Calcitriol Treatment Is Safe and Increases Frataxin Levels in Friedreich Ataxia Patients

Background Calcitriol, the active form of vitamin D (also known as 1,25‐dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich ataxia (FRDA). Objectives Based on these results, we aimed measuring the effects of a calcitriol dose of 0.25 mcg/24h in the neurological function and frataxin levels when administered to FRDA patients for a year. Methods 20 FRDA patients where recluted and 15 patients completed the treatment for a year. Evaluations of neurological function changes (SARA scale, 9‐HPT, 8‐MWT, PATA test) and quality of life (Barthel Scale and Short Form (36) Health Survey [SF‐36] quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non‐heterozygous sex and age matched controls. Results Although the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5.5 to 7.0 pg/μg after 12 months. Differences in frataxin levels referred to total protein levels were observed among sex‐ and age‐matched controls (18.1 pg/μg), relative controls (10.1 pg/μg), and FRDA patients (5.7 pg/μg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial. Conclusions Calcitriol dosage used (0.25 mcg/24 h) is safe for FRDA patients, and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.