Grant: Project Grant

People with Alzheimer's disease have difficulties to learn and retain information. Toxic products are known to damage brain cells and prevent their function. New memories can no longer be formed, and old memories are lost. Alzheimer's disease is devastating, daily. This is particularly true for patients who live with an early-onset type, which is inherited through known genetic mutations and can impact people as young as 30. The efficacy of promising therapeutics is compromised because they cannot enter the brain. We propose to deliver genes to brain cells and make them capable of producing their own therapeutics. This is called gene therapy and will provide cells the ability to protect themselves against degeneration. Briefly, genes encoding for therapeutics are placed in carriers. Then, these carriers are injected in the blood, and they enter brain cells. These cells can now produce their own therapeutics to counter toxic molecules for years to come. This approach is refined with a technology pioneered by researchers at Sunnybrook called focused ultrasound which is guided by magnetic resonance imaging (MRI). MRI-guided focused ultrasound does not require any surgical procedure. Parts of the brain affected by disease are targeted by MRI. Then, focused ultrasound is used to facilitate the entry of gene carriers within the brain regions of interest. This research will be done in animal models of Alzheimer's disease. We propose that gene therapy will protect the brain against damage and loss of function. Our long-term goal is to treat and improve the quality of life of people with Alzheimer's disease. In 2018, the first clinical trial testing safety of MRI-guided focused ultrasound in patients with Alzheimer's was completed at Sunnybrook. Gene therapy combined with MRI-guided focused ultrasound is well-poised to offer non-invasive and lasting therapeutics in the fight against Alzheimer's disease, particularly those with heredity early-onset Alzheimer's disease.