Calcitriol treatment is safe and increases frataxin levels in Friedreich Ataxia patients

Abstract

BackgroundCalcitriol, 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).MethodsBased on these results, we started a pilot clinical trial in which a dose of 0.25mcg/24h was administered to 15 FRDA patients for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and 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.ResultsAlthough the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5,6 pg/μg, to 7,0 pg/μg after 12 months. Differences in frataxin levels referred to total protein amounts were observed amongst sex and age matched controls (18.11 pg/μg), relative controls (10.07 pg/μg), and FRDA patients (5.71 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.ConclusionCalcitriol dosage used (0.25mcg/24h) is safe for FRDA patients and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits.