Resveratrol is a natural substance found in small quantities in grapes, blueberries, cranberries, and highly concentrated in red wine. It is also available as a dietary supplement. It is now being tested as a potential treatment for Huntington’s disease.
How resveratrol works
Resveratrol directly or indirectly stimulates the activity of an enzyme called sirtuin type 1 ( SIRT1), which is known to upregulate key metabolic and anti-inflammatory pathways that protect cells from injury. How it does this is not clear, but resveratrol is thought to protect nerve cells in the brain due to its antioxidant activity. Anti-oxidants break down types of oxygen in the body that are toxic to cells.
A number of studies on blood flow in the brain and cognitive performance in humans provide evidence that resveratrol supplements can modulate brain functions, improving the utilization of glucose in energy production and promoting the relaxation of blood vessels.
Resveratrol is able to reach the brain to exert its beneficial effects, but it is broken down and removed from the body within a few hours after it is taken orally as a supplement.
Resveratrol also affects a number of other biological processes, including cell growth and differentiation, cell death, angiogenesis the (formation of new blood vessels), and metastasis (the spread of cancer) in ways that are not completely understood, and that is of less interest to researchers studying its potential benefit in Huntington’s.
A few studies have demonstrated the neuroprotective effects (protection of nerve cells from injury) in animal models of Huntington’s disease.
Resveratrol in clinical trials
A Phase 3 clinical trial (NCT02336633) expected to include 102 patients with Huntington’s, is currently recruiting participants in France. A total of 51 patients will receive 80 mg of resveratrol daily for one year and the remaining 51 will receive placebo.
The primary outcome is the degree of caudate atrophy, thought to be a sensitive marker of Huntington’s disease. Caudate atrophy is the wasting of the caudate nucleus, a part of the brain affected by Huntington’s. The atrophy or wasting of the caudate will be measured at the beginning and at the end of the study.
Secondary outcomes are a reduction in the progression of the disease, as measured by the Unified Huntington’s Disease Rating Scale, which measures motor control, cognitive symptoms, behavioral symptoms, independence, and a person’s ability to function in day-to-day life.
Total Functional Capacity, which assesses the ability to work, handle finances, perform domestic chores and self-care tasks, and live independently, will also be measured. The ratio of inorganic phosphate/phosphocreatine will be evaluated to assess normal brain activity. These tests will be done every three months for the duration of the study.
The trial is being conducted at the Institut du Cerveau et de la Moelle, Hôpital de la Pitié Salpêtrière in France. It is expected to be completed in January 2019.
Resveratrol has been the focus of media attention due to its potential benefit for several conditions, including coronary artery disease, obesity, and diabetes, and a few clinical trials have been conducted with patients who have these conditions.
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