Dr. John Woulfe
Ottawa Hospital Research Institute
Pilot project grant
$45,000 over 1 year

Alpha-synuclein in the vermiform appendix of Parkinson disease patients: A window on disease initiation.

Decades before Parkinson’s disease begins killing the brain cells that generate dopamine, the chemical that is critical for controlling movement, the illness has already begun its work in nerves stimulating the gut, researchers now believe.

At the University of Ottawa, Dr. John Woulfe, a neuropathologist, is investigating the role those nerves, which flow from the appendix to the brain, may play in the genesis of Parkinson’s disease.

Within brain cells, clumps of a protein called alpha-synuclein have already been implicated in Parkinson’s disease. If dopamine-producing brain cells cannot get rid of those protein clumps, they die.

Now, Woulfe and his colleagues have found those same clumps of alpha-synuclein in the walls of the appendix and the surrounding nerves. He has also found these clumps of the protein within immune cells known as macrophages. Woulfe is comparing these cells from people with Parkinson’s disease to the macrophage cells of people who do not have Parkinson’s, to see if the cells behave differently.

“What these macrophages do is eat up abnormal proteins and try to get rid of them,” Woulfe explains. “But if we see differences in either the number of these immune cells, or their distribution, or their shape, it could show us that in people with Parkinson’s disease, the immune cells are having trouble getting rid of the abnormal proteins.”

Woulfe’s theory is that the process by which immune cells break down clumps of protein in the appendix is abnormal in Parkinson’s patients. This allows these clumps to spread along the nerves from the gut into the brain.

If Woulfe can gather evidence supporting this theory, it would provide a crucial window of opportunity to intervene early with drugs or another therapy to activate the immune cells. The goal would be to halt the spread of Parkinson’s long before motor symptoms appear. “Because once a person has motor symptoms, it means that 75 percent of those motor neurons are gone. So it’s way too late,” Woulfe says.