Di-deuterated linoleic acid ethyl ester
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| Routes of administration | Oral |
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| Formula | C20H34D2O2 |
| Molar mass | 310.5148 g/mol |
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| Density | 0.88 g/cm3 |
| Boiling point | 173–177 °C (343–351 °F) |
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Di-deuterated ethyl linoleate (also known as RT001; Di-deuterated linoleic acid ethyl ester, 11,11-D2-Ethyl Linoleate, Ethyl 11,11-D2-Linoleate)[1] 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.
Clinical development
Investigations of 11,11-D2-Ethyl linoleate (RT001) are being conducted in several neurological indications, including Friedreich’s ataxia and Infantile Neuroaxonal Dystrophy. A double-blind comparator-controlled Phase I/II clinical trial sponsored by Retrotope and Friedreich’s Ataxia Research Alliance was conducted to determine the safety profile and appropriate dosing for consequent trials.[2] 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.[3] In 2018 RT001 was given to a patient with ALS under a "compassionate use scheme".[4]
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.[5]