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Potential treatment for Parkinson’s disease, YTX-7739, helps motor skills in mice

A basic investigational therapy by Yumanity Therapeutics, called YTX-7739, was found to improve motor skills and reduce clumping of toxic proteins in a mouse model of Parkinson’s disease (PD), the company said in a press release.

Data from this preclinical proof of concept study, titled “YTX-7739, a clinical stage stearoyl-CoA desaturase inhibitor for Parkinson’s disease, improves behavioral and pathological characteristics of an α-Synuclein mouse model,Is presented this week at the 5th Annual International Virtual Conference on Alzheimer’s and Parkinson’s Diseases (AD / PD 2021).

YTX-7739 is a small molecule designed to inhibit the activity of stearoyl-CoA desaturase (SCD), an enzyme involved in lipid metabolism and playing a role in the toxic accumulation of alpha-synuclein protein, characteristic of Parkinson’s disease and other neurodegenerative diseases.

As a small molecule, YTX-7739 can cross the blood-brain barrier, a selective semipermeable membrane that protects the brain from viruses and other insults that may be carried by the circulating blood.

The treatment has been reported to be safe and well tolerated in a Phase 1 clinical trial in healthy adults. A Phase 1b trial, also underway in the Netherlands, is currently evaluating the safety and efficacy of YTX-7739 in people with Parkinson’s disease, Yumanity reported. The first data should be released by the middle of the year.

“Inhibition of SCD … has been shown to prevent [alpha]-synuclein pathology in several models, including patient-derived neurons, ”said Dan Tardiff, PhD, acting head of research and scientific co-founder of Yumanity.

“The results of the current study demonstrate that YTX-7739 has a similar effect in a mouse model of Parkinson’s disease-related pathology,” added Tardiff, who presents the data at AD / PD 2021.

The mouse study, conducted in collaboration with researchers at Brigham & Women’s Hospital, evaluated the effectiveness of oral YTX-7739 in reducing motor defects, improving neuron survival, and attenuating other features of the disease. disease in a mouse model of Parkinson’s disease.

YTX-7739 was administered to Parkinson’s model mice and healthy mice, serving as a control group, from the age of 2 months through the age of 6 months.

Control mice and mice with Parkinson’s disease showed an 80% decrease in the fatty acid desaturation index in the brain, which measures SCD activity. This decrease in SCD activity was associated with improved motor function after four months of treatment with YTX-7739, as shown by the performance of the mice in pole climbing and rotating rod tests.

Brain levels of YTX-7739 were high enough to block SCD activity, resulting in lower levels of potentially disease-linked monounsaturated fatty acids in the blood and brain.

Alpha-synuclein levels were significantly reduced in mice treated with YTX-7739 compared to untreated animals. Treatment with YTX-7739 also improved the survival of dopaminergic neurons which are selectively lost in patients with Parkinson’s disease.

The advantages of The YTX-7739 treatment observed in this mouse model was also observed in neurons derived from the patient.

“These data highlight the essential role of lipid biology, particularly saturated fatty acids, in mediating the pathobiology of alpha-synuclein and support ongoing clinical evaluation. YTX-7739 as a disease-modifying drug for synucleinopathies, ”the researchers wrote.

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