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Groundbreaking drug discovery could lead to new Alzheimer’s treatments

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Scientists have made a breakthrough discovery that could advance the treatment of Alzheimer’s Disease.

Researchers from the University of Glasgow and the biotechnology company Sosei-Heptares Ltd, have designed a new molecule that selectively targets a specific receptor protein in the brain.

Professor Andrew Tobin, professor of molecular pharmacology at the University of Glasgow, said the molecule has the potential to create new drugs that could improve cognitive function in Alzheimer’s patients by activating memory and cognitive centres within the brain.

“This is a true bench-to-bedside discovery, many years in the making.

“We are thrilled that this hugely important and global collaboration with our partners at Sosei Heptares and others has resulted in a highly sophisticated drug design approach that offers huge potential to improve the treatment of Alzheimer’s Disease, by activating memory and cognitive centres within the brain.

“We are extremely encouraged by our findings so far and are very hopeful that this could lead to new treatment options for patients with this devastating disease.”

There are currently no drugs that can stop or slow the progression of Alzheimer’s Disease. However, there are some that work to recover memory loss and improve cognitive function in early dementia.

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 (M1 receptor) in the brain, which is known to play a central role in memory and cognition.

Subsequent studies tested the hypothesis that these molecules will retain cognitive benefits and without dose-limiting side effects.

The research team used detailed knowledge of the M1 receptor’s 3D structure to design a selective modulator.  And subsequent pre-clinical studies confirmed the designed molecule retained its memory-improving properties while minimising side effects associated with previous attempts to target the M1 receptor.

Finally, clinical studies demonstrated that the M1-selective clinical candidate HTL9936, at meaningful doses in healthy volunteers, showed fewer reduced side effects than traditional drugs.

These groundbreaking results prove the hypothesis and that new approaches using 3D structures of receptors can be applied to the M1 receptor to create a potential new medicine for Alzheimer’s Disease patients.

The approach has since been used to design other new molecules that are able to treat the symptoms of Alzheimer’s Disease and other dementias.

Dr James Connell, head of translational science at Alzheimer’s Research UK, welcomed the discovery but warned that the drug candidate needs to be tested in people with Alzheimer’s disease to see if it delivers any benefit.

“People with dementia need treatments that can help with their symptoms including problems in learning and memory.

“While existing symptomatic drugs can make a difference to people’s lives, they have limited clinical benefit and patients often experience adverse side effects.

“Investigating and designing new approaches to alleviate symptoms of memory loss is necessary for people with dementia.

“Over the years, the receptor this drug targets has been the subject of intensive research, and it is promising to see that new technology has the potential to design new drugs that can selectively activate this target. These studies have shown positive results in lab-based studies and in older healthy adults.

“It’s encouraging to see pharmaceutical companies working in partnership with researchers based in universities to conduct meaningful and relevant drug discovery.

“While these early findings seem encouraging for this drug target, the drug candidate needs to be tested extensively in people with Alzheimer’s disease to see if it delivers any benefit.”

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