Resveratrol
Resveratrol is a naturally occurring compound found in the skin of red grapes. Resveratrol has been investigated for activity to improve mitochondrial function and some studies suggest increased longevity, lowering glucose levels and anti-cancer activity in model systems. Researchers in Australia found that resveratrol also increased frataxin levels in laboratory studies. Investigators at MCRI evaluated the therapeutic potential of resveratrol in clinical trials. Jupiter Orphan Therapeutics attempted to develop a novel formulation of resveratrol to improve the absorption and pharmacokinetic properties.
INACTIVE: Stages of Development for Resveratrol
The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.
April 2011: FARA funded an open-label, pilot study of resveratrol at the University of Melbourne.
June 2013: The study team reported the results at the American Academy of Neurology in April and FARA’s Clinical Research Conference.
The primary objective of the study was to evaluate the safety, tolerability and efficacy of two different doses of resveratrol (1g and 5g). 27 subjects were enrolled and 24 completed the treatment for 12 weeks. Subjects were compared to baseline on primary and secondary outcome measures after the 12 weeks. The primary outcome measure of lymphocyte frataxin levels did not show a difference in either treatment group. Some of the secondary outcome measures, such as neurological rating scales and speech measures, showed improvement in the high dose group; this should be interpreted with caution as there was no placebo group. The high dose group that received 5 grams of resveratrol per day had significant gastrointestinal adverse events including diarrhea, loose stools and abdominal pain. The full results have been published, link is provided below.
January 2016: Jupiter and Murdoch announce a partnership to further advance development and testing of resveratrol as a treatment for FA. The product, JOT101, was a novel proprietary formulation developed by JOT utilizing the active ingredient of resveratrol. A new formulation that can more effectively deliver resveratrol and reduce side effects was necessary to fully evaluate the potential efficacy of resveratrol. (see Press Release below)
June 2016: Jupiter Orphan Therapeutics provided the FA community with an update on their work to develop, JOTROL™, an authentic resveratrol, in a proprietary, optimized and controlled delivery system. They shared data demonstrating improved bioavailability in animals which should result in lower resveratrol dosing to achieve efficacy.
A Phase 2 study, Micronised Resveratrol as a Treatment for FA, was held at 3 sites in Australia.
August 2021: At an FA community webinar, Dr. Delatycki reported that enrollment for the study was complete however the treatment phase extended into 2022. The study was a double-blinded, placebo-controlled randomised 2-period crossover trial of 2g/day of micronised resveratrol in FA over 24 weeks. The study enrolled 40 patients, >16 yrs of age with FA, from 3 sites. The primary outcome measure was the change in modified Friedreich Ataxia Rating Scale (mFARS) score from baseline to 24 weeks.
November 2022: The results of the Phase 2 study were presented at the International Congress for Ataxia Research (ICAR). Martin Delatycki, Murdoch Children’s Research Institute, the Principal Investigator of the study, stated that the study was negative, meaning reseveratrol provided no benefit relative to placebo.