Recently the University of Rhode Island and Alzheimer's Drug Discovery Foundation announced The BEACON Study (Blocking Endothelial Activation to Curb the Onset of Neurodegeneration), a phase 1 clinical trial that will explore a new approach to treating Alzheimer's disease by using a repurposed drug to target inflammation in brain blood vessels.
For me, this proof-of-concept trial isn't just the culmination of 30 years of my research into the role brain blood vessels may play in Alzheimer's disease. It also marks a necessary shift in the way we think about the disease and highlights the role the ADDF has played in making that possible.
In the late '80s, when I first began looking at brain blood vessels in Alzheimer's disease, there was little interest in this area of research. Most of the field was centered on pursuing a sole target, the amyloid protein. The resulting amyloid cascade hypothesis has dominated Alzheimer's research and research funding for the last 30 years. Although pursuit of this hypothesis has yielded some gains in our understanding of the disease, it has yet to lead to any disease-modifying treatments. In the meantime, evidence continues to grow that Alzheimer's is a complex disease in which cardiovascular risk factors, blood vessels, inflammation, and the immune system are likely involved.
Our laboratory has worked to understand how abnormal brain blood vessels may drive neuronal cell death in Alzheimer's disease. Enrolling this spring, the BEACON Study is based on our findings that injury to brain blood vessels—caused by factors such as diabetes, high blood pressure, or high cholesterol—activates a toxic cycle of vascular-derived neuroinflammation that is linked to neuronal cell death. We have identified the protein thrombin as a key mediator of this pathologic cycle. In a pre-clinical study using animal models of Alzheimer's disease, treatment with a thrombin inhibitor reduced this vascular-derived neuroinflammation and improved cognitive performance, supporting the validity of targeting vascular activation as a potential therapeutic entry point.
One of the most exciting parts of this approach is that we will repurpose an FDA-approved drug, dabigatran, to inhibit thrombin. Finding a drug that has already been vetted by the FDA could mean an Alzheimer's therapy that is available years earlier.
Our ability to pursue an "out-of-the-box" approach to Alzheimer's therapies is due in no small part to the ADDF, which has been at the forefront of supporting research into new targets for Alzheimer's treatment and making studies like BEACON possible. The ADDF has also been a leader in supporting research into the use of repurposed drugs as novel therapeutics for Alzheimer's disease.
I am grateful to the ADDF not only for their engaged and committed support of The BEACON Study, but for a long track record of pushing research forward in a field that desperately needs to make gains. Their work has made the difference not only in our lab here at URI, but for researchers across the field and to the millions of people counting on a breakthrough sooner than later.
Paula Grammas is the Executive Director of the George & Anne Ryan Institute for Neuroscience at the University of Rhode Island. The BEACON Study will begin enrolling in April 2019.