Pure chance brought Dr. Shaun Sanders and Dr. Melanie Alpaugh into the same space at the University of Guelph. The professors in the Department of Molecular and Cellular Biology were assigned to share lab space in the Summerlee Science Complex before they learned their research interests overlapped.
"It was really serendipitous," Sanders says. "I couldn't be happier, sharing a space with Alpaugh."
The pair has teamed up to research Huntington's disease, an incurable, inherited brain disorder that causes cells in parts of the brain to die. As cell death progresses, people living with the disease become less able to recall events, make decisions and control emotions and movements. While everyone has the huntingtin protein, people with the disease have a mutated version of the protein that causes cells in the brain to die.
Both Sanders and Alpaugh were drawn to Huntington's disease research in graduate school and are pleased to continue their research at U of G.
"It's a really devastating disorder. I've had the privilege of meeting patients with Huntington's disease and giving them lab tours, and it just means so much to them," Sanders says. "This really motivates me to do this research."
Drs. Shaun Sanders and Melanie Alpaugh in their lab in the Summerlee Science Complex
Researching key enzyme
Thanks to funding from the Huntington Society of Canada, Sanders and Alpaugh will spend the next two years researching whether inhibiting a key enzyme in the brain called dual leucine zipper kinase (DLK) could be a new therapeutic treatment for Huntington patients. These studies will be performed in collaboration with Dr. Dale Martin at the University of Waterloo.
DLK tells brain neurons to die in patients with brain and spinal cord injuries and other types of neurodegeneration and the U of G team will investigate if inhibiting DLK could help slow Huntington's disease.
"There's a lot of interest for DLK in injury and other neurodegenerative disorders like ALS and Alzheimer's, but nobody has explored it in Huntington's disease at all," Sanders says.
Their research will look at whether steps aimed at reducing DLK in cultured mouse and patient-derived neurons can prevent further cell death and mitigate the symptoms of the disease.
"This will allow us to study and learn things applicable to Huntington's and other disorders," Alpaugh says. "There are lessons here that can be applied to a broader community as well."
Laying groundwork for a cure
The work to develop new treatments is a long one. On average, it takes about 12 years of testing and development to bring a new medication to market and into doctors' hands. Much of the groundwork for those therapies begins in the discovery phase in labs like Sanders' and Alpaugh's.
The neuroscientists use the latest genetic, biochemical, and cell biology approaches to understand the proteins involved in the brain that cause the disease and identify potential ways to target these proteins.
"We need to do these types of cell biology and biochemistry first to lay the groundwork for future treatment," Alpaugh says.
Moving forward with molecular research requires extensive collaboration, which can be done right here at U of G.
"We have a lot of faculty members across departments and colleges thinking outside the box and researching things in new and exciting ways," Sanders says. "There's a lot of opportunities here for unique collaborations." Sanders adds that the location of U of G within the research environment of southern Ontario allows for the formation of networks amongst institutions, such as this research partnership with Martin.
If this research validates DLK as a possible therapeutic target for Huntington's disease, the pair says the next step is moving into small and large animal trials and then even perhaps human clinical trials down the line.
"We want to know if this could potentially be a disease-modifying therapy," Alpaugh says. "That's a big statement, but we have to start here to get there."
This research is being conducted in partnership with Dr. Dale Martin from the University of Waterloo with support from the Huntington Society of Canada.
