RT001
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RT001
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 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. 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 mitocho ...
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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 lipid bilayer of the cell and organelle membranes contain polyunsaturated fatty acids (PUFA) are key components of cell and organelle membranes. Any process that either increases oxidation of PUFAs or hinders their ability to be replaced can lead to serious disease. Correspondingly, use of reinforced lipids that stop the chain reaction of lipid peroxidation has preventive and therapeutic potential. Examples of reinforced lipids There is a number of polyunsaturated fatty acids that can be reinforced by deuterisation. They include (the names of the reinforces deuterised versions are separated by a slash): * linoleic acid / D2-linoleic acid (D2-Lin) * α-linolenic acid / D4-α-linolenic acid (D4-Lnn) * arachidonic acid / D6-arachidonic acid (D6-A ...
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Retrotope
Retrotope, Inc. is a drug development company advancing the idea that polyunsaturated fatty acids (PUFA) drugs fortified with heavy isotopes (reinforced lipids) protect living cells by making bonds within the delicate molecules inside and around cells harder to break. This makes the cells less prone to damage caused by reactive oxygen species (ROS), one of the principal causes of ageing and age-associated diseases. Founded in 2006 by entrepreneurs and scientists with seed funding from private investors, Retrotope is developing a non-antioxidant approach to preventing lipid peroxidation, a detrimental factor in mitochondrial, neuronal, and retinal diseases. The company employs the virtual business model and works in scientific collaboration with more than 80 research groups in universities worldwide. Development Retrotope's drug platform, deuterium-stabilized polyunsaturated fatty acids (PUFA), prevents lipid peroxidation damage from propagating, rapidly stopping the toxic chain ...
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Isotope Effect On Lipid Peroxidation
Kinetic isotope effect, Isotope effect is observed when molecules containing heavier isotopes of the same atoms (for example, deuterium instead of hydrogen) are engaged in a chemical reaction at a slower rate. Reinforced lipids, Deuterium-reinforced lipids can be used for the protection of Cell (biology), living cells by slowing the chain reaction of lipid peroxidation. The lipid bilayer of the Cell (biology), cell and organelle membranes contain polyunsaturated fatty acids (PUFA) are key components of cell and organelle membranes. Any process that either increases oxidation of PUFAs or hinders their ability to be replaced can lead to serious disease. Correspondingly, drugs that stop the chain reaction of lipid peroxidation have preventive and therapeutic potential. Mechanism of isotope effect in general The mass of the atoms forming a chemical bond affects the bond’s strength. When two different isotopes of the same element exist, the heavier ones form stronger bonds. Stronger ...
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Deuterated Drug
A deuterated drug is a small molecule medicinal product in which one or more of the hydrogen atoms contained in the drug molecule have been replaced by its heavier stable isotope deuterium. Because of the kinetic isotope effect, deuterium-containing drugs may have significantly lower rates of metabolism, and hence a longer half-life. Mode of action Hydrogen is a chemical element with an atomic number of 1. It has just one proton and one electron. Deuterium is the heavier naturally occurring, non-radioactive, stable isotope of hydrogen. Deuterium was discovered by Harold Urey in 1931, for which he received the Nobel Prize in 1934. The deuterium isotope effect has become an important tool in the elucidation the mechanism of chemical reactions. Deuterium contains one proton, one electron, and a neutron, effectively doubling the mass of the deuterium isotope without changing its properties significantly. However, the C–D bond is a bit shorter, and it has reduced electronic polarizabi ...
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Orphan Drug
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy in many countries and has yielded medical breakthroughs that might not otherwise have been achieved, due to the economics of drug research and development. In the U.S. and the EU, it is easier to gain marketing approval for an orphan drug. There may be other financial incentives, such as an extended period of exclusivity, during which the producer has sole rights to market the drug. All are intended to encourage development of drugs which would otherwise lack sufficient profit motive to attract corporate research budgets and personnel. Definition According to the US Food and Drug Administration (FDA), an orphan drug is defined as one "intended for ...
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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 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills. Cause This condition is inherited in an autosomal recessive pattern, which means two copies of the gene (''PLA2G6'') in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder. Pathophysiology Mutations in the ''PLA2G6'' gene have been identified in most individuals with infantile neuroaxonal dystrophy. The ''PLA2G6'' gene provides instructions for making an enzyme called an A2 phospholipase. This enzyme family is involved i ...
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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 years of age. Many develop hypertrophic cardiomyopathy and require a mobility aid such as a cane, walker, or wheelchair in their teens. As the disease progresses, some affected people lose their sight and hearing. Other complications may include scoliosis and diabetes mellitus. The condition is caused by mutations in the ''FXN'' gene on chromosome 9, which makes a protein called frataxin. In FRDA, cells produce less frataxin. Degeneration of nerve tissue in the spinal cord causes the ataxia; particularly affected are the sensory neurons essential for directing muscle movement of the arms and legs through connections with the cerebellum. The spinal cord becomes thinner, and nerve cells lose some myelin sheath. No effective treatment is kn ...
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Lipid Peroxidation
Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which radical (chemistry), free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction#Chemical chain reactions, chain reaction mechanism. It most often affects polyunsaturated fatty acids, because they contain multiple double bonds in between which lie methylene bridges (-CH2-) that possess especially reactive hydrogen atoms. As with any radical reaction, the reaction consists of three major steps: initiation, propagation, and termination. The chemical products of this oxidation are known as lipid peroxides or lipid oxidation products (LOPs). Initiation Initiation is the step in which a fatty acid radical (chemistry), radical is produced. The most notable initiators in living cells are reactive oxygen species (ROS), such as hydroxyl radical, OH· and hydroperoxyl, HOO·, which combines wi ...
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Linoleic Acid
Linoleic acid (LA) is an organic compound with the formula COOH(CH2)7CH=CHCH2CH=CH(CH2)4CH3. Both alkene groups are cis-trans isomerism, ''cis''. It is a fatty acid sometimes denoted 18:2 (n-6) or 18:2 ''cis''-9,12. A linoleate is a salt (chemistry), salt or ester of this acid. Linoleic acid is a polyunsaturated fatty acid, polyunsaturated omega-6 fatty acid. It is a colorless liquid that is virtually insoluble in water but soluble in many organic solvents. It typically occurs in nature as a triglyceride (ester of glycerol, glycerin) rather than as a free fatty acid. It is one of two essential fatty acids for humans, who must obtain it through their diet, and the most essential, because the body uses it as a base to make the others. The word "linoleic" derives from the Latin ''linum'' "flax" + ''oleum'' "oil", reflecting the fact that it was first isolated from linseed oil. History In 1844, F. Sacc, working at the laboratory of Justus von Liebig, isolated linoleic acid from l ...
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Ethyl Esters
Ethyl may refer to: Arts and entertainment * Cold Ethyl, a Swedish rock band *Ethyl Sinclair, a character in the ''Dinosaurs'' television show Science and technology * Ethyl group, an organic chemistry moiety * Ethyl alcohol (or ethanol) * Ethyl Corporation, a fuel additive company ** Tetraethyllead Tetraethyllead (commonly styled tetraethyl lead), abbreviated TEL, is an organolead compound with the formula Pb( C2H5)4. It is a fuel additive, first being mixed with gasoline beginning in the 1920s as a patented octane rating booster that al ...-treated gasoline See also * Ethel (other) {{disambiguation ...
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Biochemistry
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and metabolism. Over the last decades of the 20th century, biochemistry has become successful at explaining living processes through these three disciplines. Almost all areas of the life sciences are being uncovered and developed through biochemical methodology and research. Voet (2005), p. 3. Biochemistry focuses on understanding the chemical basis which allows biological molecules to give rise to the processes that occur within living cells and between cells,Karp (2009), p. 2. in turn relating greatly to the understanding of tissues and organs, as well as organism structure and function.Miller (2012). p. 62. Biochemistry is closely related to molecular biology, which is the study of the molecular mechanisms of biological phenomena.As ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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