The drug to be tested, dabigatran, has been shown to reduce “thrombin-induced inflammation,” believed to be a factor in Alzheimer's.

SOUTH KINGSTOWN — In what is a first for the University of Rhode Island and a potential landmark development in Alzheimer’s disease research and treatment, the school’s Ryan Institute for Neuroscience is set to begin an investigational drug trial that differs from other interventions that have been tested to prevent or reverse the fatal disease.

Most other drugs that have been tested, with varying results, have been aimed at the abnormal buildups of amyloid protein and tau proteins that cause brain plaques and tangles, harming function. The URI study will target inflammation of the blood vessels that supply the brain and its billions of neurons — an area of research in which Ryan director Paula Grammas has long specialized, initially to the skepticism of other scientists in the field.

“The fact that we're testing this hypothesis is important because there's more and more emphasis now in the field to look at things beyond amyloid,” Grammas told The Journal. “Alzheimer’s disease is likely many different mechanisms producing Alzheimer's at the end and we have said that we really want to look at how brain blood vessels play a critical role in this death process in the brain.”

The drug to be tested, dabigatran, is already approved by the Food and Drug Administration to reduce the risk of embolism and stroke and for certain patients with an irregular heart rhythm. Dabigatran has been shown to reduce “thrombin-induced inflammation,” believed to be a factor in Alzheimer’s.

“Grammas’ research has shown that factors such as high blood pressure, diabetes, and stroke can injure blood vessels in the brain, resulting in inflammation that could cause the damage or death of brain cells that occurs in Alzheimer’s disease,” the Ryan Institute said in announcing the trial.

The final cost of the study is expected to be from $1.3 million to $1.5 million, according to the institute. It is being funded by private donations and a grant from the Alzheimer’s Drug Discovery Foundation. Microsoft founder Bill Gates is among those who last year committed $30 million to a new foundation initiative to develop new tests to diagnose Alzheimer’s.

Also contributing to the study is Boehringer Ingelheim Pharmaceuticals, Inc., which is providing the dabigatran to be used in the study.

Known as the BEACON study, for Blocking Endothelial Activation to Curb the Onset of Neurodegeneration, the URI trial will involve participation by the Rhode Island Mood and Memory Research Institute and Care New England's Butler Hospital, where Dr. Stephen P. Salloway heads the Memory and Aging Program, another leading Alzheimer’s center.

“The BEACON clinical trial is an important milestone in the history of the University: the first time URI has sponsored a drug treatment clinical trial,” URI president David M. Dooley, whose background includes years as a research scientist, said in an email to The Journal.

“It is a clear example of the vision behind Tom and Cathy Ryan's gift to establish the Ryan Institute for Neuroscience, where this type of transformative work has tremendous potential to set a new direction in Alzheimer's disease research. The partnerships between URI and clinical sites at Rhode Island Mood and Memory Institute, Butler Hospital, and Rhode Island Hospital speak to the uniquely productive environment for neuroscience in Rhode Island.”

“The role of the vasculature in Alzheimer’s disease has been grossly under-recognized until relatively recently,” said Dr. Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation: “As a result, strategies to develop therapeutics to address this important part of the disease have been lacking. We are pleased to work with Dr. Grammas and fund her work using a very novel approach.”

Said Grammas: "Should it work, that would be amazing ... I would say that what we're targeting has a good chance of being successful maybe in a good percentage of patients." Success in this initial study, she said, could encourage larger studies leading to adoption of dabigatran as an intervention.

But Grammas shared with The Journal her belief that the mechanisms involved in Alzheimer's remain, in part, mysterious. "It's a very complicated disease that has likely multiple etiologies," or causes, she said.

The Ryan Institute is looking to enroll 40 to 60 participants in the new drug trial, expected to last two years. Candidates must be between 50 and 85 years old and already diagnosed with milder cognitive impairment or mild Alzheimer’s disease but otherwise are in good health. To learn more, call the BEACON Study information line at (401) 874-5650 or email beaconstudy@uri.edu

The public is also invited to "A Conversation about Alzheimer's," an evening featuring expert and patient speakers and free memory screenings. The event on Jan. 24 begins with screenings at 4:30 p.m. and continues with the speaking program from 5:30 p.m. to 7:30 p.m. at URI's Higgins Welcome Center, 45 Upper College Rd., Kingston. Registration is required: Call (401) 874-5650 or email beaconstudy@uri.edu

Watch a Ryan Institute video explaing the role of inflammation in Alzheimer's: https://www.youtube.com/watch?v=Aq02qLDJnEk