Di-deuterated linoleic acid ethyl ester
|Chemical and physical data|
|Molar mass||310.5148 g/mol g·mol−1|
|3D model (JSmol)|
|Boiling point||173–177 °C (343–351 °F)|
|(what is this?)|
Di-deuterated ethyl linoleate (also known as RT001; di-deuterated linoleic acid ethyl ester, 11,11-d2-ethyl linoleate, ethyl 11,11-d2-linoleate) is an experimental, orally-bioavailable synthetic deuterated polyunsaturated fatty acid (PUFA), an isotopologue of an essential omega-6 PUFA, linoleic acid. The deuterated compound, while identical to natural linoleic acid, is resistant to lipid peroxidation which makes studies of its cell-protective properties worthwhile.
Mechanism of action
Di-deuterated linoleic acid is recognized by cells as identical to the natural linoleic acid. But when taken up, it is converted into 13,13-D2-arachidonic acid, a heavy isotope version of arachidonic acid, that gets incorporated into lipid membranes. The deuterated compound resists the non-enzymatic lipid peroxidation (LPO) through a non-antioxidant based mechanism that protects mitochondrial, neuronal and other lipid membranes, thereby greatly reducing the levels of numerous LPO-derived toxic products such as reactive carbonyls.
A double-blind comparator-controlled Phase I/II clinical trial for Friedreich’s ataxia, sponsored by Retrotope and Friedreich’s Ataxia Research Alliance, was conducted to determine the safety profile and appropriate dosing for consequent trials. RT001 was promptly absorbed and was found to be safe and tolerable over 28 days at the maximal dose of 9 g/day. It improved peak workload and peak oxygen consumption in the test group compared to the control group who received the equal doses of normal, non-deuterated ethyl linoleate.
Infantile neuroaxonal dystrophy
An open-label clinical study for infantile neuroaxonal dystrophy evaluating long-term evaluation of efficacy, safety, tolerability, and pharmacokinetics of RT001, which, when taken with food, can protect the neuronal cells from degeneration, started in the Summer 2018.
Phospholipase 2G6-associated neurodegeneration
Amyotrophic lateral sclerosis
- "9-cis, 12-cis-11,11-D2-Linoleic acid ethyl ester".
- PMID 22705367
- Zesiewicz, Theresa; Heerinckx, Frederic; De Jager, Robert; Omidvar, Omid; Kilpatrick, Marcus; Shaw, Jessica; Shchepinov, Mikhail S. (2018). "Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich's ataxia". Movement Disorders. 33 (6): 1000–1005. doi:10.1002/mds.27353. PMID 29624723.
- "US FDA Grants Orphan Drug Designation for Retrotope's RT001 in the Treatment of Phospholipase 2G6 (PLA2G6)-Associated Neurodegeneration". Global Newswire. 2 November 2017.
- "Experimental RT001 Now Available for ALS Under Expanded Access". 2018-09-18.
- Butterfield, D. Allan; Halliwell, Barry (2019). "Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease". Nature Reviews Neuroscience. 20 (3): 148–160. doi:10.1038/s41583-019-0132-6. PMID 30737462.