On March 31, 2015, the National Institutes of Health (NIH) reported that a drug originally developed to treat cancer, might be an effective treatment for Alzheimer’s disease. The study demonstrated that the drug saracatinib restores memory loss and reverses brain problems in an animal model of Alzheimer’s. Clinical trials are now underway to test the effectiveness of saracatinib in humans.
Dementia conditions are a group of disorders that cause progressive loss of memory and other mental processes. Alzheimer’s disease is the most common form of dementia. There are an estimated 72,000 (2014 data) people living with Alzheimer’s in Connecticut (5.2 million in the United States). As the baby boomers age, the number of Americans with Alzheimer’s disease will increase rapidly. Unless medical breakthroughs to prevent, slow, or stop the disease are found, by 2050, the number of people with Alzheimer’s disease will nearly triple (from 5 million to 16 million).
Alzheimer’s disease causes clumps of amyloid beta protein to build up in the brain. These protein clusters damage and ultimately kill neurons (brain cells). Alzheimer’s disease also leads to loss of synapses – synapses are the spaces between neurons through which the cells talk to each other and form memories.
Previous studies indicate a protein called Fyn kinase plays a central role in how amyloid beta clusters damage brain cells. Saracatinib (AZD0530), a drug previously developed to treat cancer, targets this Fyn protein. Saracatinib has already cleared several key steps in the drug development process. Typically, drug development takes at least ten years – from the discovery of a therapeutic target to an experimental compound’s entry into a Phase 2 human clinical trial to test effectiveness. In the case of saracatinib, the research team completed preclinical and clinical safety studies and began a Phase 2 trial within about 18 months. “The investigational drug already had been developed, optimized, and studied in animals as well as tested for safety in humans. [This] gave us an incredible shortcut in the drug development process,” explains Stephen Strittmatter, M.D., Ph.D.
In this recent study, mice with Alzheimer’s-like symptoms were treated with saracatinib. After four weeks, the Alzheimer’s mice showed complete reversal of spatial learning and memory loss. Examination of the brains of these mice showed that the characteristic synapse loss had been fully restored. This provides a biological explanation for the memory improvement. The treatment also reduced several other Alzheimer’s-related biochemical changes in the mice and did not appear to be toxic. Results of this study are published in the Annals of Neurology.
This study was conducted with the help of the National Center for Advancing Translational Sciences (NCATS) Discovering New Therapeutic Uses for Existing Molecules program. This program, launched in 2012, matches scientists with pharmaceutical industry drugs to test potential ideas for new therapeutic uses. The pharmaceutical industry has already performed significant research and development on these drugs, including safety testing in humans. “This work demonstrates what can happen when NIH, the biopharmaceutical industry, and academia innovate and collaborate to share resources and knowledge,” said NCATS Director Christopher P. Austin, M.D. “The speed with which this compound moved to human trials validates our New Therapeutic Uses program model and serves NCATS’ mission to deliver more treatments to more patients more quickly.”
A successful Phase 1b safety trial of saracatinib in humans with Alzheimer’s disease has already been completed (clinicaltrials.gov trial number NCT01864655). A larger, multi-site Phase 2a trial (NCT02167256) to assess safety, tolerability, and effectiveness of saracatinib is currently in progress. Participants in this clinical trial will receive saracatinib or placebo for one year. Results of this trial are expected within two years. Anyone interested in participating in this clinical study can find more information here or at clinicaltrials.gov.