg, and Jörg Schulz, M.D., professor of neurology at RWTH Aachen University Hospital. They urged for increased use of early genetic and biochemical testing for Friedreich ataxia as a way to decrease treatment delays.

Characterized by progressive neurodegeneration and multisystem complications, Friedreich’s ataxia results from expansions of the guanine-adenine-adenine triplet in the frataxin gene, leading to decreased levels of the protein frataxin. This deficiency contributes to ataxia, spasticity, pain, and cardiac problems. Generally, longer expansions are associated with earlier onset and faster disease progression.

The onset typically ranges from childhood, 8 to 14 years of age, to late adulthood. Recognizing signs and symptoms early is crucial to mitigating FRDA. Key neurological features of FRDA include ataxia, slurred speech, and the abolition of tendon reflexes. Extra-neurological manifestations may involve hypertrophic cardiomyopathy, scoliosis and diabetes.

The consensus among experts at the symposium was that genetic testing is crucial to differentiate FRDA from other ataxias, particularly in patients showing signs of cerebellar ataxia. Assessing biomarkers and utilizing brain imaging can also aid in diagnosis by helping physicians distinguish FRDA from other diseases with symptoms similar to FRDA.

The speakers stressed the importance of a timely diagnosis and referral to a specialist. Many patients experience significant delays in diagnosis, which often take years and involve multiple healthcare providers. Prompt referral to specialists is essential to improving patient outcomes and care. Because the prognosis may be poor, especially for those with early-onset FRDA, progression can be reasonably rapid. Patients should have a care plan in place as soon as possible so that they can live a more supported and comfortable life.

Management of FRDA requires a multidisciplinary approach, including physiotherapy, occupational therapy and possibly surgery for musculoskeletal issues. In 2022, best practice recommendations emphasized individualizing treatment based on patient symptoms and needs. Treatments include, but are not limited to, surgery, muscle relaxants, pain relief, botulinum toxin injections, and cognitive behavior therapy.

One therapy — Skyclarys (omaveloxolone) — is approved for FRDA-specific medication in the European Union and the United States for patients aged 16 years and older. Clinical trials have indicated that it can slow disease progression, especially if the omaveloxolone is started without delay.

The speakers concluded the symposium having discussed future directions. With the development of additional therapies in the pipeline, the landscape of FRDA treatment may broaden. Several other drugs currently in human trials may enhance mitochondrial function, reduce oxidative stress, or regulate frataxin-controlled metabolic pathways. While those drugs target the results of frataxin loss, gene therapies to act as frataxin replacements or increase frataxin-related gene expression are also in the works. 

Early recognition and diagnosis of FRDA, combined with a tailored treatment approach, are essential for improving the quality of life of affected patients and their families. Effective communication and coordination among healthcare providers are critical to ensuring comprehensive care for patients with FRDA.

Additional details from the symposium can be found at the European Medical Journal.