Triheptanoin for the treatment of brain energy deficit: A 14-year experience

Fanny Mochel (1)

1 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute

Triheptanoin is an odd-chain triglyceride with anaplerotic properties—that is, replenishing the pool of metabolic intermediates in the Krebs cycle. Unlike even-chain fatty acids metabolized to acetyl-CoA only, triheptanoin can indeed provide both acetyl-CoA and propionyl-CoA, two key carbon sources for the Krebs cycle. Triheptanoin was initially used in patients with long-chain fatty acid oxidation disorders. The first demonstration of the possible benefit of triheptanoin for brain energy deficit came from a patient with pyruvate carboxylase deficiency, a severe metabolic disease that affects anaplerosis in the brain. In an open-label study, triheptanoin was then shown to decrease nonepileptic paroxysmal manifestations by 90% in patients with glucose transporter 1 deficiency syndrome, a disease that affects glucose transport into the brain. 31 P magnetic resonance spectroscopy studies also indicated that triheptanoin was able to correct bioen-ergetics in the brain of patients with Huntington disease, a neurodegenerative disease associated with brain energy deficit. Altogether, these studies indicate that tri-heptanoin can be a treatment for brain energy deficit related to altered anaplerosis and/or glucose metabolism .

Mots clés: Krebs cycle; astrocytes; GLUT1; Huntington disease; magnetic resonance spectroscopy

Domaines: Neurosciences [q-bio.NC]

Fanny Mochel. Triheptanoin for the treatment of brain energy deficit: A 14-year experience. Journal of Neuroscience Research, 2017, 95 (11), pp.2236 - 2243. ⟨10.1002/jnr.24111⟩. ⟨hal-01840222⟩