$3-million grant supports Tanz Centre research to advance Alzheimer’s drug to clinical trials
Paul Fraser, scientist at the University of Toronto’s Tanz Centre for Research in Neurodegenerative Diseases, has received a $3-million grant from the Weston Family Foundation to prepare a promising therapeutic for Alzheimer’s disease for clinical trials. The compound, SBT02, is an innovative approach to Alzheimer’s disease treatment that may help prevent and even reverse cognitive decline.
“There are really no Alzheimer’s drugs now that can prevent the brain damage or the neuronal activity that are lost in the disease. And the amazing thing is that this compound can work even in an advanced pathology state,” says Fraser, who is also the Jeno Diener Chair in Neurodegenerative Diseases and a professor in the department of medical biophysics at U of T’s Temerty Faculty of Medicine.
“This compound is quite a different way of approaching the disease. Other drugs are designed to break up the amyloid aggregates that accumulate in the brain, but this compound is meant to prevent further damage to the brain cells and even recover or repair some of the damage that’s been done.”
One of the hallmark features of Alzheimer’s disease is the clumps of misfolded amyloid-beta protein that form in the brain, which accumulate over years and damage neurons, eventually leading to dementia and cognitive decline. Research has typically focused on developing treatments to target these aggregations, including one drug approved in Canada last fall. These therapies can clear away the amyloid-beta clumps and slow progression of the disease, but they can’t undo the damage to brain cells that has already taken place.
Fraser’s research of amyloid beta and Alzheimer’s disease has taken a different approach. His team was one of the first groups to describe a protein called SUMO2 and its protective role in the brain. SUMO2 joins with other proteins to help protect synapses in the brain from damage, even when amyloid aggregates are present, but it is found in lower amounts in brains with Alzheimer’s disease compared to healthy brains.
Some years ago, Fraser’s team began developing the small molecule called SBT02 that also acts on proteins in neurons and restores SUMO2 activity, making neurons more resistant to the toxic effects of Alzheimer’s pathology. The team has been studying the compound and generating evidence to support its use as an Alzheimer’s therapy.
“We showed in our animal models that giving the compound after they have cognitive impairments could reverse some of the damage,” says Fraser. “It can’t bring nerve cells back to life, but it can repair the damage and dysfunction that’s already happened.”
Fraser previously received funding from the Weston Family Foundation to research the compound, specifically minimum dose required, potential toxicity and effectiveness.
Based on the success of that work, the new funding from the foundation will support Fraser and his team in completing some crucial steps that need to be undertaken to bring the compound to clinical trials. They will manufacture clinical grade SBT02 needed to complete investigational new drug studies, which are required by regulators before clinical trials are approved.
They will also study safety and toxicity of SBT02 in animal models, and study the target proteins and mechanisms of action to gain a better understanding of how the protein works. Together, the data from the studies will support an application for human clinical trials to begin in the next few years.
If successful, the compound could be paired with drugs that target the amyloid-beta aggregations, thus slowing progression of the disease and reversing the damage that has already occurred.
“As the field looks beyond amyloid-focused therapeutic approaches for Alzheimer’s disease, there is a growing recognition that patients will likely need additional, complementary treatments that are both safe and effective. Dr. Fraser’s previous work, supported by the Weston Family Foundation, showed that his novel SUMO-based therapeutic has the potential to both prevent, and even reverse, memory loss in Alzheimer’s disease models,” says Christian Bauta, Chair of the Weston Family Foundation.
“By continuing to support this work through the Follow-on Funding program, our goal is to help advance this promising early-stage innovation into the next phase of development, bringing it closer to real-world use. We believe this work could open the door to new therapeutic strategies that preserve brain function and slow memory decline in people living with Alzheimer’s disease.”
Graham Collingridge, director of the Tanz Centre, says that targeting SUMO2 activity is an exciting and novel approach. “Paul's work exemplifies how the Tanz Centre translates discoveries of the basic biology of neurodegenerative diseases into potential new treatments for these debilitating conditions. Having fundamental researchers and clinicians collaborating under one roof is the key to its success.”
Fraser’s team first published research on the SUMO protein about 20 years ago, and he says that seeing the research advance to point of being near clinical trials — with support along the way from the Weston Family Foundation — has been highly motivating.
“I started this work with just one grad student, and then we connected with collaborators in the U.S. and Italy. It’s been gratifying to see this research advance, and to actually turn into a drug that could benefit people is extraordinary,” says Fraser.
“Support of the Weston Family Foundation has been essential to do the preclinical testing and prove that this compound works,” Fraser adds. “To be supported again is a big confidence boost on the potential this therapy has for patients suffering from Alzheimer’s disease.”
