What are the latest treatment options for Friedrich's ataxia (Friedreich's ataxia)?

Latest Treatment Options for Friedreich's Ataxia

The most effective treatment approach for Friedreich's ataxia (FA) involves a multidisciplinary management strategy focused on respiratory care, cardiac monitoring, and physical rehabilitation to improve quality of life and reduce mortality. 1

Disease Overview

• Friedreich's ataxia is an autosomal recessive neurodegenerative disorder caused by a GAA trinucleotide repeat expansion in the FXN gene, resulting in reduced frataxin protein levels 1
• The size of the GAA repeat expansion correlates with disease severity and age of onset 1
• Cardiac disease is the most life-threatening manifestation and the most frequent cause of death in FA 1

Cardiac Management

• Regular cardiac screening with ECG and echocardiography is essential as cardiac involvement is common and may be asymptomatic 1
• Standard heart failure therapies should be implemented for patients with cardiomyopathy according to established guidelines 1
• ICD therapy is recommended for secondary prevention in patients who have survived ventricular fibrillation or hemodynamically unstable ventricular tachycardia with LVEF ≤40% 1
• Primary prevention with ICD should follow standard guidelines for dilated cardiomyopathies 1
• Regular cardiac assessment is crucial due to the unpredictable progression of conduction abnormalities 1

Respiratory Management

• Regular assessments at least twice a year provide an impression of lung decline and allows for proactive early intervention 2
• Peak cough flow rate and forced vital capacity measurements are considered mainstays in clinical assessment of patients 2
• Regular airway clearance and measures to augment cough and mucociliary clearance are recommended 2
• Respiratory muscle strength training (RMST) has shown effectiveness in improving ventilatory pattern, lung volume, respiratory muscle strength, and quality of life domains in patients 2
• Cough assist devices have shown success in improving FVC, peak cough flow, and mid-expiratory flows in small studies 2
• Nebulized hypertonic saline or inhaled mannitol may be useful adjuncts to airway clearance in some patients 2
• Overnight polysomnography should be considered in adolescents with FA, particularly those with suspected sleep-related breathing abnormalities or progressive decline in lung function 2

Nutritional Management

• Assessment of the adequacy and safety of nutritional intake should be performed at least annually 2
• Supplemental calories by oral or enteral route should be provided for those with worsening nutritional status 2
• Early gastrostomy insertion should be considered in those with unsafe swallow or inadequate nutritional intake 2
• Gastrostomy placement is recommended when patients begin to present with progressive nutritional insufficiency, respiratory deterioration, and aspiration secondary to dysphagia that are unresponsive to conservative measures 2

Physical and Occupational Therapy

• Early and continued physiotherapy often mitigates the occurrence and effects of contractures and scoliosis 2
• Sequential occupational therapy treatments may contribute to limiting the progression of disability and maintaining participation in everyday activities 3
• Regular exercise, even in younger children who are still mobile, is advised to maintain function 2
• Rehabilitation therapy has shown to improve functional independence, though effects may not persist 12-24 weeks after treatment 4

Speech and Language Therapy

• Speech disturbances in FA have peculiar characteristics that progress along the disease course 5
• No specific validated treatments exist for speech disorders in FA, though tailored speech training or non-invasive neuromodulation appear as potentially reliable therapeutic options 5
• Assessment relies on multiple clinical scales, with instrumental investigations and novel technologies allowing more accurate measurements of speech parameters 5

Monitoring and Disease Management

• Regular screening for and treatment of diabetes mellitus is necessary 1
• Genetic testing is important for confirming diagnosis and identifying family members at risk 1
• Genetic counseling is recommended for families with a history of Friedreich's ataxia 1
• Multidisciplinary "one-stop" service provision by all subspecialties should be the target in this rare devastating illness 2

Emerging Treatments

• Multiple agents are reaching Phase III trials that may provide new treatment options for FA in the near future 6
• Progressive, diffuse lung disease that poorly responds to aggressive therapy should lead to consideration of non-infective causes including interstitial lung disease and pulmonary fibrosis, with early treatment with corticosteroids 2

Common Pitfalls to Avoid

• Delaying gastrostomy placement in patients with progressive dysphagia 2
• Overlooking cardiac involvement due to its sometimes asymptomatic nature 1
• Neglecting regular respiratory assessments which can lead to missed opportunities for early intervention 2
• Failing to provide multidisciplinary care coordination which is essential for comprehensive management 2