November 21, 2012
Controversial Diabetes Drug Benefits Alzheimer’s Patients
Brett Smith for redOrbit.com — Your Universe Online
A controversial drug may have a new lease on life as researchers at the University of Texas Medical Branch at Galveston have found it could have unintended benefits for people with Alzheimer´s disease.
The anti-insulin-resistance drug rosiglitazone, marketed by Glaxo-Smith Kline as Avandia, has been shown to enhance learning and memory in mice that have been genetically engineered to serve as models for Alzheimer's patients, according to the researchers report in the Journal of Neuroscience.
If rosiglitazone were found to have a significant benefit for Alzheimer´s patients, it would join other drugs that are prescribed for “off label” use, like Viagra, which the FDA has approved for treating pulmonary hypertension and increasing blood flow as a way to avoid amputations.
"Using this drug appears to restore the neuronal signaling required for proper cognitive function," said UTMB professor Larry Denner, the lead author of a paper. "It gives us an opportunity to test several FDA-approved drugs to normalize insulin resistance in Alzheimer's patients and possibly also enhance memory, and it also gives us a remarkable tool to use in animal models to understand the molecular mechanisms that underlie cognitive issues in Alzheimer's."
In their report, the scientists said the drug produced this cognitive effect by reducing the negative influence of Alzheimer's on a key brain-signaling molecule, extracellular signal-regulated kinase (ERK). In the brains of the genetically modified mice, the molecule becomes hyperactive and this excessive activity disrupts synaptic transmission between neurons. The result, scientists say, is the disruption of learning and memory.
By bringing ERK signaling back into line, rosiglitazone corrects this signaling disruption and allows for proper cognitive functioning.
Researchers at UTMB said they were aware of the connection between ERK signaling and Alzheimer´s, but were unable to put together the pieces necessary for a complete picture. The latest breakthrough only came after an interdisciplinary team of animal cognitive neuroscientists, biochemists, molecular biologists, mass spectrometrists, statisticians and bioinformaticists was assembled at the university.
"We were extraordinarily lucky to have this diverse group of experts right here on our campus at UTMB that could coalesce to bring such different ways of thinking to bear on a common problem," Denner said. "It was quite a challenge to get all of these experts communicating in a common scientific language. But now that we have this team working, we can move on to even more detailed and difficult questions."
The results of the new study could be a boost for rosiglitazone. Approved by the FDA in 1999 as an anti-diabetic drug, Avandia sales peaked at around $2.5 billion in 2006. In 2007, the FDA began investigating the drug after receiving reports it played a role in increased heart attack risk. That investigation concluded Avandia did not significantly increase the risk of heart attack.
In 2010, the Senate Finance Committee, in a panel investigation, found GSK documents that suggest the company downplayed scientific findings about potential Avandia safety risks. That panel eventually resulted in a mixed vote, resulting in the drug staying on the market, but with a revised warning label.
In 2012, the Justice Department announced that GSK had agreed to pay a $3 billion fine and plead guilty to charges it had withheld the results of two studies on the drug´s cardiovascular safety between 2001 and 2007.