More than 20 years after the discovery of the parkin gene, linked to young onset Parkinson’s disease, researchers at the Ottawa Hospital and the University of Ottawa may have figured out how the gene protects the brain.
The study was led by the Schlossmacher team at the Ottawa Hospital Research Institute. Dr. Michael Schlossmacher, neurologist, Director of Neuroscience at The Ottawa Hospital and holder of the Bhargava Family Research Chair in Neurodegeneration at The Ottawa Hospital and his team have been working with this protein for more than 10 years. The results were recently published in the peer-reviewed journal Acta Neuropathologica.
The research team used human and mouse brain samples and engineered cells to find that the parkin protein works in two ways. First, it acts like a powerful antioxidant that disarms potentially harmful oxidants in the brain, including dopamine radicals. Second, as the brain ages and dopamine radicals continue to build up, parkin moves these harmful molecules to a special storage site within vulnerable nerve cells. There, they can continue to function normally throughout our lifespan.
Dr. Schlossmacher’s team knew that this protein protected us but they have found an important connection relating to young people who develop a certain type of Parkinson’s: People with mutations in both copies of the parkin gene are missing these protective effects. As a result, Parkinson’s develops before the age of 40. Those that develop symptoms for this specific reason (about 3 – 4 percent of all people diagnosed with Parkinson’s) typically see their disease manifest as a slow-moving form of Parkinson’s that impacts mostly motor symptoms. This is different from other people with Parkinson’s, who would otherwise also experience non-motor symptoms. Essentially, it looks like typical Parkinson’s but involves the loss of dopamine only, which is different from other pathologies. While researchers have long thought that parkin has a neuroprotective role in the brain, the exact mechanism was unclear. Many believed parkin’s role, as it relates to Parkinson’s disease, was to clear damaged mitochondria from the cell. The novel work by Dr. Schlossmacher’s team suggests it is actually the antioxidant function of the parkin protein that is essential for dopamine cell survival.
If confirmed, the results could point the way towards the development of new treatments that could deliver antioxidants. “If we could deliver antioxidants or a healthy copy of the parkin gene into the brains of people with these mutations, this could help slow down or even halt early-onset Parkinson’s,” said co-corresponding author and scientific project manager Dr. Julianna Tomlinson.
“What we don’t know yet is whether such an approach could also benefit individuals with late-onset Parkinson’s that is not linked to the parkin gene,” added co-corresponding author Dr. Schlossmacher. “We are eager to investigate this.”
He further notes that stratification or sub-typing of Parkinson’s is a major focus – and challenge – for people trying to understand and treat the disease. As we begin to learn more about the different causes of Parkinson’s and potentially different types of the disease, researchers will be better prepared to develop personalized treatments for people with Parkinson’s. More than that, these distinctions can also be used to develop better trials for medications.
Antioxidants, for example, have long been thought to play a protective role in Parkinson’s. But studies have not been able to prove a link between taking them and improving outcomes so far. It may be that people who carry this specific mutation would be good candidates for a future study using antioxidants to test their viability for this subtype only. Drs. Schlossmacher, Tomlinson and John Pezacki of the Department of Chemistry at uOttawa were recently awarded a new project grant from the Canadian Institutes of Health Research to continue this work.
A major challenge for being able to do studies on a subtype of Parkinson’s however, is the need for very large numbers of study participants to identify those subtypes in the first place. One of the goals of the Canadian Open Parkinson Network (C-OPN) is to build a large national list of people that are interested in getting involved in Parkinson’s research so that these types of stratification studies can be facilitated. C-OPN collects different types of information (e.g., clinical, lifestyle or genetic) on its participants so that specific subtypes of Parkinson’s can be identified and used to support further analysis to develop a better understanding of the disease. The hope is that centralizing information across Canada will lead to personalized treatments and ultimately a cure in the future.
That’s why Dr. Schlossmacher and his peers (notably Dr. David Grimes) at eight leading research institutes in Canada have come together as the first sites on board in C-OPN. To make meaningful discoveries, they need your help. C-OPN is a true collaboration between people living with Parkinson’s and the research community – your involvement is critical to helping the Canadian Open Parkinson Network reach its goals. The Ottawa site is one of several that are actively recruiting participants.