What is the treatment for Friedreich's ataxia?

Treatment for Friedreich's Ataxia

Currently, there are no approved disease-modifying therapies for Friedreich's ataxia (FA), and treatment focuses on managing symptoms, cardiac complications, and other manifestations of the disease to improve quality of life and reduce morbidity and mortality. 1, 2, 3

Disease Overview

• FA is an autosomal recessive neurodegenerative disorder caused by a GAA trinucleotide repeat expansion in the first intron of the FXN gene, resulting in reduced levels of frataxin protein 4
• Typical onset occurs around puberty with progressive ataxia, and life expectancy is 40-50 years 1
• Cardiac disease is the most life-threatening manifestation and the most frequent cause of death in FA 4

Cardiac Management

• Regular cardiac screening with ECG and echocardiography is essential as cardiac involvement is common and may be asymptomatic 4
• Standard heart failure therapies should be implemented for patients with cardiomyopathy according to established guidelines 4
• ICD therapy is recommended for secondary prevention in patients who have survived ventricular fibrillation or hemodynamically unstable ventricular tachycardia with LVEF ≤40% 4
• Primary prevention with ICD should follow standard guidelines for dilated cardiomyopathies 4

Neurological Management

• Physical therapy and rehabilitation are cornerstones of treatment to maintain function and prevent complications 1, 2
• Occupational therapy to assist with activities of daily living and adaptive equipment 1
• Speech therapy for dysarthria 1
• Management of spasticity with appropriate medications (baclofen, tizanidine) when indicated 2

Management of Other Manifestations

• Regular screening for and treatment of diabetes mellitus 4
• Orthopedic management of scoliosis and foot deformities 1
• Regular ophthalmologic evaluation for visual impairment 1

Emerging Therapies

• Several experimental approaches are under investigation but not yet approved:
  • Antioxidants like idebenone have shown some potential benefit for cardiac hypertrophy in open-label trials, though results from controlled trials have been mixed 1, 3
  • Therapies targeting increased FXN expression including histone deacetylase inhibitors and erythropoietin 1, 3
  • Iron chelators to address iron-mediated toxicity 1, 3
  • Gene and cell therapies are in development but not yet available for clinical use 5, 6

Genetic Counseling

• Genetic testing is important for confirming diagnosis and can help with identification of family members at risk 4
• The size of the GAA repeat expansion correlates with disease severity and age of onset 4

Clinical Monitoring

• Regular cardiac assessment with ECG and echocardiography to monitor for cardiomyopathy progression 4
• Neurological assessment to monitor disease progression 1
• Regular screening for diabetes and other metabolic complications 1

Important Considerations

• The undulating phenotype of cardiac involvement requires vigilant monitoring as the cardiomyopathy subtype may evolve over time 4
• Patients with FA are at risk for sudden cardiac death even with only mildly decreased left ventricular function 4
• Progression of conduction abnormalities may be unpredictable, requiring a low threshold for investigating symptoms or ECG findings 4

While research continues to advance toward potential disease-modifying therapies, current treatment focuses on symptom management, preventing complications, and addressing the cardiac manifestations that significantly impact mortality.