A University of Winnipeg professor is hoping to make an important breakthrough in amyotrophic lateral sclerosis (ALS) treatment.
Dr. Renée Douville, Department of Biology, and collaborators Dr. Jody Haigh, University of Manitoba, and Dr. Domenico Di Curzio, St. Boniface Hospital Albrechtsen Research Centre, received a $125,000 Discovery Grant from the ALS Society of Canada and Brain Canada in March for their research project: DNA Damage Driven Motor Disturbance in ALS: An ERVK Integrase Transgenic Mouse Model.
“The Discovery Grant program continues to support critical Canadian research that contributes to the global effort on understanding and treating ALS,” said Dr. David Taylor, Vice-President, Research and Strategic Partnerships, ALS Canada. “Over the past 15 years, many discoveries made with these funds have provided a foundation for studies that are impacting humans today, whether through clinical trials or critical initiatives like CAPTURE ALS.”
The Discovery Grant program supports projects that are focused on identifying causes of ALS, treatments for ALS or related neurological diseases, and avenues to maximize function, minimize disability, and optimize quality of life for persons and families living with ALS. The nine projects receiving funding were selected following a competitive peer-review process, in which international ALS experts considered the merit of the applicant, the quality of the project, and the potential to advance the field of ALS research.
“I want to thank The University of Winnipeg, St. Boniface Albrechtsen Hospital Research Centre, ALS Canada, and Brain Canada for all of their support and giving our lab a chance to develop this research,” said Dr. Douville. “We’re really excited about the prospect of bringing new therapeutics to patients with ALS.”
Dr. Douville’s research
Unlike most ALS researchers, Dr. Douville and her team of researchers study ALS from a viral perspective. More specifically, they study endogenous retroviruses, which is a dormant group of viruses that make up eight per cent of human DNA.
“In some cases, the viruses become reactivated in the neurons of patients with ALS,” Dr. Douville explained. “We’re trying to figure out how expression of these endogenous retroviruses might cause or contribute to ALS neuropathology.”
Previous to this announcement, Dr. Douville and Dr. Alberto Civetta, Department of Biology, received funding from the ALS Association in the United States for similar research. Dr. Douville and Dr. Civetta, who is an expert on fruit flies, designed endogenous retrovirus-K (ERVK) transgenic fruit flies that allowed them to study the viral protein integrase.
“By using this fruit fly model, we were able to establish that the DNA damage caused by the viral protein actually led to motor disturbances in the fruit fly,” Dr. Douville noted. “When we treated the fruit fly with integrase inhibitors, which are antiviral drugs, we reversed the motor deficiencies that we saw.”
They also discovered a sex-specific difference in the treatment, as some antiviral drugs worked better in female flies and some of the antiviral drugs worked better in male flies. This suggests the antiviral drugs may work differently in different patients.
With two years of funding secured, Dr. Douville is collaborating with Dr. Haigh to transition the current fruit fly model system to an ERVK integrase mouse model system.
“We just recently had little mouse pups that were born and they’re chimeric. They express some cells from one mouse line and some mouse cells that can express the ERVK integrase protein,” she explained. “With these mice, we’re going to be able to set up a similar system to be able to test for how ERVK integrase affects the brain, movement, and neuroinflammation.”
The mice will be housed at St. Boniface Albrechtsen Research Centre in a vivarium. The team is also setting up a behavioural suite to be able to analyze mouse movement.
The ALS Society of Canada and Brain Canada Discovery Grant will also fund the salary of senior research fellow Dr. Di Curzio, who will be doing all the neuropathology on the mouse brains.
“From cells, to patient samples, to flies, and now mouse models, we have followed a research path that is highlighting how the activity of a single viral protein from ERVK can contribute to brain inflammation, neuronal death, and motor disturbances,” said Dr. Douville. “Our ultimate goal will be to evaluate if repurposing antiviral drugs could be a valuable therapeutic strategy. It has been an exciting journey and one we hope is effective for patients with ALS.”
News source: University of Winnipeg