From the Guidelines
Friedreich ataxia is a rare genetic neurodegenerative disorder that requires prompt management of its cardiac involvement to reduce morbidity and mortality, with treatment focusing on managing symptoms and complications, as stated in the American Heart Association scientific statement 1. The disorder is characterized by progressive damage to the nervous system, resulting in movement problems, impaired muscle coordination, and other complications. It is caused by mutations in the FXN gene, which leads to reduced production of frataxin protein essential for proper mitochondrial function. Some key features of Friedreich ataxia include:
- Progressive cerebellar dysfunction
- Ataxia
- Scoliosis
- Diabetes mellitus
- Impaired speech
- Loss of vision and hearing The severity of most phenotypic features of FA is variable, with typical age of onset between 5 to 15 years, although later onset also occurs. Cardiac disease is the most life-threatening manifestation of FA, and its management is crucial to improve quality of life and reduce mortality, as highlighted in the study published in Circulation 1. Treatment of Friedreich ataxia focuses on managing symptoms and complications, including physical therapy to maintain mobility and function, occupational therapy to assist with daily activities, and cardiac medications to address heart issues. Additionally, recent studies have led to the approval of omaveloxolone (Skyclarys) as the first treatment specifically for Friedreich ataxia, which works by activating the Nrf2 pathway to improve mitochondrial function, although this is not mentioned in the provided evidence 1. Regular monitoring by a multidisciplinary team is essential, as the condition is progressive with most patients requiring wheelchairs within 10-15 years of diagnosis and having a reduced life expectancy due to cardiac complications.
From the Research
Friedreich Ataxia Overview
- Friedreich ataxia is a neuro-degenerative disease causing limb and gait ataxia and hypertrophic cardiomyopathy 2
- It results from a triplet expansion in the first intron of the frataxin gene encoding a mitochondrial protein of yet unknown function 2
- The loss of frataxin is caused by a large GAA trinucleotide expansion in the first intron of the gene, resulting in deficiency of a Krebs cycle enzyme, aconitase, and of three mitochondrial respiratory chain complexes (I-III) 3
Idebenone Treatment
- Idebenone, a short-chain quinone, may act as a potent free radical scavenger protecting mitochondria against oxidative stress 2
- Idebenone has been shown to protect heart muscle against oxidative stress in some patients with Friedreich's ataxia 3
- Studies have demonstrated a positive effect of idebenone on cardiac hypertrophy in Friedreich's ataxia patients 3, 2, 4
- The optimal dosage of idebenone is still being evaluated, but most trials have used a dose of 5-10 mg/kg/day 3, 4
Cardiac Involvement
- Cardiac involvement is the most common cause of death (59%) in Friedreich's ataxia patients 5
- Cardiac-related death occurs at a significantly younger age than non-cardiac related death 5
- Idebenone treatment has been shown to reduce left ventricular mass and improve cardiac function in some patients with Friedreich's ataxia 3, 2
Multidisciplinary Clinical Care
- Friedreich's ataxia is a multisystem disorder requiring expertise from both pediatric and adult subspecialists to provide optimal management 6
- The phenotype of Friedreich's ataxia is unique, giving rise to specific loss of neuronal pathways, a unique form of cardiomyopathy, and diabetes incorporating components of both type I and type II disease 6
- Many agents are reaching Phase III trials, and if successful, these will provide a variety of new treatments for Friedreich's ataxia that will require many specialists to provide clinical therapy 6