PT  - JOURNAL ARTICLE
AU  - Isaac Mawusi Adanyeguh
AU  - Daisy Rinaldi
AU  - Pierre-Gilles Henry
AU  - Samantha Caillet
AU  - Romain Valabregue
AU  - Alexandra Durr
AU  - Fanny Mochel
TI  - Triheptanoin improves brain energy metabolism in patients with Huntington disease
AID  - 10.1212/WNL.0000000000001214
DP  - 2015 Feb 03
TA  - Neurology
PG  - 490--495
VI  - 84
IP  - 5
4099  - http://n.neurology.org/content/84/5/490.short
4100  - http://n.neurology.org/content/84/5/490.full
SO  - Neurology2015 Feb 03; 84
AB  - 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 31P 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 31P 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 31P 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.ANOVA=analysis of variance; ATP=adenosine triphosphate; BCAA=branched-chain amino acid; CoA=coenzyme A; fMRS=functional magnetic resonance spectroscopy; HD=Huntington disease; MRS=magnetic resonance spectroscopy; PCr=phosphocreatine; Pi=inorganic phosphate; UHDRS=Unified Huntington's Disease Rating Scale