Bench-to-bedside drug design could lead to new Alzheimer’s Disease treatments
An international team of scientists and pharmaceutical collaborators have made a breakthrough 'bench to bedside' discovery, ten years in the making, which they hope will advance the future treatment of Alzheimer's Disease in patients. The research - conducted at the University of Glasgow and the biotechnology company Sosei-Heptares Ltd - and published in Cell describes, for the first time, the process of designing a new molecule to selectively target a specific receptor protein in the brain and demonstrating, through laboratory preclinical and human clinical studies, the potential of this approach to create superior new drugs to improve cognitive function in Alzheimer's Disease patients. There are currently no drugs that can stop or slow the progression of Alzheimer's Disease. However, there are drugs that work to recover memory loss and improve cognitive function in early dementia, but these drugs are often not very effective, and are associated with side effects that may limit their effectiveness in clinical practice. The study was focused on new molecules, designed by Sosei Heptares, that selectively target a protein called the M1 muscarinic acetylcholine receptor (or M1 receptor, a G protein-coupled receptor or GPCR) in the brain, which is known to play a central role in memory and cognition. Subsequent translational medicine studies tested the hypothesis that such molecules will retain cognitive benefits and lack dose-limiting side effects. Working closely together, the research team demonstrated that an exquisitely selective modulator could be successfully designed using detailed knowledge of the M1 receptor's 3D structure, despite its very close similarity to other types of muscarinic receptor.
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