TY - JOUR
T1 - Triheptanoin improves brain energy metabolism in patients with Huntington disease
AU - Adanyeguh, Isaac Mawusi
AU - Rinaldi, Daisy
AU - Henry, Pierre Gilles
AU - Caillet, Samantha
AU - Valabregue, Romain
AU - Durr, Alexandra
AU - Mochel, Fanny
N1 - Publisher Copyright:
© 2015 American Academy of Neurology.
PY - 2015
Y1 - 2015
N2 - 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 proofof- 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 5 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 5 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.
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 proofof- 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 5 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 5 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.
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U2 - 10.1212/WNL.0000000000001214
DO - 10.1212/WNL.0000000000001214
M3 - Article
C2 - 25568297
AN - SCOPUS:84925959180
VL - 84
SP - 490
EP - 495
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 5
ER -