Oct 13, 2022

Three Scientists Receive Tanz Centre Research Awards

Watts, Visanji, and Schmitt-Ulms
Joel Watts, Naomi Visanji, and Gerold Schmitt-Ulms
By Eileen Hoftyzer

Three researchers at U of T’s Tanz Centre for Research in Neurodegenerative Diseases have been awarded $40,000 each to conduct research into Parkinson’s disease and other neurodegenerative conditions.

Two of the projects tackle different challenges associated with a protein that misfolds and accumulates in the central nervous system of people with Parkinson’s disease, and the third is examining a protein involved in prion diseases.

“These awards allow our scientists to examine important questions about how neurodegenerative diseases start and progress,” says Graham Collingridge, director of the Tanz Centre. “We’re grateful for the donor support that has made these awards possible.”

Robert L. Cunningham Parkinson’s Research Award

Joel Watts, associate professor in the department of biochemistry and scientist at the Tanz Centre, received the Robert L. Cunningham Parkinson’s Research Award to investigate whether differences in the misfolding of the alpha-synuclein protein results in the patient-to-patient variability seen in Parkinson’s disease.

I am extremely grateful to receive this award,” says Watts. “These funds will allow me to perform preliminary experiments to see if our ideas are feasible, hopefully leading to bigger grants in the future. Awards like this are critical for sustaining research into the fundamental science of neurodegenerative diseases such as Parkinson’s.”

Parkinson’s disease is one of a group of diseases in which a protein called alpha-synuclein misfolds and accumulates in nervous system cells. Patients with Parkinson’s disease can have very different clinical presentations, and one hypothesis is that differences in how the alpha-synuclein protein folds (known as a “strain”) may lead to differences in the disease course or presentation.

With this new research award, Watts will generate two different types of misfolded alpha-synuclein protein and use them as “seeds” to induce disease in healthy mice. He will then look for strain-specific differences in where and how the protein accumulates in the central nervous system and examine whether this model reflects what happens in human disease.  

Our ultimate goal is to be able to accurately reproduce all the key hallmarks of Parkinson’s disease in a mouse,” says Watts. “This would be extremely useful for identifying and testing therapies capable of blocking the progression of disease in people with Parkinson’s.”

Laura Sabia Parkinson Research Award

Naomi Visanji, assistant professor in the department of laboratory medicine and pathobiology and scientist at the Tanz Centre, is also investigating the alpha-synuclein protein and whether different strains of the misfolded protein can explain the variability in Parkinson’s disease and similar disorders. She recently received the Laura Sabia Parkinson Research Award to study the “seeding” activity of different alpha-synuclein strains.

Misfolded alpha-synuclein is able to “seed,” or cause healthy alpha-synuclein to misfold, essentially spreading the misfolding throughout the central nervous system. Previous research has shown that different strains of misfolded protein may have different seeding activity — for example, strains with a stronger seeding capacity may lead to a more aggressive disease — but this needs to be explored further.

“We believe there are aggressive forms of alpha-synuclein that lead to the rapidly progressive disease seen in some patients and less aggressive forms of the protein that may drive a more protracted disease course in others,” says Visanji, who is also a scientist at the Krembil Research Institute, University Health Network.

“If this is true, we can explore the different mechanisms that underly disease severity and progression and gather critical information to help develop more personalized treatments for patients with different forms of Parkinson’s disease.”

With the Laura Sabia Parkinson Research Award, Visanji will extract different strains of alpha-synuclein from high seeding and low seeding patients and seed them in mice to analyze the activity of the different strains.

The project will provide important evidence of how different strains of alpha-synuclein influence disease variability.

As an early career researcher and new principal investigator at Tanz, receiving this award is particularly impactful,” she says. “First, it provides valuable funding to support my lab at this early stage. Second, being selected by a committee of my peers provides me with confidence in the value of my ideas as I begin to pursue my independent research program.”

Kofman Family Memorial Research Award

Gerold Schmitt-Ulms, professor in the department of laboratory medicine and pathobiology and scientist at the Tanz Centre, is the inaugural recipient of the Kofman Family Memorial Research Award.

With the award, Schmitt-Ulms is examining whether a class of drugs called cardiac glycosides, which are used to treat heart failure and irregular heartbeat, has potential to treat prion diseases or other neurodegenerative diseases.

In previous research, the Schmitt-Ulms team found evidence that cardiac glycosides can induce cells to destroy prion proteins, which could help to improve survival of patients with prion disease. The new award will contribute to early studies of whether their candidate molecule that has been optimized for uses in the brain can reduce prion protein levels.

Schmitt-Ulms hopes that his research program will lead to a well-understood class of drugs being used as a potentially low-cost treatment approach, not only for prion diseases but also other neurodegenerative diseases.

If successful, the benefit of reducing prion protein levels may extend to individuals afflicted with Alzheimer’s disease, because prion protein also contributes to toxicity observed in brain cells in this most common dementia,” he says.

We are deeply grateful to the Kofman family for this generous support of our research. This award will bridge a funding shortfall for a half year, allowing us to retain highly qualified personnel until, hopefully, we can secure considerable funding that is urgently needed to evaluate this treatment modality.”