Friedreich Ataxia (FA)

Friedreich ataxia (FA) is a rare, inherited, neurodegenerative disease characterized by progressive atrophy of specific regions within the brain, including the cerebellum, the spinal cord, and peripheral nerves. Clinically, this manifests in the degeneration of muscle coordination and strength, muscle spasticity, sensory deficits, problems with balance and proprioception, and gait difficulties.¹

There is no curative treatment for FA; however, pharmacological, physical, occupational, and speech therapies, along with surgery are used to manage the symptoms and disease-related complications of FA.

Pharmacological Management

Friedreich ataxia is caused by mutations in the FXN gene, which result in deficiencies in the protein frataxin. Frataxin insufficiency causes problems with iron metabolism within the mitochondria. Increased accumulation and deposition of iron increases oxidative stress and free radicals, contributing to FA disease pathology.² 

Antioxidant Treatments

The use of antioxidants may help reduce oxidative stress in patients with FA. The most commonly used antioxidants used to treat FA include coenzyme Q10, vitamin E, idebenone, N-acetylcysteine, selegiline, dehydroepiandrosterone, alpha-tocopheryl quinine EPI-A0001, and pioglitazone.³

Read more about FA therapies

Nonantioxidant Treatments

Nonantioxidant treatments that have been studied include³: 

• Ferriprox® (Deferiprone), an iron chelator, which is suggested to work by redistributing excess iron accumulated in mitochondrial compartments to the cytosol
• Erythropoietin, which works by significantly increasing frataxin expression throughout many cells, including lymphocytes in patients with FA
• Histone deacetylase inhibitors, which increase frataxin levels and revert FXN gene silencing
• Resveratrol, which increases frataxin levels in cell and mouse models of FA
• Actimmune® (interferon gamma-1b), which increases frataxin expression in dorsal root ganglion neurons in murine models of FA.

Neurontin® (gabapentin), Lyrica® (pregabalin), Elavil® (amitriptyline), Cymbalta® (duloxetine), and Lamictal® (lamotrigine) are medications that may treat neuropathic pain in patients with FA. If nonpharmacological methods, such as physical therapy, are unsuccessful in treating spasticity and muscle spasms, pharmacological treatments for spasticity and spasms include Lioresal® (baclofen), benzodiazepines such as Valium®, Xanax®, and Ativan®, Dantrium® (dantrolene), Zanaflex® (tizanidine), Neurontin® (gabapentin), Botox® (botulinum toxin) injections, and alcohol and phenol injections.⁴

Read more about FA experimental therapies

Botox Injections

The best clinical practice guidelines published in 2022 recommend against the use of Botox injections for the specific management of upper limb function in individuals with FA experiencing spasms and spasticity. However, Botox injections are recommended to manage localized areas of spasticity following a risk-benefit analysis and failure of conservative treatments such as physical therapy.⁵

For patients with FA who are still ambulatory, a risk-benefit analysis of Botox injections should be performed to assess potential risks or benefits related to the individual’s ambulation, dynamic standing balance, and ability to participate in physical therapy. For patients with FA who are no longer ambulatory, Botox injections are conditionally recommended in combination with stretching and ankle-foot orthotics for patients with spasticity and reduced gastrocnemius/soleus muscle length.⁵

Intradetrusor Botox injections may also be considered for treating overactive bladder symptoms and urinary incontinence.⁵

Read more about FA complications

Physical Therapy

Physical therapy rehabilitation techniques focus on strategies and compensatory techniques to enable patients with FA to remain ambulatory and participate in daily activities for as long as possible.⁶ Aerobic conditioning for 20 to 25 minutes at 70% to 85% maximum heart rate using a stationary cycle has been shown to improve aerobic fitness in patients with FA.^6,7 Physical therapists can identify adaptive exercise programs including community fitness and recreational activities that best fit the needs and capabilities of patients with FA given their individual impairments.⁶

Physical therapists can also help patients with FA to maintain optimal biomechanical alignment, especially pertaining to the spine and feet, which are prone to developing neuromuscular imbalances, leading to scoliosis and foot deformities. Performing daily range of motion exercises to improve muscle length and soft tissue extensibility allows for improved alignment and maintenance of the capacity for weight-bearing and mobility.⁶

Physical therapists also assist with the decision-making process regarding the use of assistive or adaptive devices, such as orthotics, canes, or walkers, to enable patients with FA to maintain independence and mobility.⁶ The use of a reverse-brake-system walker reduces fall frequency to allow patients to maintain independent gait.^6,8 When patients with FA become nonambulatory, physical therapists can assist with wheelchair customization, fitting, and training. This improves trunk control while seated and may help prevent the progression of scoliosis. They also can help patients decide whether a manual wheelchair or power wheelchair is needed depending on their upper extremity coordination and strength.⁶

Conventional physical therapy interventions also comprise one of the main focuses of physical therapy programs for patients with FA.⁹ Helpful exercises may consist of static and dynamic balance, whole-body movements for trunk-limb coordination, strategies to prevent falls and injury, gait training exercises to improve postural control and walking speed, and targeted exercises to reduce the development of contractures or treat them.¹⁰

Another unique treatment method to improve dexterity, coordination, and balance involves the use of video gaming (such as the Nintendo Wii or Xbox Kinect) or computer-assisted training for ataxia.⁹ These methods target specific impairments in this patient population while keeping young patients with FA engaged.

Read more about FA care team

Occupational Therapy

Occupational therapists help patients manage task performance. They work with patients to improve their skills or help them discover and learn compensatory strategies to complete difficult tasks. These strategies and skills allow patients with FA to maintain their independence and participate in activities of daily living while limiting the progression of disability through the stabilization of neurological deficits.¹¹ 

Speech Therapy

Speech therapy focuses on the management of dysarthria, which is a common impairment among individuals with FA. 

According to a systematic review of the literature published in 2014, most studies (13 of 14) analyzed the efficacy of pharmacological treatments against placebo in improving speech production among patients with degenerative cerebellar ataxias, while the remaining study assessed nonspecific physical therapy and occupational therapy treatment in an inpatient hospital. No studies evaluated traditional speech therapies, suggesting insufficient and low-quality evidence for treatments designed to treat speech disorders in patients with hereditary ataxias.¹² 

Gene Therapy

While gene replacement therapy is not currently an available treatment option, this potential future treatment is under exploration for those living with FA. Gene therapy may correct the frataxin insufficiency due to FXN gene mutations.¹⁰

Read more about FA genetics

Surgery 

Several surgical procedures can help manage disease-related complications, including^13-15:

• Placement of an internal cardiac defibrillator or heart transplantation to treat cardiac arrhythmias, hypertrophic cardiomyopathy, and heart failure
• Spinal surgery for severe scoliosis, if indicated
• Placement of a feeding tube for patients with FA who have severe dysphagia
• Placement of an intrathecal baclofen pump for patients with FA who have spasticity and painful muscle spasms.

Read more about FA surgical management

References

1. Friedreich’s ataxia. Johns Hopkins Medicine. Accessed January 20, 2023.
2. Lupoli F, Vannocci T, Longo G, Niccolai N, Pastore A. The role of oxidative stress in Friedreich’s ataxia. FEBS Lett. 2018;592(5):718-727. doi:10.1002/1873-3468.12928
3. Kearney M, Orrell RW, Fahey M, Brassington R, Pandolfo M. Pharmacological treatments for Friedreich ataxia. Cochrane Database Syst Rev. 2016;8:CD007791. doi:10.1002/14651858.CD007791.pub4
4. Corben LA, Lynch D, Pandolfo M, Schulz JB, Delatycki MB. Consensus clinical management guidelines for Friedreich ataxia. Orphanet J Rare Dis. 2014;9:184. doi:10.1186/s13023-014-0184-7
5. Corben LA, Collins V, Milne S, et al; Clinical Management Guidelines Writing Group. Clinical management guidelines for Friedreich ataxia: best practice in rare diseases. Orphanet J Rare Dis. 2022;17:415. doi:10.1186/s13023-022-02568-3
6. Maring JR, Croarkin E. Presentation and progression of Friedreich ataxia and implications for physical therapist examination. Phys Ther. 2007;87(12):1687-1696. doi:10.2522/ptj.20060232
7. Fillyaw MJ, Ades PA. Endurance exercise training in Friedreich ataxia. Arch Phys Med Rehabil. 1989;70(10):786-788. 
8. Harris-Love MO, Siegel KL, Paul SM, Benson K. Rehabilitation management of Friedreich ataxia: lower extremity force-control variability and gait performance. Neurorehabil Neural Repair. 2004;18(2):117-124. doi:10.1177/0888439004267241
9. Hartley H, Cassidy E, Bunn L, et al. Exercise and physical therapy interventions for children with ataxia: a systematic review. Cerebellum. 2019;18(5):951-968. doi:10.1007/s12311-019-01063-z
10. Tai G, Corben LA, Yiu EM, Milne SC, Delatycki MB. Progress in the treatment of Friedreich ataxia. Neurol Neurochir Pol. 2018;52(2):129-139. doi:10.1016/j.pjnns.2018.02.003
11. Ciancarelli I, Cofini V, Carolei A. [Disability and occupational therapy in patients with Friedreich’s ataxia]. G Ital Med Lav Ergon. 2011;33(2):201-204. Italian.
12. Vogel AP, Folker J, Poole ML. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes. Cochrane Database Syst Rev. 2014;10:CD008953. doi:10.1002/14651858.CD008953.pub2
13. Williams CT, De Jesus O. Friedreich ataxia. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated September 5, 2022. Accessed January 20, 2023. 
14. Vogel AP, Keage MJ, Johansson K, Schalling E. Treatment for dysphagia (swallowing difficulties) in hereditary ataxia. Cochrane Database Syst Rev. 2015;11:CD010169. doi:10.1002/14651858.CD010169.pub2
15. Kalyvas AV, Drosos E, Korfias S, Gatzonis S, Themistocleous M, Sakas DE. Intrathecal baclofen therapy for painful muscle spasms in a patient with Friedreich’s ataxia. Stereotact Funct Neurosurg. 2018;96(2):127-130. doi:10.1159/000489220

Reviewed by Kyle Habet, MD, on 1/23/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.