New drug may reverse memory loss in Alzheimer's

In a breakthrough, researchers have developed the first experimental drug to boost brain synapses lost in Alzheimer's disease, which may reverse memory loss.
The drug created by researchers at Sanford-Burnham Medical Research Institute, called NitroMemantine, combines two FDA-approved medicines to stop the destructive cascade of changes in the brain that destroys the connections between neurons, leading to memory loss and cognitive decline.
The decade-long study, led by Stuart A Lipton, professor and director of the Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, shows that NitroMemantine can restore synapses, representing the connections between nerve cells (neurons) that have been lost during the progression of Alzheimer's in the brain, medicalxpress.Com reported.

The focus on a downstream target to treat Alzheimer's, rather than on amyloid beta plaques and neurofibrillary tangles - approaches which have shown little success - "is very exciting because everyone is now looking for an earlier treatment of the disease," Lipton said.
"These findings actually mean that you might be able to intercede not only early but also a bit later," said Lipton.
And that means that an Alzheimer's patient may be able to have synaptic connections restored even with plaques and tangles already in his or her brain.

In their study, conducted in animal models as well as brain cells derived from human stem cells, Lipton and his team mapped the pathway that leads to synaptic damage in Alzheimer's.

They found that amyloid beta peptides, which were once thought to injure synapses directly, actually induce the release of excessive amounts of the neurotransmitter glutamate from brain cells called astrocytes that are located adjacent to the nerve cells.
Normal levels of glutamate promote memory and learning, but excessive levels are harmful. In patients suffering from Alzheimer's disease, excessive glutamate activates extrasynaptic receptors, designated eNMDA receptors (NMDA stands for N-methyl-D-aspartate), which get hyperactivated and in turn lead to synaptic loss.
By shutting down hyperactive eNMDA receptors on diseased neurons, NitroMemantine restores synapses between those neurons, researchers said.
The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).