Feb 23, 2022

Two Scientists Receive Inaugural Awards to Lead New Parkinson’s Research

By Andrea Haman

Two University of Toronto scientists are winners of inaugural awards toward innovative research into Parkinson’s disease within the Tanz Centre for Research in Neurodegenerative Diseases. The researchers are leading new studies to better understand Parkinson’s disease, which affects up to two per cent of people by age 65 and for which there is no cure.

Professor Ekaterina Rogaeva is the recipient of the Robert L. Cunningham Parkinson’s Research Award, funded through a $1-million gift honouring the late Robert Cunningham, a mentor and coach to many people in business, sports and other facets of his life.

Professor Anurag Tandon is the recipient of the Laura Sabia Award, celebrating the late Laura Sabia, who was awarded the Order of Canada in 1974 for her many contributions to advance women’s equality and rights.

“We are honoured that these awards have been entrusted to the Tanz Centre to support new Parkinson’s research,” says Professor Graham Collingridge, director of the Tanz Centre. “These awards enable our scientists to carry out highly innovative research toward our long-term vision to prevent and find ways to treat Parkinson’s disease.”

Ekaterina Rogaeva

Zeroing In on Aging — from a New Angle 

Ekaterina Rogaeva is focusing on aging from a new angle: DNA modifications linked to aging, or DNA aging.

“I am interested in DNA aging because the strongest risk factor for developing Parkinson’s disease and any other neurodegenerative condition is aging,” says Rogaeva. “But chronological age doesn't help very much because we all, based on chronological age, have a similar pace of aging. This is not true. Some people age faster.”

Earlier research has shown that DNA modifications at specific locations within the genetic makeup of humans, or the human genome, are involved in DNA aging. Rogaeva and Professor Anthony Lang are studying 350 genes — out of the 25,000 genes in the human genome — in a combined way to calculate DNA aging.

Their goal is to test if DNA aging is linked to the age of onset of Parkinson’s disease, for example, if people with accelerated DNA aging are more likely to develop Parkinson’s disease at an earlier age.

This new research expands on a study underway by Rogaeva, which is examining DNA aging and the age of onset of a condition called rapid eye movement (REM) sleep behaviour disorder. Since the majority of people with this disorder will develop Parkinson’s disease within 12 years, the onset of the disorder may present a unique opportunity to intervene before Parkinson’s symptoms develop.

“With the Robert L. Cunningham Parkinson’s Research Award, we can now look at both sides: before and after Parkinson’s disease appears,” says Rogaeva.

In the short term, Rogaeva says the research will identify if there are different groups of individuals, based on DNA aging, that may be useful to consider differently for future research. Over the long term, understanding DNA aging may help to answer important questions, says Rogaeva, such as: “When do we need to treat Parkinson's disease is it better to start earlier, before the symptoms appear? And can we slow down DNA aging?”


Solving a Mystery: One Protein, Three Diseases

With the support of the Laura Sabia Award, Anurag Tandon is aiming to solve a mystery: How does one protein lead to three separate neurodegenerative diseases?

In Parkinson’s disease, Lewy body dementia and multiple system atrophy (MSA), the protein alpha-synuclein misfolds and builds up as harmful sticky deposits that eventually damage nerve cells, or neurons, in the brain.

An important clue came from research led by Associate Professor and Tanz Centre scientist Joel Watts and published in a 2019 paper in Nature Neuroscience. Watts and colleagues created alpha-synuclein molecules with different shapes and compared their effects on neurons in different brain regions in mice. They found that neurons in specific brain regions are sensitive to different shapes, and the different shapes accumulated as buildups characteristic of separate diseases.

“We can try to stack forks and spoons together, but it doesn't work well unless they're the exact same type of cutlery,” says Tandon. “To date, my lab's been throwing all the cutlery at the neurons to answer this question. Now, we are breaking it down into individual types.”

Specifically, Tandon and his team will study how these different shapes result in these differences, for example, what each shape binds to and how it spreads inside neurons. The team will conduct their research in cell cultures of neurons from two brain regions: the hippocampus and the midbrain.

“The Laura Sabia Award provides pilot funding for us — this will tell us within a year if our approach works,” says Tandon. “We’re seeing promising early data.” (See image below.)

The goal is to uncover a location possibly a cell-surface receptor for alpha-synuclein or a pathway between neurons where it may be possible to intervene to stop the development of Parkinson’s disease, Lewy body dementia or MSA. This would drive future research to develop or explore potential treatments. “That would be quite exciting,” says Tandon.

alpha-synuclein strain

In their research supported by the Laura Sabia Award, Anurag Tandon and his team added an alpha-synuclein strain (shown in red) to hippocampal neurons in a cell culture. Over time, harmful buildups of misfolded alpha-synuclein (in green) — which are hallmarks of Parkinson's disease and other diseases — form around the cell nucleus (in blue).