Mattia Volta,
Post-Doctoral Fellow, University of British Columbia
Basic Research Fellowship: $100,000 over two years

The role of LRRK2 in the development and transmission of acute alpha-synuclein neuropathology

Although researchers haven’t pinpointed what triggers most forms of Parkinson’s disease, the interaction or collaboration among multiple genes and proteins is almost certainly critical to the spread of the illness from one damaged brain cell to another.

At the University of British Columbia, neuroscientist Mattia Volta concentrates on the relationship between the proteins alpha-synuclein and LRRK2 – and what happens if you can take one of those proteins out of the equation. Volta, who began studying Parkinson’s disease in his native Italy, works with animal models missing the LRRK2 protein. He documents what happens when mice without LRRK2 are treated with a substance to replicate the alpha-synuclein protein. Clumps of alpha-synuclein are present in the brain cells of people with Parkinson’s disease, and mutated forms of both proteins cause familial forms of Parkinson’s. Volta has collected preliminary data indicating mice without LRRK2 are free from the cognitive impairment or memory loss that occurs in mice that have both LRRK2 and alpha-synuclein present in their brains.

“Removing LRRK2 appears to be protective when it’s early in the disease’s progression,” Volta says.

Now he’s investigating whether the absence of LRRK2 in mice also protects them against the motor problems and progression of the disease that follow cognitive changes and memory loss in Parkinson’s disease. Eventually, Volta will knock out LRRK2 to see if removing the first protein can reverse or stop the brain cell death that clumps of alpha-synuclein cause.

“Taking it out is quite a drastic approach,” says Volta. But researchers believe other proteins compensate when LRRK2 is removed. Removing LRRK2 might be enough to halt the interaction with alpha-synuclein that causes some forms of Parkinson’s disease.

Ultimately, Volta hopes his work will point the way toward a new treatment avenue or genetic therapy that can be tested in people. Volta, whose grandfather died of Alzheimer’s disease, has long been fascinated by how neurodegenerative diseases rob people of their personalities. He hopes one day to have his own lab exploring causes for several of these debilitating brain disorders, including Parkinson’s, Alzheimer’s, and Huntington’s disease.