Scottish research identifies potential pathway for treating neurodegenerative diseases such as Alzheimer’s

Researchers at the University of Glasgow recently published a paper in which they identified a molecular pathway as a potential target for treating neurodegenerative disease like Alzheimer’s disease (AD). By activating a type of receptor in a mouse model of these diseases, they were able to not only treat symptoms but also slow disease progression and prolong survival.

The target - the M1 receptor

The therapeutic target at the centre of the work by Dwomoh and colleagues is the M1 receptor. This is a type of acetylcholine muscarinic receptor in the brain, especially expressed in the hippocampus and cortex. For this reason, it is speculated that this receptor could play a role in restoring cognitive functioning. Beyond this, research has shown that it may have a neuroprotective effect in neurodegenerative disorders. In order to assure that the treatment would only target this subtype and not any of the other four muscarinic receptor subtypes, the researchers used a tool called positive allosteric modulators (PAMs), known to be highly selective for the M1 receptor. Using these methods in an animal model for neurodegenerative disorders, the authors were able to significantly reduce markers of neurodegeneration and neuroinflammation in mice , as well as prolong their survival and improvement of behavioural symptoms.

Need for treatment of illness beyond symptom control

Currently, there is a big need for therapeutic strategies that stop or slow down the progression of neurodegenerative diseases such as AD and Parkinson’s disease. Just a few weeks ago, the drug lecanemab made headlines since it has shown to have a small effect on the disease progression of AD at early stages, yet the scale of its impact on AD patients debated. One of the lead researchers of the study by Dwomoh and colleagues, Professor Craig Lindsley from the Department of Pharmacology at Vanderbilt University is hopeful that their work could contribute to finding ways to slow down disease progression: “we genuinely have the prospect of not only treating the symptoms of Alzheimer’s disease, including memory loss, but that we might actually be able to slow the disease and increase the lifespan of sufferers from neurodegenerative diseases like Alzheimer’s disease.” Despite the substantial overlap between the study’s mouse model and Alzheimer’s disease, it is not a given that the results are translatable to humans. Before considering the potential advancements in clinical interventions this work could lead to, its findings need to be tested in human clinical populations.