Sneaking therapeutics into the brain

There is no disease modifying molecule for Alzheimer’s disease currently on the market or in use. This is one the largest unmet medical needs in neuroscience. If no cure has be found by 2038, the total cost of care is expected to rise to $153 billion in Canada alone. Delivering drugs to targets in the brain is significantly impeded by a special protective layer, called the blood-brain barrier, which is designed to prevent toxins and anything potentially harmful from reaching the brain, but also prevents potentially lifesaving drugs from reaching the brain.

Nathan Yoganathan and his team are working on a way to solve this problem. Their goal is to take a disease-modifying molecule for Alzheimer’s disease that binds toxic amyloid proteins and sneak it across the blood-brain barrier by attaching it to another molecule that is able to cross. This is known as the Trojan horse method, and if the team is successful, it would represent the first time this has been achieved in humans. The project involves a collaboration between academia, non-profits, and small and medium-sized enterprises. The multidisciplinary, multi-institutional team from across the country is testing the efficacy of an Alzheimer’s disease modifying molecule from Kalgene coupled with a carrier molecule, both of which were developed by the National Research Council and licensed to Kalgene. The Montreal Neurological Institute and CIMTEC are also involved and their imaging and diagnostic expertise will measure if the conjugated molecule was able to cross the blood-brain barrier in humans and also effectively bind to toxic amyloid.

The objectives of the project are twofold: To successfully demonstrate that this Trojan horse method, proven in preclinical models, will also work to deliver the peptide to the human brain, and that the medicine is safe in Phase 1 clinical trials. Both of these objectives have already been accomplished in preclinical studies, which also demonstrated the efficacy of the peptide in clearing amyloid beta. The team has already made significant progress. In close collaboration with Kalgene, the Translational Neuroimaging Laboratory (McGill Research Centre for Studies in Aging, McGill University) demonstrated blood-brain barrier permeability, target engagement and drug efficacy in vivo using imaging methods in transgenic models. These exciting results will be announced at the Alzheimer’s Association International Conference, to be held in London in July 2017. In early 2018, KalGene will be initiating the first human clinical trial which will be led by Pedro Rosa-Neto, Serge Gauthier and Angela Genge from McGill University. Additionally, this project allows for the training of a large number of highly qualified professionals in the areas of advanced drug development and clinical trials.

If the team can successfully demonstrate safely delivering this Alzheimer’s disease modifying drug to the brain, this can also accelerate the development of therapies for other brain conditions.

“This grant was a catalyst to bring Canadian academics, clinicians, and companies together to use Canadian assets and Canadian intellectual property and Canadian expertise at every level, including the clinicians, to advance the project.”

— Nathan Yoganathan, Ph.D., CEO, Kalgene Pharmaceuticals