Easing the pain of Parkinson’s

Dr. Susan Fox

Pain is a constant companion for as many as 10 percent of people with Parkinson’s disease. Unfortunately, most of them can’t tolerate the sleepiness and confusion regular pain medications induce.

That’s why Dr. Susan Fox, a Toronto neurologist and professor at the University of Toronto, is investigating a different source of pain relief. Fox is conducting a pilot study, along with her colleague Dr Tiago Mestre in Ottawa, to see whether 15 people with Parkinson’s disease will benefit from oils made from cannabinoids – the active compounds in marijuana.

Currently, people with Parkinson’s may experience pain in their muscles and joints because of the stiffness and rigidity the illness causes. Some also report a sharp pain, often in their legs or feet, that is more puzzling because doctors can’t determine its exact cause.

“Some people call it central pain,” says Fox. “It’s probably mediated by some brain mechanism reflective of Parkinson’s. People express this as an unpleasant burning, stabbing pain, and it’s very difficult to treat.”

Fox, who treats people with Parkinson’s at Toronto Western Hospital’s Movement Disorders Clinic, hopes her study will discover whether people with Parkinson’s can tolerate oils, and experience less pain after using them. She also wants to identify the best strength and dosage for people to use.

Almost every day, one of her patients asks her about trying marijuana to relieve their tremors or rigidity.

But although marijuana might help people relax and feel less rigid temporarily, there’s no evidence that it relieves those symptoms long-term, she says.

“There’s always this misconception that cannabis can help anything and everything,” she adds.

Fox would rather see her patients try approved and safe medications to relieve tremors and rigidity, so that’s why this study is focused on determining if there is any benefit of  cannabis oils to treat pain.

Fox’s study will also assess whether these oils cause drowsiness and lower blood pressure – already a concern for people with Parkinson’s. There is also a small risk the oil could induce or worsen hallucinations – a symptom some people are already experiencing.

If Fox’s research demonstrates that people can tolerate cannabis oil and it doesn’t have worrisome side-effects, then her results could lead to a larger, randomized controlled trial.

“There are clear risks and side effects with cannabis, so you weigh up the risk versus the benefit ratio,” she says.

Most importantly, Fox hopes the cannabis oil will not only help people with Parkinson’s feel better, it will also relieve a burden for their caregivers.

“It’s an unmet need,” she says. “It’s very challenging for the family, as well, to watch their loved one in pain and agony.”

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


Improving damage detection in the brain

Professor Jean-François Trempe

A pair of proteins, whose malfunction is associated with Parkinson’s disease, normally work together to fulfill valuable housekeeping chores within the body. They keep brain cells healthy, for example, by discarding dead or dying material inside them. But these proteins have to be tightly controlled, because if they “help” too much, they can become harmful. When they aren’t regulated, the damaged proteins end up killing the brain cells they were designed to save.

“It’s like having a bulldog on a leash,” says Jean-François Trempe, an assistant professor at McGill University’s Department of Pharmacology and Therapeutics. “You have to keep it under control.”

A decade ago, Trempe began studying Parkin, one of the most powerful of these proteins.

“Parkin is a protein that can destroy parts of the cell, so you don’t want it to be active all of the time,” Trempe says.  “You only want it to get rid of the bad parts of cells.”

Parkin’s activity is controlled by another protein, a gene called PINK1. PINK1 constantly enters the  mitochondrion, an internal part of the cell that oversees the production of energy. When the mitochondrion is healthy, it simply eliminates PINK1. If it is malfunctioning, however, PINK1 builds up within brain cells, which serves as a signal to Parkin to move in and eliminate them.

The disruption of mitochondrial function is a hallmark of Parkinson’s disease, which has led Trempe to regard PINK1 as a key to understanding this process. Other cells in the body are also susceptible to mitochondrial damage, he says, but they manage to recover successfully. Those brain cells that do not recover appear to be under stress, and thus are more sensitive to the loss of PINK1.

“This is what I find fascinating — why a mutation in a gene that you find everywhere only causes the loss of a subset of neurons,” he says. “This is what we think is happening.”

There are very few genes like PINK1 in the body, which makes it all the more interesting to study. If specific compounds can be identified to stabilize PINK1 so bad mitochondria are more readily detected and removed by Parkin, the result could allow these cells to repair themselves, fending off the onset of Parkinson’s disease.

“We need to confirm this idea (of cell reparation), which is why we are conducting this proof-of-concept study,” says Trempe. “It will be a tool that should lead us to some very effective strategies.”

Dr. Trempe’s 2 year Pilot Project Grant is funded by Peter Cipriano through the Parkinson Canada Research Program.

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


Make 2018 Your Parkinson’s Year

webinar imageHave you committed to making 2018 the year you learn how to live your best with Parkinson’s? If so, Parkinson Canada has another productive, event-packed year that continues to bring help and hope to those of you living with Parkinson’s across Canada.

The newly redesigned Parkinson Canada website at www.parkinson.ca is a tremendous resource for you, your family and your care team to quickly and conveniently access everything from online informational resources (facts sheets, handbooks, etc.), local education and fundraising events, and support groups in your community. The website is also your central hub to register and replay webinars presented by some of Canada’s leading PD experts.

Expert Webinar Series – 2018

Be sure to mark your calendars for these upcoming webinars featuring experts and topics you will not want to miss:

How to Keep Intimacy Alive in Parkinson’s Disease

Tuesday, February 13

 Live-Stream in Person Event highlighting Parkinson’s Disease: An Introductory Guide

Friday, March 16

Falls Prevention 365 Days a Year

Tuesday, May 8

Advanced Parkinson’s Therapies: DBS and Duodopa

Tuesday, June 12

Alternative Parkinson’s Therapies: Music & Dance

Tuesday, August 14

Parkinson’s Toolbox: All You Need to Manage PD

Tuesday, September 11

PSP and Multiple System Atrophy (MSA) – Signs, Symptoms and Treatment

Tuesday, November 13

Incontinence and Voiding Dysfunction in PD

Tuesday, December 11

Podcasts with Parkinson Canada’s Information and Referral Specialist

Robert TerSteege
Robert TerSteege, Parkinson Canada

Complementing the expert webinar series this year, Parkinson Canada Information and Referral Specialist, Robert TerSteege, will provide comprehensive information on the spectrum of Parkinson’s disease.

January: Early Stage Parkinson’s

April: Mid-Stage Parkinson’s

July: Late-Stage Parkinson’s

October: Caregiving through the Stages of Parkinson’s

All webinars and podcasts are at no charge to register, and further information can be found online by visiting The Knowledge Network on the Parkinson Canada website at: www.parkinson.ca/knowledge.


Establishing a new link between brain and body

simon wing image
Dr. Simon Wing,
McGill University

A disease of the brain can become a disease of the entire body, as the breakdown of neural pathways often leads to a loss of muscle mass. Dr. Simon Wing, a professor in McGill University’s Department of Endocrinology and Metabolism, is eager to examine this potential connection as it applies to Parkinson’s disease. He has only recently discovered the possibility of such a link, but it could offer a new perspective on some of the most fundamental aspects of this condition.

“Through my research over the last 15 years I found a gene that encodes an enzyme that appears to be important in muscle wasting,” he explains. “This gene is called USP19.”

Wing was already studying the behaviour of this gene when he was contacted by a U.S. researcher who discovered that USP19 may also be tied closely to a problematic aspect of Parkinson’s disease. At the heart of this problem is a protein called α-synuclein, which forms clumps of disruptive material within brain cells. Not only does this material interfere with the ability of these cells to produce dopamine, these affected cells also appear to transmit α-synuclein to other brain cells, so that the disease spreads and causes more disability.

“Our work is based on a model where Parkinson’s disease spreads because α-synuclein is transferred from a sick neuron to a healthy neuron,” says Wing, recipient of a one-year $45,000 Porridge for Parkinson’s (Toronto) Pilot Project Grant. “However, nobody really knows how α-synuclein gets out of the neuron.”

That detail is crucial, because if researchers can identify and block the transmission mechanism, it might be possible to design a treatment to stop α-synuclein from leaving affected cells – stopping Parkinson’s in its tracks.  Wing’s U.S. colleague was therefore interested in USP19, which appears to serve as a mediator of this process. More importantly, Wing’s laboratory was already home to mice that have been genetically altered to remove USP19.

“If we look at our mice that do not have USP19 and so presumably cannot use this pathway to push α-synuclein out of the neuron, are they protected against the progression of Parkinson’s disease?” asks Wing. If so, then this finding would pinpoint this gene as a valuable target for possible therapies.

Wing admits that this prospect remains an open question, but one worth exploring because of its novelty and exciting possibilities. He also acknowledges that this foray into Parkinson’s disease has been a learning experience for him, one that has led him to work with some of the top people in the field at the Montreal Neurological Institute.

“It could be quite transformative,” he concludes. “There are groups already working on developing drugs to block USP19. We could be able to move fairly quickly over a few years into clinical trials if our hypothesis is correct.”

Editor’s note:

The most recent Porridge for Parkinson’s biennial event was hosted on November 12, 2017 in Toronto, raising in excess of $200,000. Proceeds from this year’s event support four grants through the Parkinson Canada Research Program, in addition to the novel work of Dr. Wing with the USP19 gene, the following researchers and projects will benefit from the support of Porridge for Parkinson’s (Toronto):

  • Dr. Alexandre Boutet – two-year Porridge for Parkinson’s (Toronto) Graduate Student Award in Honour of Isabel M. Cerny
  • Cricia Rinchon – two year Porridge for Parkinson’s (Toronto) Graduate Student Award in Honour of Delphine Martin
  • Anita Abeyesekera – two year Porridge for Parkinson’s (Toronto) Graduate Student Award

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


Sniffing out Parkinson’s disease

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Dr. Johannes Frasnelli, Université de Montréal at Trois-Rivières

Losing their sense of smell is an early symptom that most people with Parkinson’s disease experience. That’s why some researchers are targeting the olfactory system, to use it to predict who will develop the disease.

Because there are many other reasons besides Parkinson’s that people lose their sense of smell, however, Dr. Johannes Frasnelli is hoping another sensory system will provide better diagnostic clues. Frasnelli, a neuroscientist and professor at the Université de Montréal at Trois-Rivières, is focused on the trigeminal chemosensory system. The trigeminal system – which most people aren’t even aware they use – is a part of the nervous system that helps us perceive the spiciness of hot peppers or the freshness of peppermint.

Frasnelli is trying to pinpoint patterns of impairment affecting the trigeminal system that are specific to Parkinson’s disease. Recognizing that pattern could form the basis of a diagnostic test or marker.

“The benefit of early detection would be to develop tools so we could at least stop the progress of this disease,” Frasnelli says.

The trigeminal system consists of receptors in the nose and mouth that are independent of our sense of smell and taste. Typically, though, someone who has lost their sense of smell would also become less sensitive to spiciness, burning and cooling sensations.

But Frasnelli suspects people with Parkinson’s disease do not have a reduction in the trigeminal system, meaning they can still perceive those sharp and spicy sensations. He’s comparing groups of people who have lost their sense of smell for another reason to those with Parkinson’s disease, and to healthy people, to try to isolate a unique pattern or profile of those who are at risk of developing Parkinson’s.

If he discovers that people with Parkinson’s can’t smell most odours but can still perceive the fresh, burning or spicy sensation, testing that might provide a good diagnostic marker.

“We will then have a better way of evaluating who is most at risk and those who are less at risk,” Frasnelli says.

That evaluation is critical because by the time Parkinson’s is diagnosed, most people have already lost 60 percent of their dopamine-producing brain cells.

Frasnelli, who trained as a doctor in Germany, prefers research to clinical work with patients because he can satisfy his curiosity about problems that affect people, including those with Parkinson’s he says.

“With research, you can ask questions where there is no answer, and you have to find the answer yourself,” he says. “That’s extremely interesting.”

Dr. Johannes Frasnelli received a one-year, $40,000 Pilot Project Grant for his research about chemosensory impairment in Parkinson’s disease. Read about other researchers recently funded by the Parkinson Canada Research Program by visiting the research section of www.parkinson.ca.