Research Cycle 2018-2020

Individuals with a particular sleep disorder are much more likely to develop Parkinson’s disease, a connection that has provided a unique research opportunity for Dr. Ziv Gan-Or, an assistant professor at McGill University and a researcher in the Montreal Neurological Institute and Hospital. He has recruited more than 1,000 of these individuals from around the world for a study to examine the genetic factors that might link their condition with neurodegeneration. The goal is to identify a genetic marker that would indicate the early onset of Parkinson’s disease in any individual, so that it could be treated as soon as possible.

At the University of Montreal, Professor Louis-Eric Trudeau investigates the earliest potential causes of Parkinson’s disease, at the cellular level. He’s exploring the possibility that Parkinson’s is a form of autoimmune disease, caused when the immune system attacks the axon terminals in our brain cells. Those extremities release the chemical messengers that communicate with other cells, and damage to such terminals may disrupt the dopamine-producing brain cells that are key to Parkinson’s.

Dr. Hideto Takahashi, a researcher at the Montreal Clinical Research Institute, has pointed to a protein called neurexin as a key contributor to neurodegenerative disease. This agent is a building block of synapses, the vital links between neurons that allows these brain cells to communicate with one another. Neurexin also moderates agents associated with the development of Parkinson’s disease and Alzheimer’s disease, making it a good candidate for potential therapies to treat these disorders.

At a specialized laboratory in the Baylor College of Medicine, postdoctoral associate Paul Marcogliese is studying a malfunction in multiple genetic models of Parkinson’s disease in fruit flies. In addition to indicating genetic abnormalities that could indicate an individual’s prospects of developing this condition, the work could reveal targets for potential drug treatments to correct this problem, preventing not only the loss of cell function but perhaps also the onset of the disease.

The Movement Disorders Clinic at Toronto’s University Health Network is among the top clinics in the world for treating Parkinson’s disease. During her fellowship there, Dr. Sarah Lidstone will study ways to improve treatment for people living with Parkinson’s, including studying innovative models of care in Europe and the UK. Her hope is to build a patient-centred network of allied health professionals focused on Parkinson disease that treat the whole patient.

At Dalhousie University, neuroscientist George Robertson is investigating the role of a protein called MCU—mitochondrial calcium uniporter—in Parkinson’s disease. This protein moves large amounts of calcium into energy building blocks within cells called mitochondria. Robertson is determining whether excessive MCU activity in Parkinson’s disease kills brain cells by allowing too much calcium to enter mitochondria. His work could lay the groundwork for a drug that halts the progression of this disease.

Having completed her residency as a neurologist in Vancouver, Melissa Mackenzie is spending an additional year as a fellow in the Institute for Neurology at University College London, a pioneering centre in the treatment of Parkinson’s disease. She intends this experience not only to benefit the way she deals with her own patients, but also to help her develop the expertise to teach and improve clinical standards in the entire field.

Mitochondria are components within most of the body’s cells, where they provide energy necessary for these cells to function. However, the function of the mitochondria itself may be impaired by variants of the proteins CHCHD2 and CHCHD10. When this happens to the neurons that produce dopamine, the result is Parkinson’s disease. Isabelle Straub, a doctoral student at McGill University, studies the normal function of these proteins, and the molecular means by which damaged proteins cause mitochondria to malfunction in brain cells.

At Laval University, PhD candidate Hélèna Denis is looking deep inside the blood cells of people with Parkinson’s disease. She’s examining the connection between proteins linked to Parkinson’s and small pieces of cell membrane, called extracellular vesicles that can emerge from any cell. Eventually, her work could be used to accelerate diagnosis, identify the stages or progression of the disease, and test how well new treatments work.

If researchers could find a non-invasive, physiological tool to diagnose Parkinson’s disease, it might be easier to start treatment earlier. At McGill University, Dr. Mervyn Gornitsky believes he has done just that—by measuring the quantity of a protein called heme oxygenase-1 (HO-1) in samples of the saliva of people who have Parkinson’s. Gornitsky, an oral surgeon, is using his biobank of 4000 saliva samples to confirm the test’s ability to determine the presence of Parkinson’s in people who are in the early stages of the disease, even before they show tremors, stiffness or other motor control symptoms.

One of the difficult aspects of Parkinson’s disease is the lack of easy diagnostic tests. At Queen’s University, PhD candidate Po Yueh (Jeff) Huang is measuring eye movements and the size of people’s pupils as they perform cognitive tasks to examine the link between the eye and neurodegenerative diseases, including Parkinson’s. By correlating pupil size with clinical markers, he hopes to develop a set of non-invasive ways to detect Parkinson’s early, and measure whether drugs or other interventions are effective in treating people with the disease.

Most people with REM sleep behaviour disorder (RBD), which makes them act out their dreams, later develop Parkinson’s disease or related conditions such as multiple systems atrophy or Lewy body dementia. At Western University, Dr. Penny MacDonald, a neurologist and Canada Research Chair, is using imaging technology to check for structural changes in the striatum region of the brains of people with this sleep disorder. If she finds these changes, they could be used to predict who will develop Parkinson’s, and start treatment before motor symptoms emerge.

A combined assessment of eye movements and genetic factors promises to shed new light on drug-related problems in Parkinson’s disease patients. While medication to boost dopamine levels in the nervous system can restore movement control to many patients, this sharp increase in dopamine can also lead to unwanted cognitive changes such as impulsive behaviour followed by an equally sharp crash and general lethargy. An expanded study will look for indicators to identify individuals at risk of entering this cycle.

Research into the causes of Parkinson’s disease increasingly focuses on the interaction among proteins in brain cells. At McGill University, PhD candidate Marisa Cressatti studies the interaction between two proteins, called alpha-synuclein and heme oxygenase-1 (HO-1). If she discovers that HO-1 can accelerate the spread and accumulation of alpha-synuclein, the protein found in clumps in the brain cells of people with Parkinson’s, researchers could target HO-1 as part of a new drug or gene therapy.

Mohamed Eldeeb, a researcher at McGill University, is looking for molecules that regulate a crucial gene linked to the onset of Parkinson’s disease. Using the advanced genome editing approach known as CRISPR, he intends to identify the particular agents that allow cells in the brain to become compromised, so that they no longer produce the dopamine necessary to control the body’s muscle movements. In this way, he hopes to reveal which molecules might make the best targets for therapy to prevent this loss of function.

Université de Montréal researcher Diana Matheoud has identified the way cells respond to infection or stress as a potential indicator of the onset of Parkinson’s disease. Genetic mutations associated with this neurodegenerative condition also affect this immune system process. More specifically, the effects extend to mitochondria, key structures within cells that provide vital energy for their functioning, which are directly compromised by Parkinson’s.

McGill University doctoral student Shafqat Rasool is investigating the way PINK1, a gene related to Parkinson’s disease, is activated. He’s also studying small molecules that could improve the gene’s function. PINK1 tells the body’s cells to remove damaged mitochondria. When this gene fails to do its job, damaged mitochondria accumulate and clump up in neurons, causing their death and eventually leading to Parkinson’s. Rasool hopes to reveal a therapeutic target to address a fundamental cause of this condition.

The protein alpha-synuclein works its way into cells occupying parts of the brain affected by Parkinson’s disease as well as those cells in other parts of the brain that remain healthy. This observation has led researchers like Maxime Rousseaux at the University of Ottawa to consider whether this protein’s presence is harmful or helpful. He intends to resolve this question with a search for the mechanism that leads to this protein toxicity in those brain cells. The result promises to shed new light on the connection between genetic mutations associated with Parkinson’s and the specific behaviour of this protein.

At McGill University, neuroscience and kinesiology student Dorelle Hinton is using imaging technology known as Positron Emission Tomography (PET) to scan the brains of people with Parkinson’s disease who are experiencing difficulty walking. Discovering the areas of the brain that are activated when people with Parkinson’s experience shuffling, freezing in place or feeling off balance. If Hinton identifies the brain networks that are affected, her work could help researchers harness future therapies to correct people’s gait.

Olivier Kerdiles, a doctoral student at Université Laval, is exploring the possibility that diet and exercise could prevent the onset of Parkinson’s disease as well as reduce the loss of neurons and even reverse other negative effects. He is studying omega-3, a group of fatty acids known to be beneficial to our metabolism, which might also contribute to the health of neurons by maintaining their ability to produce the vital agent dopamine, which transmits signals from the brain to the body.

Research into the process that kills the brain cells that generate dopamine, the chemical that is essential to healthy movement, has zeroed in on a protein called alpha-synuclein. At Laval University, Professor Martin Levesque studies the connection between alpha-synuclein and another protein called Rin. If he can determine a way to use Rin to regulate and reduce the amount of alpha-synuclein accumulating in brain cells, researchers could halt or slow the progression of Parkinson’s disease.

Stopping driving is a major blow to the independence of people with Parkinson’s disease. At Western University, Professors Liliana Alvarez and Jeffrey Holmes test the effectiveness of car warning systems that beep or flash flights if a car is in the driver’s blind spot when they switch lanes. If they confirm this existing technology could help people with Parkinson’s, or can modify the lane-changing aids to be more effective, the recommendations would help people keep driving and stay independent longer.