Dr. David Vocadlo is leading one of five BC researchers leading teams supported through the British Columbia Alzheimer’s Research Award. Established in 2013 by the Michael Smith Foundation for Health Research (MSFHR), Genome British Columbia (Genome BC), The Pacific Alzheimer Research Foundation (PARF) and Brain Canada, the goal of the $7.5 million fund is to discover the causes of and seek innovative treatments for Alzheimer’s disease and related dementias.
Alzheimer’s disease (AD) is a debilitating and progressive neurodegenerative disease, accounting for almost two-thirds of all dementias in Canada, and in BC affects up to 70,000 people. Symptoms include memory loss, behaviour and personality changes, and a decline in cognitive abilities.
Current AD medications treat symptoms of the disease, but none exist that can stop or even slow the progression of AD which starts in the brain many years before it manifests. The need for AD therapies that treat underlying progression of the disease is paramount for the aging population, in particular because of the projected increase in the number of AD patients.
Dr. David Vocadlo, a professor in Chemistry and Molecular Biology & Biochemistry and Canada Research Chair in Chemical Biology at Simon Fraser University (SFU), aims to address several key challenges that would clear the way for a promising new AD therapeutic target.
The two biological hallmarks of Alzheimer's disease in the brain, neurofibrillary tangles and amyloid plaques, are caused by the dysfunction and abnormal accumulation of specific proteins that can kill brain cells over time, progressively impairing brain function.
Vocadlo and a multidisciplinary group of research teams from SFU, the University of British Columbia (UBC) and the University of York in the UK, are pioneering their new approach that has been shown to block disease progression in animal models of AD by blocking the toxicity of the brain proteins that form the tangles within brains. Their approach centres on a specialized sugar unit called O-GlcNAc. Clumps of protein from AD brains have almost none of this sugar attached to them because the O-GlcNAcase enzyme continues to remove this sugar modification.
Vocadlo’s therapeutic goal is to use small molecules to block the activity of the O-GlcNAcase enzyme, and in this way increase the levels of O-GlcNAc in the brain to prevent this protein from clumping together and becoming toxic. Vocadlo’s team is currently advancing this therapeutic target in order to advance it into the clinic.