Retrotope, Inc. is a drug development company advancing the idea that

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 ...

s (PUFA) drugs fortified with heavy isotopes (

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 ...

) 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 In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS), one of the principal causes of ageing and age-associated diseases. Founded in 2006 by entrepreneurs and scientists with

seed funding Seed money, sometimes known as seed funding or seed capital, is a form of securities offering in which an investor invests capital in a startup company in exchange for an equity stake or convertible note stake in the company. The term ''seed'' su ...

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 A virtual business model (not to be confused with Virtual business) is a way to organize a startup company. In the virtual company, the utilization of the financial resources can be optimized with cost-effective product development as a result. Th ...

and works in scientific collaboration with more than 80 research groups in universities worldwide.

Development

Retrotope's drug platform, deuterium-stabilized

s (PUFA), prevents lipid peroxidation damage from propagating, rapidly stopping the toxic chain reaction at its source. Because the fatty acids in mitochondrial and cellular membranes turn over rapidly, the dietary substitution of stabilized fatty acids creates cells fortified against damage due to

kinetic isotope effect In physical organic chemistry, a kinetic isotope effect (KIE) is the change in the reaction rate of a chemical reaction when one of the atoms in the reactants is replaced by one of its isotopes. Formally, it is the ratio of rate constants for th ...

. 11,11-D2-ethyl linoleate suppresses lipid peroxidation even at relatively low levels of incorporation into membranes. In 2010 Retrotope found that it more than 150 times increases the resistance of the

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

, later it was shown to be effective in an animal model of Alzheimer's disease. A June 2018 study found that a diet of D-PUFA was shown to significantly decrease F2-isoprostanes (a cerebrospinal fluid found in elevated amounts in Huntington's disease) when fed to one-month old mice over the course of five months. These findings caused discussion in popular science press about the use of deuterated nutrients against ageing, but the most promising direction of further development was toward rare

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

s in which oxidative damage plays a part.

Clinical trials

Friedreich's ataxia

The first deuterated PUFA made and studied by Retrotope, 11,11-D2-ethyl linoleate, has become the first Retrotope's drug RT001 that was taken into the clinic. It has passed Phase I/II clinical trial for the treatment of

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 ...

(FA), in which RT001 was shown to be safe, well tolerated and beneficial in terms of improving motor capability in FA patients. However, this preliminary evidence must be interpreted with caution given the limited sample size and the short duration of the study.

Phospholipase 2G6-associated neurodegeneration

In 2017

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. ...

Infantile neuroaxonal dystrophy

A Phase II open-label clinical study for long-term evaluation of efficacy, safety, tolerability, and pharmacokinetics of RT001 in the treatment of

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 ...

started in the Summer 2018.

Other clinical use

Amyotrophic lateral sclerosis

After a petition for access filed by investigators at major medical centers, in 2018 RT001 was given to a patient with amyotrophic lateral sclerosis (ALS) under a "compassionate use" scheme sponsored by Retrotope.

Progressive supranuclear palsy

In 2020 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.

References

{{Reflist Pharmaceutical companies of the United States