Achi news desk-
Researchers at Toron Universityi have found a way to better control the preclinical generation of depleted key neurons in Parkinson’s disease, pointing to a new approach to treating a disease with no cure and few effective treatments.
The researchers used an antibody to activate a receptor in a molecular signaling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter essential to brain health.
Researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons, to replace those lost in patients living with Parkinson’s disease. But efforts have been hampered in part by an inability to target specific receptors and areas of the brain.
“We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway,” he said. Stéphane Angersprincipal investigator on the study and director of the Donnelly Center for Cellular and Molecular Biology.
“We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway,” said Angers, who is also a professor at the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicineand holds the Charles H. Best Chair in Medical Research at U of T. “This method of activation has not been explored before.”
The study was recent published in the journal Development.
Parkinson’s disease is the second most common neurological disorder after Alzheimer’s disease, affecting over 100,000 Canadians. It particularly affects older men, increasingly impairing movement and causing pain as well as sleep and mental health problems.
Most previous research efforts to activate the Wnt signaling pathway have relied on the GSK3 enzyme inhibitor. This approach involves multiple signaling pathways for stem cell proliferation and differentiation, which can lead to unintended effects on the newly generated neurons and activation of off-target cells.
“We developed an efficient method for stimulating the differentiation of stem cells to produce neural cells in the midbrain,”He said Andy Which, first author of the study and a PhD student at the Donnelly Center. “Furthermore, cells activated through the FZD5 receptor closely resemble dopaminergic neurons of natural origin. “
Another promising finding of the study was that implanting the artificially produced neurons in a rodent model with Parkinson’s disease led to an improvement in the rodents’ locomotor impairment.
“Our next step would be to continue using rodent models or other suitable models to compare the results of activating the FZD5 receptor and inhibiting GSK3,” Yang said. “These experiments will confirm which method is more effective in improving the symptoms of Parkinson’s disease before clinical trials.”
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