Regulatory news: Dojolvi (triheptanoin) as a source of calories and fatty acids in long‐chain fatty acid oxidation disorders: FDA approval summary

Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

“…Despite being monogenetic diseases, we have previously shown that functional impairment of one enzyme or enzyme complex of the mitochondrial β-oxidation with the subsequent accumulation of acyl-residues results in a systemic alteration of complex lipids that possibly also contribute to the chronic neuropathic phenotype seen in LCHADD [ 19 ]. In this work we show that even and odd medium-chain fatty acids (mc-FAs) such as C7 and C8, which are commonly applied in the treatment of lc-FAOD [ 3 , 4 , 5 , 32 ], do not only represent a source of energy but also induce disease- and treatment-specific alteration in the lipidomic and proteomic profile when they are supplemented to LCHADD and VLCADD fibroblasts.…”

“…Therefore, treatment recommendations point at preventing catabolism and include avoidance of fasting, a fat-restricted diet and the application of medium-chain fatty acid (MCT oil) [ 3 , 4 ]. Recently, also the use of triheptanoin, a triglyceride with three molecules of heptanoic acid, was approved by the FDA for the treatment of lc-FAODs [ 5 ]. Both compounds contain either even or odd medium-chain fatty acids (mc-FAs) which are able to bypass the bottleneck represented by defective enzymes degrading lc-FA and can be fully metabolized, supplying organs and tissues with the required energy [ 6 , 7 ].…”

Prodrugs as empowering tools in drug discovery and development: recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates

“…This deficiency prevents the conversion of long-chain fatty acids into energy. 317 In long-chain fatty acid oxidation disorders, 8a is used as a source of medium chain fatty acids for patients. Unlike long-chain fatty acids, 8a is capable of traversing the double mitochondrial membrane without active transport by carnitine-based carrier.…”

Heptanoate Improves Compensatory Mechanism of Glucose Homeostasis in Mitochondrial Long-Chain Fatty Acid Oxidation Defect

“…Treatment recommendations include avoidance of prolonged fasting, restriction of long-chain fats in the diet, and supplementation with medium-chain triglycerides (MCTs) [8,9]. Recently, the FDA approved the additional use of triheptanoin for the treatment of long-chain fatty acid oxidation (lc-FAO) disorders [10]. Triheptanoin is a triglyceride composed of three heptanoates (C7-acyl groups) esterified to a glycerol backbone.…”