Triheptanoin improves brain energy metabolism in patients with Huntington disease.

Abstract

OBJECTIVE:

Based on our previous work in Huntington disease (HD) showing improved energy metabolism in muscle by providing substrates to the Krebs cycle, we wished to obtain a proof-of-concept of the therapeutic benefit of triheptanoin using a functional biomarker of brain energy metabolism validated in HD.

METHODS:

We performed an open-label study using (31)P brain magnetic resonance spectroscopy (MRS) to measure the levels of phosphocreatine (PCr) and inorganic phosphate (Pi) before (rest), during (activation), and after (recovery) a visual stimulus. We performed (31)P brain MRS in 10 patients at an early stage of HD and 13 controls. Patients with HD were then treated for 1 month with triheptanoin after which they returned for follow-up including (31)P brain MRS scan.

RESULTS:

At baseline, we confirmed an increase in Pi/PCr ratio during brain activation in controls-reflecting increased adenosine triphosphate synthesis-followed by a return to baseline levels during recovery (p = 0.013). In patients with HD, we validated the existence of an abnormal brain energy profile as previously reported. After 1 month, this profile remained abnormal in patients with HD who did not receive treatment. Conversely, the MRS profile was improved in patients with HD treated with triheptanoin for 1 month with the restoration of an increased Pi/PCr ratio during visual stimulation (p = 0.005).

CONCLUSION:

This study suggests that triheptanoin is able to correct the bioenergetic profile in the brain of patients with HD at an early stage of the disease.

CLASSIFICATION OF EVIDENCE:

This study provides Class III evidence that, for patients with HD, treatment with triheptanoin for 1 month restores an increased MRS Pi/PCr ratio during visual stimulation.

• Authors: Isaac Mawusi Adanyeguh, Daisy Rinaldi, Pierre-Gilles Henry, Samantha Caillet, Romain Valabregue, Alexandra Durr, Fanny Mochel
• Journal: Neurology (Neurology) Vol. 84 Issue 5 Pg. 490-5 (Feb 03 2015) ISSN: 1526-632X [Electronic] United States
• PMID: 25568297 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Academy of Neurology.

Chemical References

• Triglycerides
• triheptanoin

Topics

• Adult
• Brain (drug effects, metabolism)
• Energy Metabolism (drug effects, physiology)
• Female
• Humans
• Huntington Disease (drug therapy, metabolism)
• Magnetic Resonance Spectroscopy (methods)
• Male
• Middle Aged
• Triglycerides (pharmacology, therapeutic use)
• Young Adult