LA JOLLA — (Note: This article is an expanded version of my previous blog post. It includes comment from other Alzheimer's researchers to give context).
Brain cells harmed by Alzheimer’s disease can be repaired by a newly invented compound, according to a study led by Sanford-Burnham Medical Research Institute scientists. The compound, called NitroMemantine, is ready for human clinical trials, said Stuart A. Lipton, the Sanford-Burnham scientist who headed the study.
A study of the compound’s effectiveness in repairing synapses in mice was published Monday in the Proceedings of the National Academy of Sciences. Synapses transmit impulses from one neuron to another; their degeneration is characteristic of Alzheimer’s.
Artist's rendering of the loss of neuron synapses. — NIHLipton and colleagues created NitroMemantine by combining two existing drugs, nitroglycerin, used for angina; and memantine, which slows the progression of Alzheimer’s, but does not stop it. The combination makes the drug much more powerful, Lipton said. In studies of Alzheimer’s model mice, the drug produced synaptic repair.
Unlike most Alzheimer’s drugs that have been developed in recent years, NitroMemantine doesn’t inhibit formation of plaques of amyloid beta protein. Many scientists think that the plaques, or a altered form of another protein called tau, cause degeneration by forming insoluble clumps in neurons.
Lipton said focusing on synapses is a better target, 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 failed.
“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 questioners of the amyloid hypothesis from the Salk Institute have come up with their own compound that reverses symptoms of Alzheimer’s in mouse models. This compound, called J147, is derived from turmeric, a component of curry.
Dave Schubert, a Salk scientist who led the discovery of J147, gave a cautious endorsement of the NitroMemantine study.
“NitroMemantine is an interesting molecule based upon the FDA-approved Alzheimer’s disease drug memantine,” Schubert said. “It may have therapeutic potential, but the only way to determine this is to get it safety-tested and into the clinic.”
However, the advocates of amyloid beta and altered tau have their own research to point to. A new hypothesis says the interaction of both proteins causes Alzheimer’s. A paper making that case was published in the June edition of the Journal of Alzheimer’s Disease.
Examinations of Alzheimer’s mice and post-mortem human brain tissue from Alzheimer’s patients found that the neurons contained aggregations of both proteins, said Hemachandra Reddy, a researcher at Oregon Health & Science University who led the study. The aggregation was not found in control mice and humans who did not have Alzheimer’s.
“Currently, we are doing drug screening to see if any of those molecules can inhibit the interaction,” Reddy said.
Another researcher said some of the Alzheimer’s drugs that have failed to help patients may still be useful as prevention.
http://news.google.com/news/url?sa=t&fd=R&usg=AFQjCNHhOpbkMlrHw8S35PrV0u-1jCXl7A&url=http://www.utsandiego.com/news/2013/jun/19/alzheimers-nitromemantine-lipton/
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