Compendium of the most significant studies with reference to properties, intake, effects.

Shirley M. Triheptanoin: First Approval. Drugs. 2020 Oct;80(15):1595-1600. doi: 10.1007/s40265-020-01399-5. Erratum in: Drugs. 2020 Nov;80(17):1873.

Abstract. This article summarizes the milestones in the development of triheptanoin leading to this first regulatory approval for use in the treatment of pediatric and adult patients with LC-FAOD.

Wehbe Z, Tucci S. Therapeutic potential of triheptanoin in metabolic and neurodegenerative diseases. J Inherit Metab Dis. 2020 May;43(3):385-391. doi: 10.1002/jimd.12199. 

Abstract. The present review summarises the published literature on the metabolism of triheptanoin including clinical reports related to the use of triheptanoin.

Vockley J, Burton B, Berry G, Longo N, Phillips J, Sanchez-Valle A, Chapman K, Tanpaiboon P, Grunewald S, Murphy E, Lu X, Cataldo J. Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation disorders: Results from an open-label, long-term extension study. J Inherit Metab Dis. 2021 Jan;44(1):253-263. doi: 10.1002/jimd.12313.

Abstract. Long-chain fatty acid oxidation disorders (LC-FAOD) are autosomal recessive conditions that impair conversion of long-chain fatty acids into energy, leading to significant clinical symptoms. 

Laemmle A, Steck AL, Schaller A, Kurth S, Perret Hoigné E, Felser AD, Slavova N, Salvisberg C, Atencio M, Mochel F, Nuoffer JM, Gautschi M. Triheptanoin - Novel therapeutic approach for the ultra-rare disease mitochondrial malate dehydrogenase deficiency. Mol Genet Metab Rep. 2021 Oct 19;29:100814. doi: 10.1016/j.ymgmr.2021.100814.

Abstract. Mitochondrial malate dehydrogenase (MDH2) deficiency (MDH2D) is an ultra-rare disease with only three patients described in literature to date. MDH2D leads to an interruption of the tricarboxylic acid (TCA) cycle and malate-aspartate shuttle (MAS) and results in severe early onset encephalopathy.

Norris MK, Scott AI, Sullivan S, Chang IJ, Lam C, Sun A, Hahn S, Thies JM, Gunnarson M, McKean KN, Merritt JL 2nd. Tutorial: Triheptanoin and Nutrition Management for Treatment of Long-Chain Fatty Acid Oxidation Disorders. JPEN J Parenter Enteral Nutr. 2021 Feb;45(2):230-238. doi: 10.1002/jpen.2034. 

Abstract. We report the complex medical and nutrition management of triheptanoin therapy initiated emergently for 3 patients with long-chain fatty acid oxidation disorders.

Lee SK, Gupta M, Shi J, McKeever K. The Pharmacokinetics of Triheptanoin and Its Metabolites in Healthy Subjects and Patients With Long-Chain Fatty Acid Oxidation Disorders. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1325-1334. doi: 10.1002/cpdd.944.

Abstract. The pharmacokinetics of triheptanoin and circulating metabolites were explored in healthy subjects and patients with LC-FAODs using noncompartmental analyses. 

Vockley J, Longo N, Madden M, Dwyer L, Mu Y, Chen CY, Cataldo J. Dietary management and major clinical events in patients with long-chain fatty acid oxidation disorders enrolled in a phase 2 triheptanoin study. Clin Nutr ESPEN. 2021 Feb;41:293-298. doi: 10.1016/j.clnesp.2020.11.018.

Abstract. Long-chain fatty acid oxidation disorders (LC-FAOD) are rare, life-threatening, autosomal recessive disorders that lead to energy depletion and major clinical events (MCEs), such as acute metabolic crises of hypoglycemia, cardiomyopathy, and rhabdomyolysis. The aim of this study was to report a post hoc analysis of diet diary data from the phase 2 UX007-CL201 study

Vockley J, Burton B, Berry G, Longo N, Phillips J, Sanchez-Valle A, Chapman K, Tanpaiboon P, Grunewald S, Murphy E, Lu X, Cataldo J. Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation disorders: Results from an open-label, long-term extension study. J Inherit Metab Dis. 2021 Jan;44(1):253-263. doi: 10.1002/jimd.12313.

Abstract. Long-chain fatty acid oxidation disorders (LC-FAOD) are autosomal recessive conditions that impair conversion of long-chain fatty acids into energy, leading to significant clinical symptoms. 

McDonald T, Hodson MP, Bederman I, Puchowicz M, Borges K. Triheptanoin alters [U-13C6]-glucose incorporation into glycolytic intermediates and increases TCA cycling by normalizing the activities of pyruvate dehydrogenase and oxoglutarate dehydrogenase in a chronic epilepsy mouse model. J Cereb Blood Flow Metab. 2020 Mar;40(3):678-691. doi: 10.1177/0271678X19837380.

Abstract. Here, we investigated changes in glucose metabolism by triheptanoin interictally in the chronic stage of the pilocarpine mouse epilepsy model.

Yuan X, Wang L, Tandon N, Sun H, Tian J, Du H, Pascual JM, Guo L. Triheptanoin Mitigates Brain ATP Depletion and Mitochondrial Dysfunction in a Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2020;78(1):425-437. doi: 10.3233/JAD-200594.

Abstract. Brain energy failure is an early pathological event associated with synaptic dysfunction in Alzheimer's disease (AD). Thus, mitigation or enhancement of brain energy metabolism may offer a therapeutic avenue. However, there is uncertainty as to what metabolic process(es) may be more appropriate to support or augment since metabolism is a multiform process such that each of the various metabolic precursors available is utilized via a specific metabolic pathway. In the brain, these pathways sustain not only a robust rate of energy production but also of carbon replenishment.

Engelstad K, Salazar R, Koenigsberger D, Stackowtiz E, Brodlie S, Brandabur M, De Vivo DC. Exploring triheptanoin as treatment for short chain enoyl CoA hydratase deficiency. Ann Clin Transl Neurol. 2021 May;8(5):1151-1157. doi: 10.1002/acn3.51359.

Abstract. We explored the benefits of triheptanoin as a treatment for Short Chain Enoyl Co-A Hydratase (SCEH) deficiency.