Retrotope and collaborators led by Dr. Marie-Francoise Chesselet, the Charles H. Markham Professor of Neurology, and Interim Chair of the Department of Neurology at UCLA, have published a paper demonstrating that the Company’s D-PUFA drug candidate, RT001, reduces cognition deficits in a preclinical in vivo model of Huntington’s disease, while simultaneously downregulating brain lipid peroxidation biomarkers. The paper, entitled “Deuterium‐reinforced linoleic acid lowers lipid peroxidation and mitigates cognitive impairment in the Q140 knock in mouse model of Huntington’s disease,” was published in The FEBS Journal. A copy of the abstract may be found on The FEBS Journal website: https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.14590. This work was funded in part by a Fox Family Foundation grant to the Hereditary Disease Foundation (HDF), a non-profit research foundation which funds innovative genetic research towards curing Huntington’s disease and other brain disorders.
The study’s results demonstrate that Retrotope’s deuterated polyunsaturated linoleic acid drug candidate, RT001, rescues Q140 knock out mice from cognition deficits, while simultaneously downregulating brain lipid peroxidation markers. These data, together with prior publications of clinical and preclinical results, support the notion that mitigating lipid peroxidation using Retrotope’s deuterated polyunsaturated fatty acid (D-PUFA) drugs can be a disease-modifying therapy for multiple intractable neurodegenerative diseases.
Dr. Mikhail Shchepinov, CSO and co-founder of Retrotope, commented: “Lipid peroxidation has been implicated in many neurodegenerative diseases for decades, but has never been successfully addressed therapeutically. It is now evident from improvements noted in this Huntington’s model, a placebo-controlled Phase 1/2 disease clinical trial in Friedreich’s ataxia, continuing improvement in two Expanded Access subjects with the strictly progressive, fatal disease, Infantile Neuroaxonal Dystrophy, and dozens of specific animal and cell models of diseases, that lipid peroxidation is a validated, druggable target across many diseases of neurodegeneration.”
Dr. Robert Molinari, CEO of Retrotope adds: “This Huntington’s disease model now adds to multiple models of major and rare neurodegenerative diseases in which disease-modifying effects have been observed using D-PUFA drug candidates, including improvements in cognition and motor skills. Also, due to the essential role of PUFAs in membrane lipid remodeling essential for healthy cells, D-PUFAs are everywhere accessible to tissues that need them—an otherwise key obstacle in neurodegeneration. It’s time for the neurology community to embrace this new target class and drug strategies that effectively address it.”