University of Ottawa (Ottawa Hospital Research Institute)
New Investigator Award: $90,000 over two years
Critical role of Parkin as an anti-oxidant in mitochondria; new concept of Parkin function
Although the parkin gene has been identified as critical to the development of early-onset Parkinson’s disease, researchers still do not know exactly what role it plays within cells and in cell death. At the University of Ottawa, Dr. Tohru Kitada, a neurologist, is investigating the way parkin interacts with mitochondria, the parts of cells that generate energy and oxidative stress.
Kitada was a leading researcher on the original team in Japan that identified the parkin gene. Now, he’s using embryonic fibroblasts from mice to try to pinpoint the role of missing parkin in forcing mitochondria to generate oxidative stress, the process within cells that produces reactive oxygen molecules and can damage brain cells.
Kitada wants to know why dopamine-producing cells seem particularly susceptible to damaged mitochondria, since those cells are essential to keeping brain cells signalling and communicating well. Recently, research has also linked parkin to the ability of cells to maintain appropriate calcium levels and membrane potentials, something that could also contribute to cell death.
To try to stabilize mitochondria within brain cells and to prevent cell death, Kitada will test a combination of two drugs, Glutathione and Zonisamide, which is approved in Japan but not North America, to treat Parkinson’s disease. “Nobody has tried such kind of combination therapy,” Kitada says. “I hope it has a synergistic effect.”
If the combination therapy is effective in the cell cultures, the next step will be to test it on mouse models of Parkinson’s. If the therapy proves successful, using Glutathione and Zonisamide, which have already been studied and approved in at least one market, would hasten the regulatory process for their potential use for people with Parkinson’s in North America.
Kitada’s research has been motivated by his clinical work with patients, both of which he is continuing in Ottawa. “If possible, I’d like to stay here in Canada,” Kitada says. “I can do exciting research in North America.”