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) 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 ...

(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

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. 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 consti ...

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 re ...

, 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 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 (PU ...

that was taken into the clinic. It has passed Phase I/II clinical trial for the treatment of Friedreich's ataxia (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 granted RT001

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 o ...

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 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 Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

(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 (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