Calcitriol, vitamin D supplement, boosts frataxin levels in small…

A low dose of calcitriol, an activated form of vitamin D used to help manage hypoparathyroidism and other disorders, led to statistically significant increases in frataxin protein levels among people with Friedreich’s ataxia in a small clinical trial conducted in Spain.

Although patients in the yearlong study did not report notable benefits in symptoms, researchers said they “cannot rule out that higher doses administered longer could yield neurological benefits,” urging further studies.

The findings were published in Movement Disorders, in a paper titled, “Calcitriol Treatment Is Safe and Increases Frataxin Levels in Friedreich Ataxia Patients.” The work was funded by Spain’s Ministry of Science and Innovation and by the Spain-based advocacy group Federación de Ataxias de España.

Friedreich’s ataxia is a genetic disorder in which mutations lead to abnormally low levels of the frataxin protein. Recent experiments in lab models have suggested that treatment with calcitriol can boost frataxin protein levels in cells. Spurred by this finding, a team of scientists conducted a pilot study to test the effects of calcitriol in people with Friedreich’s ataxia.

The study enrolled 20 patients, all of whom were set to take calcitriol at a dose of 0.25 micrograms (mcg) per day for one year. Four participants had late-onset disease, meaning their disease developed after age 25. The supplements were generally well tolerated; some patients reported mild, temporary side effects like headache or nausea.

Safety, tolerability highlighted

Five of the patients experienced abnormally high calcium levels while taking calcitriol, leading them to be discontinued from the study. None of these individuals experienced any symptoms related to their abnormal calcium levels, and in all cases calcium levels returned to normal after calcitriol was stopped.

“The minimal and manageable side effects, along with the reversible nature of hypercalcemia, highlight the drug’s safety and tolerability,” the researchers wrote.

For the 15 patients who completed a full year in the study, measures of neurological and motor function generally held steady or worsened somewhat after that year. Patient-reported measures of life quality also were generally unchanged. While the data don’t suggest a clear clinical benefit from calcitriol supplements, the researchers noted that “the treatment did not cause an exacerbation of neurological deterioration” in the patients, again highlighting its safety.

Frataxin protein levels, measured in platelets (cell fragments that help blood clot), showed a small but statistically significant increase after a year on calcitriol, from an average of 5.5 picogram/mcg to 7 mcg/picogram.

The findings lend credence to the idea that this form of vitamin D may offer benefits for Friedreich’s ataxia patients, though the researchers stressed that further studies will be needed to provide proof one way or the other. They called for future studies with more patients, longer follow-up times, and higher doses of calcitriol.

“A clinical trial with higher doses of calcitriol (eg, 0.50 mcg daily, which is still a normal dose), a larger patient cohort, and/or a more prolonged treatment can be considered for future interventions,” they wrote. “This would allow us to confirm if the increase in frataxin level is sustained and if it leads to a decline in disease progression after 1 year of treatment.”