Advertise With UsAdvertise on our extensive network of industry websites and newsletters.
Get the PBR newsletterSign up to our free email to get all the latest PBR
news.EnVivo Pharma has discovered that EVP-6124, its alpha-7 nicotinic acetylcholine receptor agonist, possesses a new mechanism of acting as a co-agonist with Acetylcholine (ACh) to enhance cognition.
Subscribe to our email newsletter
EnVivo claimed that, by acting as a co-agonist and sensitising the alpha-7 receptor, EVP-6124 makes it possible for smaller amounts of naturally occurring ACh, typically found in individuals with memory disorders such as Alzheimer’s, to be required to activate the receptor.
EnVivo’s research showed that memory deficits can be minimised or entirely reversed by controlling the neuronal channel with EVP-6124 alone or in combination with other Alzheimer’s drugs.
EnVivo president and CEO Kees Been said that it was a groundbreaking research in terms of understanding how the alpha-7 receptor operates in conjunction with EVP-6124.
EnVivo simulated physiologically relevant brain conditions in-vitro and alpha-7 receptor action was measured in response to ACh in the presence of low EVP-6124 concentrations.
At drug concentrations resulting in pro-cognitive effects in in-vivo studies, EVP-6124 appeared to increase the alpha-7 receptor response to Ach.
EnVivo said that this suggests that at low concentrations, EVP-6124 acts as a co-agonist and sensitises the alpha-7 receptor to its natural response to ACh, but does not desensitise the receptor.
This co-agonist mechanism of action was supported by testing the combined effect of sub-threshold doses of both EVP-6124 and Donepezil (Aricept) on the memory deficit in a rat model.
EnVivo stated that while each drug alone at these very low doses had no effect on reversing the deficit, dosing the two agents together completely restored the memory function in these animals.
Cleveland Clinic Lou Ruvo Center for Brain Health director Jeff Cummings said that low doses of EVP-6124 could enhance current cholinergic treatments and when combined with available agents could provide a pro-cognitive effect for as long as acetylcholine is present in the brain.
"EnVivo’s experimental results suggest that pro-cognitive drugs could be taken in earlier stages of Alzheimer’s disease and that EVP-6124 could continue to boost the pro-cognitive effect of cholinesterase inhibitors throughout the disease course," Cummings said.
"The effectiveness of reduced doses of cholinesterase inhibitors when given with EVP-6124 in experimental models suggests that EVP-6124 might allow use of lower doses with fewer side effects in humans."