[{"@context":"http:\/\/schema.org\/","@type":"BlogPosting","@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/di-deuterated-linoleic-acid-ethyl-ester\/#BlogPosting","mainEntityOfPage":"https:\/\/wiki.edu.vn\/en\/wiki40\/di-deuterated-linoleic-acid-ethyl-ester\/","headline":"Di-deuterated linoleic acid ethyl ester","name":"Di-deuterated linoleic acid ethyl ester","description":"From Wikipedia, the free encyclopedia Di-deuterated ethyl linoleate (also known as RT001, di-deuterated linoleic acid ethyl ester, 11,11-d2-ethyl linoleate, or","datePublished":"2016-04-27","dateModified":"2016-04-27","author":{"@type":"Person","@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/author\/lordneo\/#Person","name":"lordneo","url":"https:\/\/wiki.edu.vn\/en\/wiki40\/author\/lordneo\/","image":{"@type":"ImageObject","@id":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/c9645c498c9701c88b89b8537773dd7c?s=96&d=mm&r=g","height":96,"width":96}},"publisher":{"@type":"Organization","name":"Enzyklop\u00e4die","logo":{"@type":"ImageObject","@id":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","url":"https:\/\/wiki.edu.vn\/wiki4\/wp-content\/uploads\/2023\/08\/download.jpg","width":600,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?type=1x1","url":"https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?type=1x1","height":"1","width":"1"},"url":"https:\/\/wiki.edu.vn\/en\/wiki40\/di-deuterated-linoleic-acid-ethyl-ester\/","wordCount":3406,"articleBody":"From Wikipedia, the free encyclopediaDi-deuterated ethyl linoleate (also known as RT001, di-deuterated linoleic acid ethyl ester, 11,11-d2-ethyl linoleate, or ethyl 11,11-d2-linoleate)[1] is an experimental, orally-bioavailable synthetic deuterated polyunsaturated fatty acid (PUFA), a part of reinforced lipids.  It is an isotopologue of linoleic acid, an essential omega-6 PUFA. The deuterated compound, while identical to natural linoleic acid except for the presence of deuterium, is resistant to lipid peroxidation which makes studies of its cell-protective properties worthwhile.Table of ContentsMechanism of action[edit]Clinical development[edit]Friedreich’s ataxia[edit]Infantile neuroaxonal dystrophy[edit]Phospholipase 2G6-associated neurodegeneration[edit]Amyotrophic lateral sclerosis[edit]Progressive supranuclear palsy[edit]Preclinical research[edit]Alzheimer’s disease[edit]References[edit]Mechanism of action[edit]An animated illustration of a chain reaction with slow elementsDi-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 isotope effect \u2014 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.[2][3]Clinical development[edit]Friedreich’s ataxia[edit]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.[4] 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.[5] Another randomised, double-blind, placebo-controlled clinical study began in 2019.[6]Infantile neuroaxonal dystrophy[edit]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.[7]Phospholipase 2G6-associated neurodegeneration[edit]In 2017, the FDA granted RT001 orphan drug designation in the treatment of phospholipase 2G6-associated neurodegeneration (PLAN).[8]Amyotrophic lateral sclerosis[edit]In 2018, RT001 was given to a patient with amyotrophic lateral sclerosis (ALS) under a “compassionate use scheme”.[9]Progressive supranuclear palsy[edit]In 2020, the FDA granted orphan drug designation RT001 for the treatment of patients with progressive supranuclear palsy (PSP). PSP is a disease involving modification and dysfunction of tau protein; RT001\u2019s mechanism of action both lowers lipid peroxidation and prevents mitochondrial cell death of neurons which is associated with disease onset and progression.[10]Preclinical research[edit]Alzheimer’s disease[edit]RT001 has been shown to be effective in a model of Alzheimer’s disease in mice.[11]References[edit]^ “9-cis, 12-cis-11,11-D2-Linoleic acid ethyl ester”. PubChem.^ Hill S, Lamberson CR, Xu L, To R, Tsui HS, Shmanai VV,  et\u00a0al. (August 2012). “Small amounts of isotope-reinforced polyunsaturated fatty acids suppress lipid autoxidation”. Free Radical Biology & Medicine. 53 (4): 893\u2013906. doi:10.1016\/j.freeradbiomed.2012.06.004. PMC\u00a03437768. PMID\u00a022705367.^ Demidov VV (August 2020). “Site-specifically deuterated essential lipids as new drugs against neuronal, retinal and vascular degeneration”. Drug Discovery Today. 25 (8): 1469\u20131476. doi:10.1016\/j.drudis.2020.03.014. PMID\u00a032247036. S2CID\u00a0214794450.^ Clinical trial number NCT02445794 for “A First in Human Study of RT001 in Patients With Friedreich’s Ataxia” at ClinicalTrials.gov^ Zesiewicz T, Heerinckx F, De Jager R, Omidvar O, Kilpatrick M, Shaw J, Shchepinov MS (July 2018). “Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich’s ataxia”. Movement Disorders. 33 (6): 1000\u20131005. doi:10.1002\/mds.27353. PMID\u00a029624723. S2CID\u00a04664990.^ Clinical trial number NCT04102501 for “A Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Friedreich’s Ataxia” at ClinicalTrials.gov^ Clinical trial number NCT03570931 for “A Study to Assess Efficacy and Safety of RT001 in Subjects With Infantile Neuroaxonal Dystrophy” at ClinicalTrials.gov^ “US FDA Grants Orphan Drug Designation for Retrotope’s RT001 in the Treatment of Phospholipase 2G6 (PLA2G6)-Associated Neurodegeneration”. Global Newswire. 2 November 2017.^ Inacio P (2018-09-18). “Experimental RT001 Now Available for ALS Under Expanded Access”. ALS News Today.^ “RT001 Gets Orphan Drug Designation in Progressive Supranuclear Palsy”.^ Butterfield DA, Halliwell B (March 2019). “Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease”. Nature Reviews. Neuroscience. 20 (3): 148\u2013160. doi:10.1038\/s41583-019-0132-6. PMC\u00a09382875. PMID\u00a030737462. S2CID\u00a059617957."},{"@context":"http:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/#breadcrumbitem","name":"Enzyklop\u00e4die"}},{"@type":"ListItem","position":2,"item":{"@id":"https:\/\/wiki.edu.vn\/en\/wiki40\/di-deuterated-linoleic-acid-ethyl-ester\/#breadcrumbitem","name":"Di-deuterated linoleic acid ethyl ester"}}]}]