Gladstone researchers, in collaboration with Genentech, a member of the Roche group, have shown therapeutic efficacy of a new experimental drug in mouse models of Alzheimer’s disease and a rare genetic form of epilepsy known as Dravet syndrome. The small molecule increases the activity of a subset of neurotransmitter (NMDA) receptors that are found at synapses, the connection points between neurons. These receptors are known to support cognition and memory by enhancing communication between neurons. The new research shows that enhancing the activity of synaptic NMDA receptors helps restore the brain’s rhythms to normal patterns, and improves memory.
“Before now, we haven’t had ideal tools to enhance synaptic NMDA receptors,” said Gladstone Associate Investigator Jorge Palop, Ph.D., senior author of the study, which was published in the journal Cell Reports. “Now, the ability to specifically target these receptors opens up a lot of new possibilities for treating cognitive disorders.”
“This is the first time we’ve explored what this type of experimental drug does in animal models,” said Jesse Hanson, a scientist at Genentech and lead author of the new paper. “It was very gratifying to see an effect on both the brain’s electrical activity and the animals’ behavior.”
Abnormal activity of NMDA receptors has been long implicated in neuropsychiatric, epileptic, and neurodegenerative disorders. But previous compounds for altering NMDA receptor function worked by binding to all subtypes of NMDA receptors, and either completely blocked the receptors or put them in a permanently active state. Researchers have theorized that modulating the receptors only at active synapses may help diverse cognitive diseases by potentiating synaptic function and increasing neuronal communication.