Grant: Project Grant

In the brain of people with Alzheimer's disease, toxic molecules are produced, leading to cellular and functional deficits, compromising the ability to learn and remember. Gradually, new memories can no longer be formed, and old memories are lost, causing devastating consequences on daily living. The efficacy of many promising therapeutics for Alzheimer's patients is limited by their poor ability to travel from the blood, where they are administered, to the brain, where they are needed. We propose to deliver genes which will integrate into brain cells and make them capable of producing molecules neutralizing toxic products related to the pathology of Alzheimer's disease. Genetic engineering of brain cells can provide self-defence mechanisms to fight Alzheimer's disease. Briefly, genes encoding for therapeutic antibodies are placed in gene carriers. Then, these gene carriers are injected in the blood and they enter the brain to modify cells affected by the disease, namely neuronal and vascular cells. Genetically modified cells gain the capability to produce therapeutics for years to come to alter the course of the disease. This approach is refined with a technology pioneered by researchers at Sunnybrook, coupling magnetic resonance imaging (MRI) and focused ultrasound. MRI-guided focused ultrasound does not require surgical procedure. Using MRI, parts of the brain that are burdened with the disease are localized and targeted with the ultrasound to facilitate the entry of gene carriers. This research will be done in animal models of Alzheimer's disease. We aim to provide a proof-of-concept at a preclinical stage, with the long-term goal to treat and improve the quality of life for people living with Alzheimer's disease. In 2018, the first MRI-guided focused ultrasound clinical trial in Alzheimer's patients was completed at Sunnybrook. Combined with ultrasound, gene therapy bodes well to provide brain cells the therapeutics they need to fight Alzheimer's disease.