Mathers Foundation Grant Fuels Study of Parkinson’s-associated Genes

The G. Harold and Leila Y. Mathers Foundation has awarded a three-year grant to a team of researchers at the Massachusetts Institute of Technology’s  (MIT) Picower Institute for Learning and Memory to screen for genes that may be key for brain cells to resist Parkinson’s disease-associated neurodegeneration.

The grant, which began Jan. 1, was awarded to principal investigator Myriam Heiman, PhD, an associate professor in the department of brain and cognitive sciences and a core member of The Picower Institute and the Broad Institute of MIT and Harvard.

“I’m extremely grateful for this generous support and recognition of our work from the Mathers Foundation, and hope that our study will elucidate new therapeutic targets for the treatment and even prevention of Parkinson’s disease,” Heiman said in a press release.

Parkinson’s is characterized by a gradual loss of dopamine-producing neurons in the substantia nigra (a brain region that controls movement and balance),  leading to severe motor impairments. Dopamine is a chemical messenger (neurotransmitter) that allows communication between nerve cells (neurons).

However, what makes these cells more vulnerable to the disease’s damage remains largely unknown, as well as the molecular mechanisms that characterize neurodegeneration-resistant neurons.

“There is currently no molecular explanation for the brain cell loss seen in Parkinson’s disease or a cure for this devastating disease,” Heiman said.

To help fill this knowledge gap, Heiman and her team will search for genes that allow neurons to resist the cellular and molecular changes driven by Parkinson’s disease in mouse models of the disease.

Such genes will be identified through an innovative method that involves turning off, one by one, each of the 22,000 genes that are active in the mouse brain, in neurons from Parkinson’s mouse models and healthy mice.

This will allow researchers to determine which genes, when missing, contribute to neuronal death, and are therefore essential for neuron survival. The products of these genes then can be evaluated as potential therapeutic targets for Parkinson’s.

This technology was used previously by Heiman’s team to discover genes that promoted neuron survival in Huntington’s disease, another neurodegenerative disorder in which a specific population of dopamine-receiving neurons is particularly vulnerable.

With the new award, the team will use the method to study Parkinson’s disease.

“This award will allow us to perform unbiased, genome-wide genetic screens in the brains of mouse models of Parkinson’s disease, probing for genes that allow brain cells to survive the effects of cellular perturbations associated with Parkinson’s disease,” Heiman said.

The foundation awarded another three-year grant to a team of researchers at MIT’s McGovern Institute who will map changes in brain’s gene activity in response to addictive substances or medicines. Notably, dopamine also is involved in the processes that allow a person to learn which behaviors and contexts lead to reward, which are hijacked by addictive drugs.