Stephen Strittmatter, M.D., Ph.D. | Alzheimer's Association

Stephen Strittmatter, M.D., Ph.D.

Yale University School of Medicine
New Haven, Connecticut
2014 Zenith Fellow

Repurposing a Cancer Treatment for Alzheimer's Disease

Dr. Stephen Strittmatter has received multiple awards from the Alzheimer's Association and over $16 million in National Institutes of Health (NIH) funding related to Alzheimer's and other dementias research. His research has focused on investigating the sites where toxic forms of beta-amyloid called oligomers interact on nerve cells. He found that beta-amyloid oligomers can attach to a natural cell protein called Prion Protein (PrP) that is involved in neurodegeneration, most notably the human form of "mad cow" disease, called Creutzfeldt-Jakob disease, which is ultimately fatal.

Dr. Strittmatter and colleagues found that interactions between beta-amyloid and PrP can lead to abnormal activation of the Fyn kinase system, a complex biological pathway involved in memory processes. Through a series of elegant studies, they found that Fyn kinase and PrP are required to mediate beta-amyloid toxicity and subsequent memory problems observed in Alzheimer's-like mice.

This line of research has helped lead to the identification of targets that may be at the root of the disease process. Most recently, Dr. Strittmatter has focused on therapeutic strategies that target the Fyn kinase pathway. Of great interest was the finding that a drug that blocks Fyn kinase called Saracatinib already had been developed by the pharmaceutical company AstraZeneca to treat cancer. Saracatinib was found to be safe in humans but ineffective in treating myeloid leukemia, so it was put on the shelf. However, Saracatinib has taken on new life through an innovative program, Discovering New Therapeutic Uses for Existing Molecules, administered through the National Center for Advancing Translational Sciences (NCATS), the newest of the NIH institutes. The program's goal is to repurpose therapeutics that have undergone extensive research and development by pharmaceutical companies and match them to academic researchers such as Dr. Strittmatter to accelerate their scientific research. This matching can reduce the drug development time by as much as a decade because the repurposed compounds already have undergone extensive animal and human testing.

Thanks to this program, Dr. Strittmatter has partnered with AstraZeneca to launch directly into clinical trials to test the role of Saracatinib in treating Alzheimer's. Currently he is leading an active Phase II human clinical trial to continue testing the safety of the drug and to determine its effectiveness in reducing cognitive impairment and improving brain function. It is exciting to move this concept into clinical trials in such a short time. Dr. Strittmatter's work shows how the Association's support can help launch an idea that can rapidly move into the clinical setting and show promise as a therapy to change the course of Alzheimer's.




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