Funding Some Big Ideas
Ryan Institute supports interdisciplinary research and outreach on brain-healthy lifestyles
The Ryan Institute is collaborating with the URI Institute for Integrated Health and Innovation (IIHI) to support two of the projects that were selected for IIHI funding as part of the “Big Ideas in Health” initiative. Each project will receive matching funds from the Ryan Institute, doubling the $10,000 granted by IIHI.
The first team, led by Research Professor Colleen Redding, Ph.D., a member of the Ryan Institute Faculty as well as the URI Cancer Prevention Research Center, will study the public’s understanding of the connection between behavior and brain health—the first step to developing more nuanced and effective interventions to improve health across communities.
The second, led by Professor of Nursing Instruction Pat Burbank, D.N.Sc., brings together faculty from nursing, nutrition, kinesiology, engineering, and gerontology to study the feasibility of developing a URI-affiliated senior housing community.
The Ryan Institute is also granting $10,000 in seed funding to explore how changes in posture and gait can indicate cognitive decline. Movements such as standing and walking may appear simple and routine, but they in fact involve coordination among multiple brain centers—some of the same areas of the brain whose function deteriorates in people with dementia.
This project, led by Kim Fournier, Ph.D., and Christie Ward-Ritacco, Ph.D., brings in faculty from several other URI departments including Cell and Molecular Biology and Psychology. The researchers hope to learn whether body position and movements, which can be measured quantitatively using biometric equipment, could be useful biomarkers for early stages of dementia and neurodegenerative disease.
NSF Grant Supports Networked Clothing for Parkinson’s Disease
Ryan Institute faculty member Kunal Mankodiya has received a $525,000 CAREER grant from the National Science Foundation to continue his innovative work on “smart textiles,” garments embedded with sensors and electronics that collect data and relay it to caregivers.
Mankodiya, Assistant Professor of Biomedical Engineering and Ryan Research Assistant Professor of Neuroscience, has focused on creating gloves, socks, and shoes to aid people with Parkinson’s disease.
Mankodiya is also part of the Ryan Institute’s lifestyle initiative, an interdisciplinary project developing research and outreach to help people make choices that will reduce the likelihood of developing neurodegenerative diseases.
Read more about Mankodiya and the grant at URI Today.
Photo: Michael Salerno
Seminar: The Impact of DNA Methylation on Neuropathology: Understanding Disease and Searching for Biomarkers
Paula Desplats, Ph.D.
Assistant Professor of Neurosciences and of Pathology University of California San Diego School of Medicine San Diego, CA
Parkinson’s and Alzheimer’s diseases are the most prevalent neurodegenerative disorders in the aging population and their incidence is growing exponentially. The multifactorial etiology of these diseases encumbers the development of improved therapeutic strategies to eventually cure them. Emerging evidence now supports the involvement of epigenetic mechanisms in neurodegeneration, adding a new layer of complexity to pathology. However, the mechanisms that contribute to alterations in DNA methylation and its role in disease trajectory remain poorly understood. Research at the Desplats lab combines basic mechanistic studies and translational research to investigate the dynamics of DNA methylation that may be associated with disease, including the role of methylation on circadian impairment in Alzheimer’s disease, as well as the exploration of the potential of methylation as a novel biomarker for the diagnosis of Parkinson’s disease and related disorders.
Dr. Desplats is a candidate for Associate Professor in the George & Anne Ryan Institute for Neuroscience.
Wednesday, April 5, 2017
Room 240, College of Pharmacy
Blood Protein May Offer New Approaches to Alzheimer’s Disease Therapy
Thrombin is well known for its role in blood clotting and other inflammatory response processes. New evidence from the Ryan Institute suggests it may be a good target for therapies to head off Alzheimer’s disease.
Previous work in the lab of Executive Director Paula Grammas showed that blocking inflammatory processes in blood vessels in the brain improved cognitive performance in mice which develop an Alzheimer’s-like disease. The compounds used in those studies are not suitable for clinical trials in human Alzheimer’s disease patients, however. Thrombin, on the other hand, is the target of several FDA-approved medications that inhibit its function. It’s also one of the first proteins released during the inflammatory process; these two factors made it a promising subject for new studies.
In a presentation at the 2017 Clinical Trials on Alzheimer’s Disease conference, Grammas presented early evidence that inhibiting thrombin with the drug dabigatran reduces the production of other inflammatory proteins, affecting the biochemical pathways previously linked to neurodegeneration. The effect was observed in two different systems: when inflammatory responses were provoked by reducing the oxygen available to isolated brain-blood-vessel cells in culture, and when dabigatran was given to Alzheimer’s-like mice.
These new observations extend the connection between blood brain vessels and Alzheimer’s disease and highlights its potential as an innovative route to treating Alzheimer’s disease and dementia.
Learn all about your amazing brain at the URI Brain Fair!
March 18, 2017
10 a.m.–2 p.m.
URI College of Pharmacy, 7 Greenhouse Rd., Kingston RI
This free, family-friendly event will feature creative, hands-on demonstrations and activities that
will entertain, educate and inspire.
We’ll have food and lots of giveaways!
- How surfing and balance are used to help children with disabilities
- How music helps brains grow and stay healthy
- How the connections between parts of your brain help it process information
- How exercise, a healthy diet, and mindfulness are good for your brain
- What it’s like to suffer from Alzheimer’s disease and dementia
- How your brain makes decisions
- Why some people are color blind
Parking: Ample parking is available along Flagg Rd., or in the Fine Arts Lot between Flagg Rd. and Bills Rd.
For more information: email firstname.lastname@example.org or call 401.874.4471 or 401.874.2399.
The URI Brain Fair, sponsored by the George & Anne Ryan Institute for Neuroscience, is part of Brain Week Rhode Island, a celebration of brain health and brain science for all Rhode Islanders.
Ryan Institute Faculty Key Players in NY Academy of Science Symposium
Conference brings together experts on the role of inflammation in Alzheimer’s
Digging into unorthodox ideas about the origins of neurodegenerative disease is the heart of the Ryan Institute’s work. It was also the idea behind a recent symposium at the New York Academy of Sciences. “Alzheimer’s Disease as a Neurovascular Disorder” brought together more than 200 researchers, medical professionals, and patient advocates to discuss what is still seen as a radical proposition: that abnormal brain blood vessel function can lead to or worsen Alzheimer’s disease.
“The impact of bringing together a group like this is significant,” said Ryan Institute Executive Director Paula Grammas, Ph.D., who spoke at the meeting. “We’re all trying to move this research in new directions, and collaboration and discussions about what we’re doing will help make that happen.”
One co-chair of the conference was Robert Nelson, Ph.D., Ryan Research Professor of Neuroscience and vice president of MindImmune Therapeutics Inc., a pharmaceutical startup based at URI in partnership with the Ryan Institute. Nelson emphasized that the seminar brought together experts who are taking Alzheimer’s research in new directions.
“There is much disappointing news emerging from Alzheimer’s clinical trials,” Nelson said, referring to several clinical trials in which therapies were tested for their ability to reduce deposits of amyloid-beta, a protein which has been linked to Alzheimer’s disease. “We hoped to highlight that the ‘amyloid hypothesis’ is just one piece of the larger puzzle. Progress has been held back when researchers argue about whether the root cause is amyloid or tau,” another protein whose links to Alzheimer’s disease have been intensely studied, “or inflamed blood vessels. All of these are features of Alzheimer’s.” To achieve a holistic understanding of the disease, he says, researchers must share their findings and look for common ground.
Grammas, in her presentation, wove together data from her lab with the work of other researchers to make the case that cerebrovascular dysregulation contributes to the development of Alzheimer’s—a line of research she has pursued for thirty years which is gaining increasing attention.
Other presentations addressed the importance of preventing inflammation associated with risk factors such as diabetes, high blood pressure, and high cholesterol; understanding communication among the brain and the immune and vascular systems; and the correlation between strokes and cognitive changes in the brain.
Nelson says the conference advanced the science of neurodegenerative disease, and also that “it struck a note of hope amid the disappointment we’ve all felt about recent clinical trial failures.”
MindImmune Nets Innovation Voucher
MindImmune Therapeutics, Inc., a biotech startup based at URI in partnership with the Ryan Institute, was one of six companies to receive innovation vouchers from the Rhode Island Commerce Corp. The vouchers are intended to spur research and development partnerships; MindImmune’s $50,000 voucher will fund collaboration with the URI Comparative Biology Resources Center. MindImmune is exploring neuroimmunology-based drug therapies for Alzheimer’s disease and other neurodegenerative diseases.
Solanezumab Trial Fails: Now What?
The failure of solanezumab in its most recent clinical trial is the loudest call to action yet for us to widen the search for new explanations of Alzheimer’s disease and new ways of treating it.
Solanezumab was designed to reduce the amount of amyloid protein in the brain. Amyloid is the primary component of amyloid plaques, one of the principal pathological hallmarks of Alzheimer’s disease. Amyloid and another protein, tau, have been at the hub of Alzheimer’s disease research for the last 30 years, yet Alzheimer’s therapies directed against amyloid and tau have failed across the board. Why?
We’re coming to understand that Alzheimer’s is a very complex disease. More and more scientists and clinicians are saying that it’s time to look for culprits beyond amyloid and tau. Thankfully, we’re not starting from zero: research over the last few decades has found strong evidence that many systems are involved in the disease, including:
Blood vessels: When the brain’s blood vessels are injured (by stroke, high blood pressure, or diabetes, for example), they produce a cascade of molecules that are toxic to nerve cells. Work in my lab and others suggests that interfering with this cascade could slow the disease and preserve cognition.
Immune system: Abnormal immune system activity and inflammation in the brain is associated with nearly every major neurodegenerative disease. At MindImmune Therapeutics, a company based at URI in partnership with the George & Anne Ryan Institute for Neuroscience, scientists are exploring how altering the immune response may alter the course of disease.
Gene activity: Cells use many mechanisms to activate and suppress genes. This complicated network of interactions is vulnerable to environmental toxins, and disrupting the usual balance of gene activity in the brain can harm the function and health of brain cells.
Here’s the trickiest part: Alzheimer’s disease is probably not caused by malfunction in a single system, but by perturbations in multiple areas. Furthermore, each system has many components, any one (or more) of which can go wrong. We have every reason to believe that what we call Alzheimer’s disease is actually a constellation of syndromes with many causes.
What does this mean for treating Alzheimer’s disease? It means that a therapy that targets only one system is unlikely to be effective. It means that what works for one patient might not work for another. It also means that we have multiple potential pathways to interrupt the disease—a source of hope and opportunity. We must redouble our efforts to fill the gaps in our knowledge and convert our discoveries into viable therapies. This is the purpose of the Ryan Institute.
Working it Out
There is now clear evidence that exercise and diet can have a significant impact on the likelihood of developing dementia and Alzheimer’s disease. With that in mind, Ryan Institute Associate Director William Renehan, Ph.D., and special advisor Catherine Taylor, former Director of Elderly Affairs for Rhode Island, have convened a committee at URI to study the treatment of Alzheimer’s disease and cognitive decline with diet and exercise. The committee includes faculty with expertise on nutrition, kinesiology, psychology/cognition, epigenetics, and patient engagement. The goal is twofold: to develop a study that will help define what modifications in diet and what forms of exercise are most beneficial; and to develop an outreach and education program aimed improving the brain health of Rhode Islanders.
Read more about the science behind this initiative in this article by William Renehan.
Image: “My Morning Jump” by whologwhy on flickr. CC-BY-2.0
Systematic Review Supports Association Between Diet and Alzheimer’s Incidence
A thorough review of more than 60 studies supports the idea that what we eat can have an impact on our risk of developing Alzheimer’s disease, but variability in the design and results of those studies makes it difficult to draw more specific conclusions about the most beneficial diet, or how those benefits come about.
Many of the studies tried to evaluate the effect of a “Mediterranean” diet, most often associated with consumption of fruits and vegetables, fish, poultry, and olive oil. Other studies examined vitamins, single nutrients, or classes of nutrients as well as particular beverages such as coffee and wine. The results of the analysis could help shape the design of future studies and interventions on diet and disease.
The review, published earlier this year in the International Journal of Neuroscience, was co-authored by Miryam Yusufov, a URI graduate student now at Harvard Medical School; Ryan Research Professor Lisa Weyandt; and Irene Piryatinsky, Assistant Professor of Psychiatry and Human Behavior at Brown.