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New Targets Found for Huntington’s, Parkinson’s

Wed, 01/08/2024 - 12:11pm
Western University of Ontario researchers have discovered a possible new target for treating movement disorders such as Huntington’s disease and Parkinson’s disease.
 
 
Schulich School of Medicine & Dentistry professor Stephen Ferguson, also a scientist at Western’s Robarts Research Institute, and Fabiola Ribeiro, of the Universidad Federal de Minas Gerais in Brazil, found improvement in motor behaviors in a Huntington’s disease mouse model when one of the major neurotransmitters in the brain, called Metabotropic Glutamate Receptor 5 (mGluR5), was deleted.
 
The research is published online in Human Molecular Genetics.
 
Huntington’s disease is an inherited neurodegenerative disorder which causes uncontrolled movement, and eventually cognitive decline and emotional disturbances.
 
Working in the Ferguson lab, where Ribeiro was a postdoctoral trainee, the scientists crossed two mouse models – one without glutamate receptors, one a Huntington’s mouse model which over-expresses mutant human Huntington’s protein. 
 
The researchers found if they deleted mGluR5, they lost the pathology of Huntington’s in the neurons, and saw improvements in motor behavior, normally impaired in these mice.
 
“What we found was, if we block mGluR5, which is the glutamate receptor we’re interested in, the mice become hyper-locomotive. They become able to move better than wild type mice suggesting glutamate receptors might be a good target for treating movement disorders such as Parkinson’s disease. That was a bit of a surprise, and we can show that genetically and pharmaceutically,” said Ferguson, who holds a Canada Research Chair in Molecular Neurobiology.
 
“The good thing is, there are mGluR5 antagonists now in stage three clinical trials (for diseases such as Fragile X)," Ferguson said. "So, it is quite possible these drugs will be available for patients in the future.”
 
The research was funded by the Canadian Institutes of Health Research.
 
 

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