From structure to clinic: Design of a M1 muscarinic acetylcholine receptor agonist with the potential for symptomatic treatment of Alzheimer’s disease
By Sosei Heptares | Nov 24, 2021
An extensive review in the prestigious journal Cell describes ground-breaking research – led by Sosei Heptares in collaboration with the University of Glasgow and others – that describes, for the first time, the process of designing a new molecule (HTL9936) to selectively target the muscarinic M1 receptor 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, while minimizing side-effects associated with previous attempts to target the M1 receptor.
The M1 receptor is a longstanding and important target for the alleviation of cognitive loss in Alzheimer’s disease patients, seeking to correct diminishing cholinergic transmission, although current therapies have shown limited effectiveness in clinical practice.
These exciting results substantiate the power of SBDD applied to the M1 receptor, an approach Sosei Heptares is using to create new molecules with superior properties for treating the symptoms of dementia and advancing them in preclinical development.
The research also has broader implications highlighting a powerful approach to address other GPCRs linked to a wide range of disease.
From structure to clinic: Design of a M1 muscarinic acetylcholine receptor agonist with the potential for symptomatic treatment of Alzheimer’s disease, By Brown, et al (2021) Cell.
This work was supported by The Wellcome Trust.