The value of basic research: Discovering links to Parkinson’s

Geoffrey Hesketh, Cell biologist
Geoffrey Hesketh, Cell biologist

The beauty of basic research is that sometimes, when you’re not looking for it, you make a discovery that answers a critical question in an entirely new or different field.

That’s what happened to Geoffrey Hesketh. Hesketh, a cell biologist, was investigating how proteins move around in cells to arrive at their surface in the correct order required to do their jobs.  He was concentrating on the Retromer proteins, a group of proteins that work together to pick transport proteins from their starting point to the correct spots that allow them to send and receive communications signals.

Other researchers had already figured out that damaged forms of one particular protein in the group – a protein called VPS35 – lead to Parkinson’s disease. Hesketh’s work revealed that nine other genes associated with Parkinson’s disease are also part of the Retromer group. That discovery points to this group of proteins as being critical players in the cause of Parkinson’s disease.

One theory is that any defect in the Retromer pathway results in fewer proteins getting to the right spots on the surface of brain cells. That could disrupt communication among the cells. Cells that produce dopamine – the chemical in the brain that affects movement – could be more susceptible to this disruption.

“Or it just could be that after losing their connections with the neighbouring cells, these cells (with damaged Retromer proteins) just shrivel up and die,” Hesketh says.
Knowing exactly what goes wrong at the cellular level is critical for the design of any future drug to treat Parkinson’s, says Hesketh.

Now Hesketh, who has switched the focus of his project to Parkinson’s, uses a technique called mass spectrometry to screen all the proteins in the Retromer group. He wants to identify all the proteins they communicate with, because they could also be implicated in Parkinson’s disease. (Genes make proteins to perform functions.)

Hesketh is now more than halfway through a two-year, $100,000 Basic Research Fellowship from the Parkinson Canada Research Program to pursue this research at the Lunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital in Toronto.

At this point, he’s most excited about the discovery of molecular insights into the “membrane targeting” or clumping of alpha-Synuclein (a-Syn), a gene at the very centre of Parkinson’s disease, and long suspected in the formation of Lewy bodies.

“Knowledge of the precise mechanism of a-Syn membrane binding would be of significant value to the Parkinson’s research community and has the potential to lead to new treatments,” says Hesketh.

Another aim of his work is to complete a “BioID,” and mass spectrometry, of all of the genes known to be associated with Parkinson’s disease, about 50 in total – so far. He is collaborating with Drs. Ted Fon and Heidi McBride of the Montreal Neurological Institute at McGill University, who also have relationships with Parkinson Canada. (Dr. Fon is a previous Chair of our Scientific Advisory Board.)  He is also investigating with them on how the various genes and their proteins impact the quality of a cell’s mitochondria, its energy source.

Hesketh is passionate about the need for basic research and its unintended consequences. “Parkinson’s found me, rather than the other way around,” he says. “I was looking into a pathway that I was pursuing out of curiosity. After a couple of years, we stumbled upon this connection to Parkinson’s disease that probably never would have been found, if we hadn’t gone down this curiosity-driven path. The discovery provided a new framework to my research.”

He’s a good example of how basic science research expands our knowledge base and can lead to potential new avenues of exploration and possible clinical applications.

“My research aims to characterize the interactions made by Parkinson’s-associated genes with the goal of identifying cell pathways and functions central to the development and progression of Parkinson’s disease. This investigation offers great promise in discovering the fundamental cause of Parkinson’s, and I believe, offers our best shot at ultimately finding a cure.”

You can watch our previously recorded interview with Hesketh.  You can also read about other researchers funded by the Parkinson Canada Research Program on our website at www.parkinson.ca.

Preventing brain cells from running out of fuel

Dr. Wei Yi
Dr. Wei Yi

Most of our body’s cells contain mitochondria, small components crucial to ensuring that a cell obtains adenosine triphosphate (ATP), a molecule that provides essential chemical energy for biological functions. When mitochondria are damaged, a cell must remove them before they contaminate it, which can lead to cell death.

“It’s really important to get rid of these mitochondria so that the cell can continue to make use of ATP,” says Wei Yi, a post-doctoral fellow at McGill University’s Montreal Neurological Institute. “It’s a question of making the most of this vital resource.”

Wei Yi was recently awarded a two-year, $80,000, Basic Research Fellowship from Parkinson Canada Research Program. Yi’s research focuses on how damaged mitochondria are handled by neurons carrying dopamine, the complex agent that codes signals for movement control in the brain.

She developed an interest in neurodegenerative diseases like Parkinson’s while studying for her PhD at the Chinese Academy of Sciences.  “I am also interested in the aging population of China, where larger numbers of people are likely to be affected by these diseases.”

Like other cells, neurons regularly remove all kinds of waste material, including mitochondria. This process, known as autophagy, is a rapidly expanding frontier in many areas of medicine. In the case of damaged mitochondria, an enzyme called PINK1 identifies and isolates these components in preparation for disposal. However, in as many as half of patients suffering from early onset Parkinson disease, PINK1 is itself damaged. It can no longer direct the removal of mitochondria.

“When this happens PINK1 is not actually protecting the cells,” Yi says. “They can end up with bad mitochondria and they will die from a lack of energy.”

As part of learning more about this problem, her research has revealed another enzyme, called MPP, which appears to control PINK1.

“By understanding this mechanism, we can find the pathways that could activate them again,” she explains. “If we can determine the relationship between PINK1 and MPP, it will provide a new way of treating Parkinson disease.”

Read about other researchers recently funded by the Parkinson Canada Research Program by visiting the research section of www.parkinson.ca.

Making connections closer to home

Community Development Coordinators
Community Development Coordinators

Are you a caregiver and need someone to listen to you for a few minutes or connect you with respite care services? Would you welcome the chance to meet with others like you living with Parkinson’s? Are you looking for a Parkinson’s exercise class in your community?

Whether it’s helping you to navigate what you need within the healthcare system or connecting you with education, support and comradery within your community, Parkinson Canada is growing to serve you better.

Across Canada, community-based individuals, called Community Development Coordinators, work with individuals like you in your community to connect you to Parkinson support groups, education sessions and local services. In speaking with you, they may be able to determine the availability of existing services and assist in defining gaps. They also build relationships with local members of provincial legislatures  and municipal representatives to advocate for issues important in your local Parkinson community. Most importantly, they build a local volunteer, service and funding network, with you at the centre. No two communities are the same, so the kinds of programs and services will vary.  What we know for sure is that as the population grows and ages, there is always a need.

Recently, Parkinson Canada received a grant for $637,300.00 from the Ontario Trillium Foundation to fund the expansion of our service delivery in the province by adding three new community development positions for the next three years: Margaux Wolfe, based in Ottawa will serve Eastern Ontario; Marielle Henderson, based in Thunder Bay will serve North West Ontario; and Paul Scibetta, based in Brantford, will serve Southwestern Ontario. We have received many requests from individuals and families in these areas, and now, with the new staff, you have additional community resources who can help you live well with Parkinson’s.

As many as 40,000 Ontarians live with Parkinson’s. This initiative aims to alleviate social isolation and create connections for more than 1,200 people. Even in mid-size communities, ranging from 20,000 to 100,000, access to Parkinson’s programs and services may be difficult. By linking individuals with appropriate programs and services, the daily challenges of Parkinson’s can be better managed. Now, there is help and hope closer to home.

Across the country, staff and volunteers, serve communities in a similar fashion. If you, or someone you know, are looking for answers or support, connect with Parkinson Canada. We encourage you to reach out and make a connection.

A great place to start is www.parkinson.ca. Use the map to “Find help near you.” You’ll find contact information for local offices, events and activities, including support group meetings, educational conferences and exercise classes. Also, you can find a wealth of fact sheets and other resources. If you have a bit more time, why not watch webinars and listen to podcasts, available any time you need them; simply access the website at a time convenient to you.

If you prefer to speak to someone, call our Information and Referral Centre at 1-800-565-3000. And if you are asked to leave a message, please do so.  Our trained and compassionate associates will respond to you as quickly as possible.

Annual Saskatchewan fundraiser surpasses half-a-million dollar mark

Travis Low, right, presents the 2016 proceeds to Marlin Stangeland and Todd MacPherson, Parkinson Canada.
Travis Low, right, presents the 2016 proceeds to Marlin Stangeland and Todd MacPherson, Parkinson Canada.

Congratulations to the more than 6,000 participants, volunteers, sponsors and community members in Saskatoon, Saskatchewan, who have come together during the past eight years to be part of the annual Lows in Motion fundraiser.  The community event raises funds to improve the lives of people living with Parkinson’s in Saskatchewan. Including the 2016 event held in November, they have raised a total of $516,000.

Over the years, the Lows in Motion contributions have helped Parkinson Canada hold five annual education conferences in the province; expand the number of support groups in Saskatchewan to 13 – most holding monthly meetings; and make annual contributions to the Parkinson Canada Research Program, which has funded more than 500 Parkinson research projects, totaling more than $26 million, since 1981.

Travis Low founded the event in 2009 in honour of his grandfather who had Parkinson’s disease and his father who was newly diagnosed at that time. Lows in Motion generously donates all proceeds to Parkinson Canada to continue to bring help and hope to people living with Parkinson’s.

“There is so much to be hopeful for though. Hope that we will continue to progress our understanding of the disease. Hope that new treatments will allow those living with the disease to live a better quality of life,” says Travis. “And the biggest hope that we will one day find a cure!”

The annual event is more than your typical gala; supporters are treated to first class entertainment, while knowing they are giving to a great cause.  And they get to learn about what life with Parkinson’s is really like. You can check out two moving videos from Lows in Motion: Beneath the Tremors, which debuted at the 2015 event, as well as the most recent video Smiles of Hope.

Make a note in your calendar and watch for details about the next Lows in Motion shaker event in November, 2017.