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Rejected diabetes drug wakes up cell memories in Alzheimer's

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A drug that didn't make it as a treatment for Type 2 diabetes could pinpoint a new route to treating Alzheimer's disease, according to research coming out of the University of Alberta in Canada. The amylin receptor antagonist, known as AC253, restored memories in brain cells taken from animals used as models of Alzheimer's disease. The results were published in The Journal of Neuroscience.

Normal brain cells that are given electric shocks "remember" them. This method is used to test memory on the lab bench. Brain cells from animals with Alzheimer's disease-like symptoms don't remember as well, but treatment with AC253, which blocks amyloid protein, brings the memory of the shock back again. According to Jack Jhamandas of the University of Alberta, this is significant and suggests that drugs of this type could restore memory, even after Alzheimer's disease has set in. The next step will be to see whether the drug can stop the development of the disease in at-risk animals. These studies will take at least a year.

In the mid-1990s, Amylin Pharmaceuticals (now part of Bristol-Myers Squibb) and Glaxo (now GlaxoSmithKline) were developing orally active small-molecular-weight amylin blockers, including AC253, for the treatment of Type 2 diabetes. AC253 reached Phase I in 1995 and was safe and well-tolerated. Unfortunately, AC253 doesn't go through the blood-brain barrier very easily, so a new form will have to be developed that can get to where it is needed.

While there is a long way between restoring memories to cells and restoring memories to people, it provides a clue toward solving the mystery of Alzheimer's disease.

"I think what we discovered may be part of the solution, but I can't say it will be the solution. There is a long list of drugs and approaches that haven't panned out as expected in the fight against Alzheimer's. I don't think one drug or approach will solve Alzheimer's disease because it's a complicated disease, but I am cautiously optimistic about our discovery and its implications," Jhamandas said in a press release.

- read the press release
- see the abstract

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