Rosiglitazone, a diabetes drug initially developed by GlaxoSmithKline ($GSK) under the name Avandia, may have a second life as an Alzheimer's drug after all. After previous attempts elsewhere, researchers at the University of Texas Medical Branch at Galveston say that the treatment appeared to improve memory in preclinical testing, and they have a theory as to why.
What's more, the team says they and others are ready to begin clinical trials that test similar drugs targeted against insulin resistance as a treatment for early-stage Alzheimer's in people. Details of the research are published in The Journal of Neuroscience.
For the study, the Galveston team targeted a molecule known as ERK. In Alzheimer's patients' brains, ERK runs wild and messes up neuronal signaling, affecting memory and the ability to learn. In genetically engineered mice with the equivalent of mild cognitive impairment in human Alzheimer's, the same thing happens. In tests involving the special mice, the drug appeared to work, improving learning and memory. (And as rosiglitazone also treats diabetes, the drug additionally stabilized their insulin resistance.) How did it work? The researchers believe that it helped neutralize Alzheimer's effects by activating the PPARγ pathway, which works, in part, with genes that respond to ERK.
This research represents a major milestone. But we have to couch this by noting that the treatment may not have the same results in people, and previous tests of rosiglitazone didn't show that it improved cognition. That said, hitting Alzheimer's patients at an earlier stage of their disease could generate better results.
There may also be concern about safety if the research moves ahead. Regulators in Europe pulled Avandia a few years back as a diabetes treatment, and the FDA restricted its use because of worries that it could harm cardiovascular function. Assuming the drug does generate Alzheimer's benefits down the line, regulators will likely wonder: Do the benefits outweigh any risks?
- read the release
- here's the journal abstract
Special Report: The Alzheimer's pipeline: What's next?