From the Guidelines
Friedreich ataxia is a rare genetic neurodegenerative disorder that requires a multidisciplinary approach to manage its symptoms and complications, with a focus on maintaining mobility, function, and quality of life. The disorder is characterized by progressive damage to the nervous system, resulting in movement problems, and is caused by mutations in the FXN gene, which leads to reduced production of frataxin protein essential for proper mitochondrial function 1. Symptoms typically begin between ages 5-15 and include progressive gait and limb ataxia, loss of coordination, muscle weakness, speech problems, scoliosis, foot deformities, and heart complications including cardiomyopathy.
Key Features of Friedreich Ataxia
- Inherited in an autosomal recessive manner with a prevalence of approximately 1 in 50,000 1
- Caused by a triplet repeat expansion mutation in the first intron of the gene encoding frataxin (FXN) 1
- Cardiac disease is the most life-threatening manifestation of FA, with mitochondrial dysfunction and severe oxidative stress despite normal levels of iron in blood 1
- Typical age of onset is 5 to 15 years, although later onset also occurs, with variable severity of phenotypic features 1
Management and Treatment
- Physical therapy helps maintain mobility and function, while occupational therapy assists with daily activities
- Cardiac medications may be prescribed for heart issues, and scoliosis might require bracing or surgery
- Speech therapy can address speech difficulties
- Recently, the FDA approved omaveloxolone (Skyclarys) as the first treatment specifically for Friedreich ataxia, which works by activating the Nrf2 pathway to improve mitochondrial function, highlighting the importance of staying updated with the latest treatment options
- Regular monitoring by a multidisciplinary team is essential, including cardiologists, neurologists, orthopedic specialists, and physical therapists to manage this progressive condition effectively.
From the Research
Overview of Friedreich Ataxia
- Friedreich ataxia is an autosomal recessive neurodegenerative disease characterized by impaired mitochondrial function and excessive production of free radicals 2.
- The disease leads to progressive damage to the nervous system and can cause a range of symptoms, including ataxia, dysarthria, and cardiac hypertrophy.
Idebenone Treatment
- Idebenone, a synthetic analogue of coenzyme Q, has been shown to be a powerful antioxidant that can improve cardiac hypertrophy and neurological symptoms in patients with Friedreich ataxia 3, 2.
- Studies have demonstrated that idebenone is well tolerated in both pediatric and adult patients, with most adverse events being gastrointestinal effects of mild to moderate severity 3, 2.
- High-dose idebenone treatment has been associated with improvement in neurological function and activities of daily living in patients with Friedreich ataxia, with a dose-dependent response observed in some studies 4.
Clinical Trials and Studies
- A randomized, double-blind, placebo-controlled trial found that high-dose idebenone treatment was generally well tolerated and associated with improvement in neurological function and activities of daily living in patients with Friedreich ataxia 4.
- An open-label trial found that idebenone treatment at early stages of the disease reduced the progression of cerebellar manifestations in patients with Friedreich ataxia 5.
- A study on the rehabilitation management of Friedreich ataxia found that task-oriented bimanual reaching activities, functional strengthening, and gait training using a walker featuring tension-controlled wheels and a reverse-braking system can improve gait performance and reduce falls in patients with the disease 6.
Mechanism of Action
- Idebenone influences the electron balance in mitochondria and acts as an anti-oxidant, preventing damage to the mitochondrial membrane, and as an electron carrier, supporting mitochondrial function and adenosine triphosphate (ATP) production 3.
- The antioxidant properties of idebenone may help to reduce oxidative DNA damage and improve mitochondrial function in patients with Friedreich ataxia 4.