It aims to treat brain energy deficits by improving brain metabolism in Huntington’s disease patients.
How Triheptanoin works
The brain consumes glucose as a source of energy. In Huntington’s disease, glucose consumption is decreased in brain areas affected by the disease, like the cerebral cortex (the outer layer of gray matter) and the basal ganglia (a cluster of neurons deep beneath the cerebral cortex). The activity of mitochondria, structures in the cell that produce energy using glucose, is also lower.
Triheptanoin is a triglyceride, a kind of fat, that is artificially produced. It is almost flavorless and colorless, and is used as medical food to treat certain metabolic disorders or disorders involving the body’s energy production.
Triheptanoin is thought to have an anaplerotic role, meaning that it can replenish substances involved in the tricarbolic acid cycle, a pathway used by cells to produce energy, providing an alternative source of energy to the brain.
Triheptanoin in clinical trials
A pilot clinical trial (NCT01882062) assessed the effect of triheptanoin on energy metabolism in the brains of 10 early-stage Huntington’s patients and 13 healthy volunteers. Markers of increased adenosine triphosphate synthesis (adenosine triphosphate is an energy “currency” that transfers energy in cells) were measured before, during, and after being exposed to a visual stimulation. Researchers used magnetic resonance spectroscopy (MRS, a non-invasive technique used to measure changes in brain chemistry, also called NMR) to make these measurements.
Trial results, published in the scientific journal Neurology, showed that after one month of triheptanoin use (triheptanoin oil given at mealtime at dose of 1g/kg of weight each day), the level of energy production in the brain during visual stimulation had become normal in Huntington’s patients. These findings, Inserm reported in 2015, indicated a potential for the use of triheptanoin to treat brain energy deficits in Huntington’s.
A Phase 2 clinical trial (NCT02453061) of triheptanoin, called TRIHEP3, is currently recruiting an estimated 100 participants with early Huntington’s disease having a Unified Huntington’s Disease Rating Scale (UHDRS) score between 5 and 40. UHDRS assesses clinical features and course of the disease.
The trial is a randomized, double-blind, controlled study taking place at one center each in France and the Netherlands, and treated patients will be given triheptanoin oil at 1g/kg of body weight daily for six months, followed by an open-label and six-month extension study. Its primary outcomes are an increase in brain energy restoration and a decrease in the rate of caudate atrophy, a common brain feature of Huntington’s that worsens over time. The caudate nucleus is part of the basal ganglia.
Extensive testing at 6 and 12 months will include motor, psychiatric, and cognitive assessments as well as patient autonomy evaluations. The safety and tolerability of the treatment will also be monitored.
This study is being conducted by the Institut National de la Santé Et de la Recherche Médicale, France, in collaboration with Ultragenyx. Enrollment information is available by clicking on its clinical trial identification number.
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