New Alzheimer's Drug Boosts Lost Brain Synapses: NitroMemantine Works in Hours

First Posted: Jun 18, 2013 10:38 AM EDT

There's a new drug out there that may help Alzheimer's patients in the near future. An experimental drug, called NitroMemantine, boosts brain synapses lost in Alzheimer's disease. Combining two FDA-approved medicines, this new drug can halt the destructive cascades in the brain that destroy the connections between neurons.

Scientists actually conducted studies in animal models as well as brain cells derived from human stem cells in order to better examine Alzheimer's. More specifically, they 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 excess amounts of the neurotransmitter glutamate from brain cells. In patients suffering from the disease, excessive glutamate activates receptors, called eNMDA receptors, which are then hyperactivated and, in turn, lead to synaptic loss.

The researchers had previously discovered another drug, called memantine, which could be targeted to eNMDA receptors to slow the hyperactivity seen in Alzheimer's. Yet memantine's effectiveness has been limited, mainly because the medicine is a positively charged molecule. This positive charge is repelled by a similar charge inside diseased neurons, which means that memantine is repelled from its intended eNMDA receptor target.

In order to overcome this issue, the scientists found that a fragment of the molecule nitroglycerin, another FDA-approved drug used to treat episodes of chest pain, could bind to another site. The researchers combined the two drugs, connecting this fragment of nitroglycerin to memantine, in order to create a new, dual-function drug.

"We show in this paper that memantine's ability to protect synapses is limited," said Stuart Lipton, one of the researchers, in a news release. "But NitroMemantine brings the number of synapses all the way back to normal within a few months of treatment in mouse models of Alzheimer's disease. In fact, the new drug really starts to work within hours."

This new drug could be a game changer when treating patients that have had Alzheimer's disease for some time. It shows that treatments can be given later rather than always earlier.

The findings are published in the journal Proceedings of the National Academy of Sciences.

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