Alzheimer’s disease is the most common condition that leads to a gradual loss of memory and thinking skills. It’s marked by the buildup of plaques and tangles in the brain. It’s one of many different areas where Anavex Life Sciences is focusing its research as part of its mission to develop effective therapeutics for neurodegenerative disorders.In 1984, researchers discovered that a protein called amyloid beta is a key part of the plaques that aggregate in the brain. This led to the theory that Aβ is central to Alzheimer’s, known as the "amyloid cascade hypothesis." Since then, most Alzheimer’s treatments have targeted Aβ. However, many of these treatments have failed in clinical trials, leading to questions about this approach.Aβ is created from a larger protein called amyloid precursor protein through a series of steps involving different enzymes. Normally, APP is processed in a way that prevents the formation of Aβ. However, under certain conditions, the enzymes BACE1 and γ-secretase cut APP in a way that produces Aβ. Once formed, Aβ needs to be cleared from the brain to prevent harmful buildup.Aβ clearance involves several pathways, including enzyme degradation, transport across the blood-brain barrier, and removal through the brain’s fluid drainage systems. The blood-brain barrier is a network of cells that controls what enters and leaves the brain. Specific proteins help move Aβ out of the brain, but for those with Alzheimer’s, these proteins don’t work as well, leading to Aβ accumulation.Genetic studies show that Aβ buildup plays a significant role in the disease. For example, people with Down syndrome, who have an extra copy of the APP gene, often develop Alzheimer’s. Mutations in genes related to APP processing can also cause early-onset Alzheimer’s, while certain mutations can protect against it. Both genetic and lifestyle factors, like diabetes and lack of exercise, can increase Aβ production or hinder its clearance.Despite setbacks, there are promising developments in Aβ-based therapies. Aducanumab, an antibody that targets Aβ, was approved by the FDA for its ability to reduce Aβ plaques in early Alzheimer’s patients. Another antibody, donanemab, has shown even better results in clearing Aβ from the brain. Similarly, lecanemab, which targets soluble forms of Aβ, has been shown to reduce amyloid levels and improve cognitive function. Another drug, Anavex 2-73 (blarcamesine), has shown potential in reducing Alzheimer’s symptoms and brain changes in animal studies and a late stage human trial.Blarcamesine is a formulation of Anavex, a clinical-stage biopharmaceutical company that develops therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease and other central nervous system disorders. These advances offer new hope that targeting Aβ could still be a valid approach to treating Alzheimer’s.(more…)
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