A drug originally designed to target cancer has been found to restore memory and reverse cognitive problems in mice with Alzheimer’s disease-like symptoms and could offer a path forward to a treatment for humans someday, a new study found.
Yale University researchers found that the previously approved drug, saracatinib, targeted beta amyloid deposits and reduced their toxic effect on surrounding brain cells. The buildup of beta amyloid in the brain can be a precursor of Alzheimer’s disease in the aging brain.
The study – which appeared earlier this month in the Annals of Neurology — was carried out in collaboration with the National Center for Advancing Translational Sciences (NCATS), a three-year-old high-tech facility in Rockville. NCATS, which is part of the National Institutes of Health, is designed to transform pure research into practical results as quickly as possible.
Francis Collins, head of the NIH, called attention to the study as one of the first fruits of NCAT’s approach to developing biochemical research during a tour Tuesday of the facility with Sen. Barbara Mikulski (D-Maryland).
Mikulski said the test results are one reason why she is pushing to increase NIH’s funding of $30 billion a year by 10 percent this year, with steady and more regular funding streams pushing the total to $45 billion by 2020. During the tour, she said she believed people would look back at this time someday and see that Alzheimer’s research was on the cusp of major advances just as cancer research was a few decades ago.
“This could be as important as landing on the moon,” Mikulski said.
An estimated 5.3 million people have Alzheimer’s disease, which is the leading cause of dementia in the United States. The Alzheimer’s Association, in its most recent report says about 454,000 new cases of Alzheimer’s were diagnosed in 2010. As demographic shifts raise the overall age of the population, that number will rise to an estimated 615,000 by 2030, the report says.
Christopher P. Austin, NCAT’s director, said its mission involves both using theoretical models and vast amounts of data on chemical compounds and cellular processes to search for breakthroughs and make the process more predictable. At the same time, the center is stocked with robotics and other technology to speed up the trial-and-error of laboratory tests.
He said the center has focused on off-purpose uses of approved drugs that could be useful in treating ailments for which they weren’t initially intended– just like Viagra, which was originally developed to treat high blood pressure and proved useful for treating erectile dysfunction.
“We’re systematizing serendipity,” Austin said in an interview at the site. Instead of technicians in lab coats using pipettes and petri dishes, the center uses robotic arms and “tissue chips” – which resemble bionic combinations of microchips and living stem cell cultures – to run thousands of tests at once. They can not only try out a promising chemical compound but experiment with the proper dose. Austin said the machines can conduct about three million such tests in a week, compared with the run of experiments that might have taken 12 years a couple decades ago.
“The major victory here is the mechanism by which it happened,” Austin said.
Efforts to identify previously approved drugs for off-label purposes to treat Alzheimer’s have gained momentum in recent years, Austin said. Earlier this year, the French pharmaceutical company Pharnext announced that a combination of two drugs — acamprosate calcium, which has been prescribed since 1989 to reduce cravings and alleviate withdrawal symptoms in alcoholics, and baclofen, a medication that has been used for decades to treat the spastic movements in people suffering from multiple sclerosis — had also shown promising results a as potential Alzheimer’s treatment someday.
Similarly, Stephen Strittmatter, a Yale neurobiology researcher, and his colleagues investigated the medication saracatinib, which had been developed by AstraZeneca, as a way of targeting a protein called Fyn kinase that plays a central role in the way that beta amyloid attacks surrounding neurons.
They then gave the drug to mice that have been genetically modified to develop Alzheimer’s-like physiological and cognitive symptoms, including the buildup of beta-amyloid in brain tissue and memory loss. After four weeks, the mice showed a reversal in their memory loss and difficulties with spatial learning. An examination of their brain tissue showed that the characteristic synapse loss had been restored.
The study first appeared March 21 in the Annals of Neurology. Although the researchers said the results were promising, they also cautioned that more work must be done before scientists know whether the drugs would work similarly on humans.
“We are excited about this advance,” Austin said. “But this is the first lap, not the final lap.”