What is the best treatment approach for a young patient with Friedreich's ataxia?

Friedreich Ataxia Treatment Approach

The best treatment for a young patient with Friedreich's ataxia is omaveloxolone (Skyclarys), the only FDA-approved disease-modifying therapy, combined with intensive multidisciplinary rehabilitation including respiratory muscle strength training, early nutritional intervention with proactive gastrostomy placement, and cardiac monitoring with standard heart failure therapies. 1, 2

Disease-Modifying Pharmacotherapy

Omaveloxolone (Skyclarys) is the only FDA-approved medication for Friedreich's ataxia and should be initiated in eligible patients. 1 This Nrf2 activator addresses the underlying mitochondrial dysfunction caused by frataxin deficiency, though it is not curative and is well-tolerated. 1

• Idebenone may provide benefit specifically for cardiac hypertrophy, though evidence is more limited than for omaveloxolone. 3
• Gene therapy, protein replacement, and epigenetic approaches represent the most promising future prospects for enduring disease modification. 1

Respiratory Management

Implement respiratory muscle strength training (RMST) immediately, as it improves ventilatory pattern, lung volume, respiratory muscle strength, and quality of life. 2 This is critical because respiratory complications are a leading cause of premature death in ataxia patients. 4

• Perform spirometry assessments at least twice yearly, measuring peak cough flow rate and forced vital capacity as mainstays of monitoring. 2
• Use cough assist devices to improve FVC, peak cough flow, and mid-expiratory flows. 2
• Add nebulized hypertonic saline or inhaled mannitol as adjuncts to airway clearance. 2
• Order overnight polysomnography in adolescents with suspected sleep-related breathing abnormalities or progressive lung function decline. 2

Nutritional Management

Assess nutritional intake and swallowing safety annually, and place gastrostomy early when dysphagia, aspiration, or nutritional insufficiency develops. 2 Do not delay gastrostomy placement—this is a critical pitfall that worsens outcomes. 2

• Provide supplemental calories by oral or enteral route for worsening nutritional status. 2
• Place gastrostomy when progressive nutritional insufficiency, respiratory deterioration, or aspiration secondary to dysphagia occurs and is unresponsive to dietary modifications. 2
• Perform videofluoroscopic swallow study (VFSS) as the gold standard for assessing pharyngeal phase swallowing abnormalities. 5

Cardiac Management

Screen with ECG and echocardiography regularly, as cardiac disease is the most life-threatening manifestation and most frequent cause of death in Friedreich's ataxia. 2 Patients are at risk for sudden cardiac death even with only mildly decreased left ventricular function. 2

• Implement standard heart failure therapies according to American College of Cardiology guidelines for patients with cardiomyopathy. 2
• Place ICD for secondary prevention in patients who survive ventricular fibrillation or hemodynamically unstable ventricular tachycardia with LVEF ≤40%. 2
• Consider primary prevention ICD following standard dilated cardiomyopathy guidelines. 2
• Maintain a low threshold for investigating symptoms or ECG findings, as progression of conduction abnormalities is unpredictable. 2

Physical and Occupational Therapy

Initiate early and continued physiotherapy to mitigate contractures and scoliosis, with regular exercise to maintain function. 2 Evidence shows inpatient rehabilitation reverses functional decline in Friedreich's ataxia patients, with gains sustained post-discharge. 6

• Prescribe balance training programs for poor balance, low balance confidence, and fear of falls. 5
• Implement postural training to improve trunk control. 5
• Use task-oriented upper limb training to improve reaching speed and reduce trunk motion. 5
• Fit patients with appropriate assistive devices (canes, ankle-foot orthoses) to significantly improve balance and mobility. 5
• Progress to more challenging training activities throughout rehabilitation for continued improvement. 5

Multidisciplinary Coordination

Establish "one-stop" multidisciplinary service provision with all subspecialties, as this is the target standard for this devastating illness. 2 Regular monitoring under multidisciplinary expertise is essential. 5

Critical Pitfalls to Avoid

• Delaying gastrostomy placement in patients with progressive dysphagia leads to worsening respiratory status and nutritional decline. 2
• Neglecting regular respiratory assessments (at least twice yearly) misses opportunities for early intervention before irreversible decline. 2
• Underestimating cardiac risk in patients with only mild left ventricular dysfunction—sudden cardiac death can occur even with minimal functional impairment. 2
• Failing to provide coordinated multidisciplinary care, which is essential for comprehensive management of this multi-system disease. 2