Friedreich's Ataxia
Friedreich’s Ataxia is a hereditary neurodegenerative disease characterized by progressive gait and limb ataxia, with multisystemic manifestations such as cardiomyopathy, diabetes, and hearing and visual impairments. It typically sets in during childhood or adolescence, predominantly affects populations of European ancestry, and follows a progressive course until the loss of independent ambulation.
The disease is of genetic origin, caused by mutations in the FXN gene that lead to reduced synthesis of the protein frataxin. This deficiency causes oxidative stress and neuronal degeneration, primarily in the central and peripheral nervous systems, as well as multisystemic dysfunctions including cardiomyopathy and diabetes.
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Progressive ataxia with postural instability and impaired motor coordination.
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Muscle weakness and spasticity.
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Loss of deep tendon reflexes and pyramidal signs.
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Speech articulation disorders (dysarthria) and swallowing difficulties (dysphagia).
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Systemic manifestations such as hypertrophic cardiomyopathy and diabetes mellitus.
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Neurological clinical evaluation with observation of ataxia and pyramidal signs.
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Genetic testing to identify mutations in the FXN gene.
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Electromyography and neurophysiological studies to assess peripheral neuropathy.
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Cardiological examinations (echocardiogram, electrocardiogram) to monitor cardiomyopathy.
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Muscle biopsy, rarely used for diagnosis.
Available therapies
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Rehabilitative support therapies to maintain mobility and coordination.
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Symptomatic pharmacological treatments to manage spasticity and cardiac disorders.
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Monitoring and treatment of cardiac and metabolic complications (e.g., diabetes).
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Experimental therapies under study, including gene and molecular therapies aimed at correcting the frataxin deficiency.
Research in progress
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Several clinical studies and trials are currently active for Friedreich’s Ataxia, focusing on disease-modifying therapies, including drugs to modulate oxidative stress, gene therapy approaches, and natural history studies.
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Trials with omaveloxolone (Skyclarys™), already approved, with long-term follow-up to evaluate its efficacy on motor progression and NRF2 pathways.
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Phase I/II studies on gene therapy for cardiomyopathy and increasing frataxin levels via AAV vectors.
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Global natural history studies and trials on etravirine/DT-216 for neuromuscular function.
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Reference laboratory
Contacts and informations
Prof. Yvan Torrente
yvan.torrente@policlinico.mi.it