Di-deuterated ethyl linoleate (also known as RT001, di-deuterated linoleic acid ethyl ester, 11,11-''d₂''-ethyl linoleate, or ethyl 11,11-''d₂''-linoleate) is an experimental, orally-bioavailable synthetic

deuterated Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...

polyunsaturated fatty acid Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...

(PUFA), a part of

reinforced lipids Reinforced lipids are lipid molecules in which some of the fatty acids contain deuterium instead of hydrogen. They can be used for the protection of living cells by slowing the chain reaction due to isotope effect on lipid peroxidation. The lipi ...

. It is an

isotopologue In chemistry, isotopologues are molecules that differ only in their isotopic composition. They have the same chemical formula and bonding arrangement of atoms, but at least one atom has a different number of neutrons than the parent. An exampl ...

linoleic acid Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid. ...

, an essential

omega-6 Omega-6 fatty acids (also referred to as ω-6 fatty acids or ''n''-6 fatty acids) are a family of polyunsaturated fatty acids that have in common a final carbon-carbon double bond in the ''n''-6 position, that is, the sixth bond, counting from ...

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.

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 isotope effect — 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.

Clinical development

Friedreich's ataxia

A double-blind comparator-controlled Phase I/II clinical trial for

Friedreich's ataxia Friedreich's ataxia (FRDA or FA) is an autosomal-recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time. Symptoms generally start between 5 and 20 year ...

, sponsored by Retrotope and

Friedreich's Ataxia Research Alliance The Friedreich's Ataxia Research Alliance (FARA) is a 501(c)(3), non-profit, tax-exempt organization formed to support the research on Friedreich's ataxia Friedreich's ataxia (FRDA or FA) is an autosomal-recessive genetic disease that c ...

, 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. Another randomised, double-blind, placebo-controlled clinical study began in 2019.

Infantile neuroaxonal dystrophy

An open-label clinical study for

infantile neuroaxonal dystrophy Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and ...

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

In 2017, the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

granted RT001 orphan drug designation in the treatment of phospholipase 2G6-associated neurodegeneration (

PLAN A plan is typically any diagram or list of steps with details of timing and resources, used to achieve an objective to do something. It is commonly understood as a temporal set of intended actions through which one expects to achieve a goal. ...

Amyotrophic lateral sclerosis

In 2018, RT001 was given to a patient with amyotrophic lateral sclerosis (ALS) under a "compassionate use scheme".

Progressive supranuclear palsy

In 2020, the FDA granted orphan drug designation RT001 for the treatment of patients with

progressive supranuclear palsy Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...

(PSP). PSP is a disease involving modification and dysfunction of tau protein; RT001’s mechanism of action both lowers lipid peroxidation and prevents mitochondrial cell death of neurons which is associated with disease onset and progression.