Treatment with triheptanoin, also known as C7, could be effective in very long-chain acyl-coenzyme A (CoA) dehydrogenase (VLCAD) deficiency, a type of long-chain fatty acid oxidation disorder (LCFAOD), according to results presented at the 2022 lecture series of the International Network for Fatty Acid Oxidation Research and Management (INFORM).
The current therapeutic options for VLCAD deficiency are limited and include the avoidance of fasting and limitation of exercise, a low-fat, high carbohydrate diet with frequent feeding, special nutritional treatment with medium-chain triglyceride oil supplementation, and treatment with triheptanoin, sold under the brand name Dojolvi®.
Here, Xue-Jun Zhao, MD, of Children’s Hospital of Pittsburgh in Pennsylvania wanted to compare the efficacy of a diet supplemented with triheptanoin vs IMB-203, a succinate prodrug currently in preclinical development.
To do so, he used a VLCAD knock-out mouse and fed the animals with either a triheptanoin chow diet or regular diet for 7 days or treated the animals with oral IMB-203 at a dose of 0.5mg/g twice a day for 7 days.
Read more about triheptanoin for the treatment of LCFAOD.
The results showed that both the animals fed with triheptanoin and those treated with IMB-203 had increased cold tolerance.
Moreover, treatment with a triheptanoin chow diet or triheptanoin oil reduced hepatic steatosis in the animals, whereas treatment with IMB-203 for 7 days had little effect.
The triheptanoin chow diet also reduced plasma levels of long-chain acylcarnitine. However, IMB-203 had no effect on the accumulation of acylcarnitine in the plasma of the animals.
“This study supports the use of C7 as an anaplerotic treatment for VLCAD deficiency and likely other long-chain fatty acid oxidation disorders,” Dr. Zhao concluded.
More research is needed to understand the potential of IMB-203 in improving energy production in diseases caused by inborn errors of metabolism such as LCFAODs.
Zhao XJ. Comparison of triheptanoin and succinate as anaplerotic treatment in a very long-chain acyl-CoA dehydrogenase deficiency mouse model. Lecture presented as part of International Network for Fatty Acid Oxidation Research and Management (INFORM) 2022 lecture series: May 23, 2022; Virtual.