Scott Ryan’s Parkinson’s stem cell research garnering international recognition

Dr. Scott Ryan

When Scott Ryan travelled to Sweden earlier this year, he was keen to share the Parkinson’s research results from his small lab team at the University of Guelph. He was even more thrilled to have his poster presentation be one of five winning posters, out of 1,700, at the International Society for Stem Cell Research conference.

A native of St. John’s Newfoundland, neuroscientist and assistant professor Ryan, 35, last year received a two-year, $90,000, Pedaling for Parkinson’s New Investigator Award through Parkinson Society Canada’s National Research Program. Now at the halfway point, his project is gaining international interest.

In the quest to discover what’s killing the dopamine-producing cells whose death results in Parkinson’s disease, Ryan is honing in on a group of proteins that turn signaling networks in the brain on and off. He is concentrating on the balance between cell generation and degeneration, and on finding ways to reverse the latter. Ryan uses a model of Parkinson’s disease derived from the skin of a patient with a familial form of Parkinson’s. Once in culture, the donor cells were reprogrammed into stem cells and researchers were able to correct the genetic mutation that caused the disease, in this case a mutation in the alpha-synuclein gene.

Ryan is using this model and system to identify a family of proteins, called transcription factors, in dopamine-producing cells. He describes these proteins – including one called MEF2 – as a “pro-survival team” that can keep the dopamine-producing cells alive.

If disease mutations or environmental contaminants like pesticides or herbicides evoke stress in the energy-producing portions of the cells called mitochondria, the stress can turn off the survival team’s signaling network and block their ability to keep dopamine producing cells alive.

“The more stress that builds up, the more you deactivate (the proteins) until you reach a critical level, and the cell dies,” Ryan explains.

By working with a drug discovery and development group, Ryan hopes to test different compounds on the stem cell model of Parkinson’s disease, to find one that will turn the pro-survival signaling network he has discovered back on. He hopes his discoveries will apply to both familial forms of Parkinson’s disease – something that runs in his own family – and non-familial, or sporadic, forms.

“It really doesn’t matter why you have Parkinson’s, because what’s defective seems to be common in all forms, at a cellular level,” Ryan says.

Because Ryan’s work involves a model made from Parkinson’s disease patient cells, he hopes his discoveries will be easier to move to the clinic to help treat patients, compared with animal models of drug discovery.

“Translating it to humans will be less of an issue,” he predicts.

Ryan’s research career has progressed steadily, with every step contributing to the work he is doing today. And PSC’s National Research Program has played an important supporting role in his development. His fourth-year research project on how fatty acids affect signaling in cell and gene expression sparked his interest in continuing in the research field. Subsequent supervisors and mentors in Ottawa and California helped hone his skills.

“My Ph.D. supervisor Steffany Bennett at the University of Ottawa was instrumental in training me in how to approach research problems and how to think about science,” he says. “That’s also when I began studying neuroscience and I was drawn to Parkinson’s disease.”

The interest in Parkinson’s disease reaches back to his family roots in St. John’s. His grandfather and his great uncle both had Parkinson’s. “Until I was 10, I spent time after school at my grandparents’ house, just up the street,” he says.

After completing his Ph.D. Ryan was well-prepared to work with his next mentor Dr. Rashmi Kothary at OHRI (Ottawa Hospital Research Institute), who was studying several movement disorders. “He was associate director of the Institute and I was given the freedom to explore my own ideas and follow through,” says Ryan. He investigated the molecular underpinnings of a type of dystonia.

Funding from PSC’s National Research Program enabled Ryan to complete an international stint at the renowned Sanford Burnham Medical Research Institute (now called the Sanford Burnham Prebys Medical Discovery Institute) with neurologist and scientist Dr. Stuart Lipton.

“Dr. Lipton developed one of the only drugs currently in use for advanced Alzheimer’s disease,” says Ryan. “And his lab was run very much like an industry lab, conducting research and translating the results for therapeutic use. They were doing patient-derived stem cell research and I was able to apply this to my own work.”

Ryan began working on Parkinson’s disease in California with a large team of about 40 people. “In addition to the research, I learned to work with industry stakeholders, an increasingly important skill for researchers,” he says. A publication in the respected journal Cell was a significant accomplishment from this time.

Now at the University of Guelph, Ryan has his own lab, including a lab manager and post-doctoral, graduate and undergraduate researchers. The Pedaling for Parkinson’s New Investigator Award from Parkinson Society Canada’s National Research Program has helped make this a reality. In addition, he’s been able to parlay his earlier successes with PSC funding into another large, and unique funding partnership through the University of Guelph. The Ontario Ministry of Agriculture, Food and Rural Affairs, and the Grain Farmers of Ontario have granted him $300,000 over three years to explore whether dietary Omega 3 and 6 fatty acids reduce the risk of Parkinson’s disease.

“Research in Parkinson’s is definitely accelerating, driven in large part, by stem cell research and international collaboration, Ryan says. “This disease is an excellent candidate for a stem cell application. We know the location in the brain that is affected; we know that neurons are dying. And there is a large enough patient population that there is public interest, political will, interested funders and the potential to make a substantial impact on human health. It cannot be long now, before we find both lifestyle treatments and new drug treatments to prevent Parkinson’s and eventually alleviate its symptoms.”

To find out more about current and past projects funded through Parkinson Society Canada’s National Research Program, click here.