Dr. Suneil Kalia,
Assistant Professor, University of Toronto;
Scientist, Toronto Western Research Institute
Pilot Project Grant: $45,000
Inhibition of BAG5 to mitigate alpha-synuclein
oligomerization and neurodegeneration in Parkinson’s disease
One of the most difficult aspects of Dr. Suneil Kalia’s practice as a neurosurgeon is the moment he has to tell patients treated for years at Toronto Western’s Movement Disorders Clinic that neurologists no longer have anything to offer them that will significantly relieve their symptoms of Parkinson’s disease.
“Our therapies only target certain areas of the disease, but do not target the disease as a whole,” says Kalia, a neurosurgeon at Toronto Western Hospital. “At some point, we become limited in our ability to help our patients.”
The frustration of seeing dopamine-replacement medication and even the surgical techniques of deep brain stimulation stop working as Parkinson’s progresses drove Kalia into a different direction to help people living with this degenerative disease. Already both a neurosurgeon and a molecular biologist, Kalia also became a neuroscientist. He began studying the causes of Parkinson’s disease – and in particular the proteins involved in the death of dopamine-producing brain cells.
Kalia is focused on so-called “chaperone” proteins. These proteins can accompany another protein called alpha-synuclein. Misfolded or misshaped clumps of alpha-synuclein can accumulate in dopamine-producing brain cells and cause them to die. Since these brain cells are critical to controlling movement, their death causes Parkinson’s disease.
Identifying the role of these chaperone proteins and their relationship to alpha-synuclein would go a long way to solving the puzzle of why the dopamine neurons die, Kalia believes. He thinks “bad” or malfunctioning chaperone proteins cause the alpha-synuclein to clump up in the brain cells. Knocking down these bad chaperone proteins might stop the aberrant process.
Using a type of gene therapy that delivers a virus to dopamine-producing neurons, Kalia hopes to eliminate the bad chaperone proteins and save the brain cells that are so critically involved in the motor symptoms of Parkinson’s disease.
“If we inhibit these molecules, we have the potential of stopping or reversing the degenerative process, and… this could be a novel class of therapies for the disease,” Kalia says.
The resilience of his patients inspires Kalia, who hopes his research will eventually lead to a single treatment that will significantly improve the lives of people living with Parkinson’s disease.