Therapeutic intervention and management of Friedreich’s ataxia

Last updated April 8, 2024, by Lindsey Shapiro, PhD
Medically reviewed by David Lynch, MD, PhD

The management of Friedreich’s ataxia (FA) involves medications or interventions to manage symptoms and comorbidities, orthopedic surgery, and supportive interventions such as physical, occupational, and speech therapy. Skyclarys (omaveloxolone) is the only approved disease-modifying therapy for FA.

Disease-specific

Disease-modifying therapy

Skyclarys is a selective activator of antioxidant transcription factor nuclear factor erythroid 2-related (Nrf2), and an inhibitor of nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor.

Indication: Indicated in the U.S. for FA patients ages 16 and older. No contraindications, but the dose may need to be altered for patients being concomitantly treated with moderate or strong CYP3A4 inhibitors or inducers.

Dosing: Recommended dosage is 150 mg taken orally once daily on an empty stomach; adjustments sometimes necessary in cases of moderate to severe hepatic impairment or where CYP3A4 inhibitors are unavoidable.

Safety: Common side effects include elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain. Abnormalities in aminotransferases, B-type natriuretic peptide, and lipid parameters are possible and levels should be monitored periodically. Transaminase elevations and most other changes decline after the first few months. While there is no official data on decreasing the dose temporarily in response to side effects, it seems to be a logical plan (although benefit might also decrease transiently).

Orthopedic management

Conservative management of scoliosis should be considered to delay the need for surgery for as long as possible, especially in very young patients. Such approaches may include:

• bracing in ambulatory patients
• customized seating to limit progressive spinal deviations in non-ambulatory patients.

Where surgical correction is still indicated, posterior instrumented spinal fusion with pedicle screw fixation is recommended. Some nonambulatory patients may also require a fusion to the pelvis.

Ankle foot orthotics can help to improve stability, supporting joint alignment, improving range of motion, and facilitate function in FA patients with foot deformities, although surgical correction may eventually be indicated.

Cardiopulmonary testing is essential prior to any surgery to ensure that cardiac function will not be compromised intra- and post-operatively.

Dysphagia

Management of dysphagia may involve conservative interventions including:

• behavioral swallowing rehabilitation, including specific exercises
• neuromuscular electrical stimulation
• compensatory strategies, e.g., postural changes and education on mealtime behaviors
• dietary changes, such as using thickened fluids.

In advanced disease stages, alternate feeding routes, including nasogastric or gastrostomy tubes, may be necessary.

Symptomatic

Pain

Neuropathic pain in FA may be treated in the same way as that associated with other diseases, including the use of antiepileptic drugs, tricyclic antidepressant medications, and serotonin reuptake inhibitors, as well as topical agents such as lidocaine and capsaicin.

Non-neuropathic pain may be secondary to a range of other disease-related processes and thus, management strategies may vary. Intervention should be considered where quality of life is disturbed, with careful consideration of risks and benefits.

Sleep

General health measures such as sleep hygiene, regular physical activity, avoidance of alcohol, caffeine, and smoking, as well as body weight maintenance, are recommended for managing sleep issues in FA.

Restrictive lung disease and sleep disordered breathing (SBD) are managed with continuous positive airway pressure at night. Restless leg syndrome (RLS) responds to pharmacological treatment, with gabapentin and pregabalin being the preferred medications. Associated periodic limb movements in sleep may be treated with dopaminergic drugs. A review of current medications that may precipitate RLS is also indicated.

Spasticity

There is limited research on spasticity treatment in FA; guidelines for other diseases where spasticity is more common may be carefully applied. Physical therapy is initially recommended, followed by the addition of pharmacological treatment where spasticity remains uncontrolled.

Pharmacological approaches may include:

• injection of botulinum neurotoxin when spasticity is present in few select muscles
• oral medications such as baclofen, gabapentin, tizanidine, or clonazepam when spasticity is present in a number of muscles
• intrathecal baclofen or phenol injections where the above options are inadequate.

Fatigue

Managing other FA symptoms, including sleep issues, spasticity, and pain, can help to ease fatigue. Other potentially beneficial strategies include physical activity and behavioral management, such as mindfulness, relaxation, stress reduction, and cognitive behavioral therapy.

Supportive treatment

Physical therapy

Physical therapy and rehabilitation can benefit FA patients at all disease stages, helping to slow functional declines and ease fatigue or pain. Exercise regimens should be individualized to each patient with consideration of any medical contraindications.

High-intensity exercise (at least three days per week) is suggested for ambulatory patients and may include cardiovascular and endurance training, strengthening and stretching exercises. For nonambulatory patients, rehabilitation programs may include sitting and standing balance exercises, upper and lower limb strengthening, cardio-pulmonary exercise, and stretching.

Occupational therapy

Tailored occupational therapy can help FA patients maintain independence for as long as possible. This may include behavioral and coping mechanisms, environmental adaptations, and guidance on the use of digital and assistive technologies for mobility and communication.

Speech therapy

Virtually all FA patients become affected by dysarthria to some degree. Targeted intensive speech therapy, which may be individual or group-based, is designed to improve aspects of speech such as breath support, vocal control, and intelligibility.
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