Search for answers for heart-breaking illness
In a pioneering clinical trial that
will attack Alzheimer’s disease by targeting inflammation in the brain’s blood
vessels, researchers at the George & Anne Ryan Institute for Neuroscience
have received regulatory approval to initiate the BEACON Study.
This URI-sponsored study is the
first-ever clinical trial led and conducted entirely within the state designed
to treat individuals with mild cognitive impairment probably due to Alzheimer’s
disease and those diagnosed with mild Alzheimer’s disease.
Alzheimer’s research clinics at
Rhode Island Hospital, Rhode Island Mood and Memory Research Institute, and
Butler Hospital will be enrolling participants later this year for this
uniquely Rhode Island study.
“Keeping this study in Rhode Island was important to us,” said Paula Grammas, Ph.D., executive director of the Ryan Institute. “This state has a world-class and closely-linked community of researchers and clinicians, which enables us to pull together resources and make progress quickly.”
The study is funded through a grant
from the Alzheimer’s Drug Discovery Foundation (ADDF) along with private
donations. The ADDF catalyzes and funds drug discovery and drug
development for Alzheimer’s disease and related disorders.
This research is also made possible
by an independent grant from Boehringer Ingelheim Pharmaceuticals, Inc., which
is providing the active drug for this study, dabigatran. URI’s Pharmaceutical
Development Institute is providing the placebo comparator for this trial.
“The role of the vasculature in
Alzheimer’s disease has been grossly under-recognized until relatively
recently,” said Dr. Howard Fillit, Founding Executive Director and 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 to repurpose an existing drug to treat the
vascular abnormalities in Alzheimer’s disease.”
Decades of clinical trials have
brought no treatments that slow or stop Alzheimer’s disease, and only a few
have been approved to treat its symptoms. Most of these studies have targeted
amyloid-beta, a protein which accumulates in the brains of patients.
The lack of successful trials
targeting amyloid has caused some researchers, including Grammas, to study
whether targeting other possible causes of the disease could be a productive
approach.
BEACON is a Phase I clinical trial
that looks into the possible role of the brain’s blood vessels in Alzheimer’s
disease.
Grammas’s 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 BEACON Study repurposes an
existing drug, dabigatran, FDA-approved to reduce the risk of stroke and
systemic embolism in patients with non-valvular atrial fibrillation and for the
treatment and to reduce the risk of reoccurrence of deep venous thrombosis and
pulmonary embolism, to suppress one part of the inflammation process associated
with Alzheimer’s disease.
Results from the BEACON Study are
expected in late 2020.
“If the drug shows some effects on
the progression of Alzheimer’s disease, it would be the first time we’ve found
evidence of a treatment that could slow the disease,” says Grammas. “But even
if the study’s results are less conclusive, this is a vitally important step
forward in expanding our knowledge of the multiple factors that cause this
complex disease. I’m very excited to see what happens.”
Innovative Approach Uses Existing
Drug to Target Inflammation in Brain Blood Vessels
Alzheimer’s disease is one of the
most pressing global health challenges. 5.2 million Americans are affected by
the disease, with costs of care estimated to be $259 billion in 2017.
While there are medications to
address some of the symptoms of Alzheimer’s, there are currently no approved
treatments that can prevent, slow, or cure the disease.
Meanwhile, despite decades of
research, many of the factors that are likely to play a role in Alzheimer’s
disease, such as inflammation, the immune system, and the brain’s vasculature,
have remained largely under-explored. The Ryan Institute
(ryaninstitute.uri.edu) has been a leader in investigating these critical
factors.
The BEACON Study is based on 30
years of research by Dr. Grammas and her team. They were the first to identify
an inflammatory cascade in which injury to the cells lining blood vessels in
the brain (known as endothelial cells) “activates” them, causing the release of
a number of different molecules harmful or toxic to nerve cells.
Grammas’s research has shown that
thrombin, a protein involved in blood clotting, may be a key driver in this
process. The BEACON Study will look at the effects of the drug dabigatran, a
direct thrombin inhibitor, to slow down this harmful cascade in the early
stages of Alzheimer’s disease.
In preclinical studies using rodent
models of Alzheimer’s disease, the treatment significantly slowed
neurodegeneration, and drugs with similar action slowed the decline of
cognitive function. BEACON stands for “Blocking Endothelial Activation to Curb
the Onset of Neurodegeneration.”
How to Learn More About
Participating
If you are in good health, between
50 and 85 years old, and interested in learning more, please contact the BEACON
Study information line at (401) 874-5650 or email us at beaconstudy@uri.edu.