Treatment with triheptanoin could decrease disease manifestations in critically ill patients with long chain fatty acid oxidation disorders (LCFAODs), a new study published in Molecular Genetics found.
The participants of this study were patients who remained in critical care units at specialized centers despite having received standard treatment. Once on triheptanoin administration, most of them survived the trigger event, and 73% improved LCFAOD-associated parameters such as left ventricular ejection fraction and left ventricular mass.
Also, of all patients who required either ventilation/extracorporeal membrane oxygenation, cardiopulmonary resuscitation, mechanical intervention, and vasopressors, 64% improved to such an extent that they stopped requiring such supportive measures.
These promising findings regarding cardiac function were specially marked in infants with cardiomyopathies. “Early treatment with triheptanoin rather than even chain medium-chain triglycerides oil and/or nutritional management alone may prevent life-threatening major clinical events, which may reduce mortality,” the authors wrote.
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Triheptanoin, a synthetic medium odd-chain triglyceride with 3, 7-carbon fatty acids on a glycerol backbone, has shown its digestion produces no symptoms in patients with LCFAOD and has, until recently, only been approved for clinical trials. In this article, most of the users tolerated the drug well without experiencing important adverse effects. No deaths could be attributed to the medication but rather to the underlying disease. Finally, 85% of the participants continued treatment with triheptanoin after discharge, and 67% still adhered to the therapeutic scheme by the final follow-up.
This retrospective study conducted by Vockley and his team included 67 individuals previously diagnosed with LCFAODs who received triheptanoin and whose physicians completed the data questionnaires. Among all, isolated 3-hydroxyacyl-CoA dehydrogenase deficiency was the most common diagnosis accounting for 35%, followed by very long-chain acyl-coenzyme A dehydrogenase, carnitine palmitoyltransferase 2, carnitine-acylcarnitine translocase and trifunctional protein deficiencies in 29%, 14%, 12% and 8% of the cases, respectively.
“The totality of the data presented herein are consistent with the existing positive benefit/risk profile of triheptanoin, and the value of treatment with triheptanoin in patients with [LCFAOD] with acute life threatening [major clinical events] in critical care and emergency settings,” the authors concluded.
“The improvements observed in cardiomyopathy, particularly in infants, highlight the potential of triheptanoin to improve mortality outcomes in these high-risk populations and suggest that pre-symptomatic therapy might further reduce morbidity and mortality.”
Vockley J, Enns G, Ramirez A, et al. Response to triheptanoin therapy in critically ill patients with LC-FAOD: report of patients treated through an expanded access program. Mol Genet Metab. Published online April 11, 2022. doi:10.1016/j.ymgme.2022.04.001