title: 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).
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  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.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Isaac Mawusi
authors.initials: IM
authors.lastname: Adanyeguh
authors.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Daisy
authors.initials: D
authors.lastname: Rinaldi
authors.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Henry
authors.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Samantha
authors.initials: S
authors.lastname: Caillet
authors.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabregue
authors.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: From Inserm U 1127 (I.M.A., D.R., R.V., A.D., F.M.), CNRS UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Center for Magnetic Resonance Research (P.-G.H.), University of Minnesota, Minneapolis; Departments of Dietetics (S.C.) and Genetics (A.D., F.M.), AP-HP, Pitié-Salpêtrière University Hospital, Paris; and Center for NeuroImaging Research (R.V.), Institut du Cerveau et de la Moelle épinière, Paris, France. fanny.mochel@upmc.fr.
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014280:Triglycerides; C531010:triheptanoin