LA JOLLA — A potential Alzheimer's drug actually restores synapses destroyed by the disease, says a Sanford-Burnham Medical Research Institute scientist who led development of the compound.
A study of the drug's effectiveness in mice was published Monday in the Proceedings of the National Academy of Sciences. (The study itself is available here).
Stuart A. Lipton, a researcher at Sanford-Burnham Medical Research Institute, studies Alzheimer's and other neurodegenerative diseases. — Sanford-Burnham Medical Research Institute
The compound is ready for human clinical trials, said Stuart A. Lipton, the Sanford-Burnham researcher leading the study. Instead of focusing on the amyloid beta pathway, which has resulted in repeated flops in drug development, the compound, called NitroMemantine, works on a downstream target.
Lipton and colleagues created NitroMemantine combining two existing drugs, nitroglycerin, used for angina; and memantine, sold under the brand name Namenda, which slows the progression of Alzheimer's.
Adding a portion of the nitroglycerin molecule to memantine boosts its effectiveness, Lipton said. In studies of Alzheimer's model mice, the drug produced synaptic repair. That's critical, he said, because the condition of the synapses correlates with cognitive function, and the presence or absence of amyloid beta plaques does not. Attempts to develop drugs on that hypothesis have crashed in a string of failures.
"All the big pharmas have lost sight of that," Lipton said. "They're so focused on amyloid beta or tau. They've even developed neuro-theological terms for themselves. They call the people the people working on amyloid beta 'baptists,' and people working on tau 'tauists.' It's almost become a religion, and yet those drugs have just been failing."
Other dissenters from the Salk Institute have come up with their own compound that reverses symptoms of Alzheimer's in mouse models. This compound is derived from turmeric, a component of curry.
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