Friedreich’s Ataxia Patients May Benefit from Low-dose Deferiprone Combined with Idebenone, Study Says

Low-dose deferiprone in combination with idebenone may improve both neurological and cardiological functions of patients with Friedreich’s ataxia. These are the findings of a study titled “Clinical Experience With Deferiprone Treatment for Friedreich Ataxia” published in the Journal of Child Neurology.

Friedrich’s ataxia is a progressive neurological disorder characterized by poor coordination, lack of reflexes, excessive muscle contraction, and loss of proprioceptive sensation. As the disease progresses, other problems could emerge, including diabetes, heart disease, and scoliosis.

The disease is caused by a mutation in the frataxin gene, which reduces the expression of the mitochondrial protein frataxin in both affected and unaffected tissues. This, in turn, induces iron buildup within the mitochondria leading to oxidative damage by promoting the formation of reactive oxygen species.

Two main approaches are used to repair defective mitochondria in FA patients. The first consists of the administration of coenzyme Q10 analog as an antioxidant and electron carrier through a daily dose of 5 mg/kg idebenone. This results in a minor decrease in oxidative stress and cardiac hypertrophy with no influence on neuromuscular function.

The other approach attempts to relieve the toxic effects of accumulated mitochondrial iron in FRDA cells, using iron chelators such as deferiprone (3-hydroxy-1, 2-dimethylpyridin-4-one). This drug is shown to yield improvements in cell function especially in animal models of FA, with dosage playing a key role.

Researchers examined a selected group of five FRDA patients treated with deferiprone 20 mg/ kg/day, in addition to idebenone-based therapy. Patients were followed for 10 to 24 months to understand the changes in neurological, cardiological, and laboratory blood parameters.

The results showed an overall increase in Friedreich’s Ataxia Rating Scale score, indicative of improvements in patients’ neurological function. Electrocardiography and echocardiography measurements showed that all patients were in sinus rhythm with minor abnormalities, demonstrating a normal electrical activity within patients’ heart.

Deferiprone caused no major blood damage in most subjects with the exception of a minor decrease in both white and red blood cell counts as well as in ferritin, a protein responsible for iron storage. The latter was spontaneously resolved upon dosage adjustment. Also, no side effects were noticed during the study except in two patients who discontinued deferiprone treatment.

The authors conclude that combined therapy of a low dose of deferiprone with idebenone is relatively safe, might improve neurological function, and seems to improve heart hypertrophy. Their findings warrant further studies, the authors said.