The George & Anne Ryan Institute for Neuroscience was created to support basic research and translational medicine with a view to understanding neurodegenerative diseases and finding ways to treat or cure them. We invite researchers and those in the pharmaceutical and healthcare industries who share these interests to join in our work.
Learn more about Ryan Institute Affiliations.
Current Research Initiatives
Exploring how inflammation of blood vessels in the brain may contribute to the onset and progress of Alzheimer’s Disease.
Alzheimer’s disease (AD) is an insidious disease that robs patients of even their own identities: cherished memories, the ability to recognize loved ones, and, eventually, the ability to relate to the world around them. Its impact on patients, families, and the health care system in the U.S. alone is estimated at $236 billion per year*. There are no effective treatments or cures.
Researchers looking for the causes of AD and ways to treat it have traditionally focused on two proteins associated with the damaged brain tissue seen in autopsies of Alzheimer’s victims: beta amyloid and tau. The working hypothesis has been that the accumulation of these proteins is the principal disease mechanism.
There is mounting evidence, however, that the brain’s blood vessels may play a role in triggering some forms of AD. Paula Grammas, director of the Ryan Institute, is a leading figure in this line of research. Her work has shown that when the endothelial cells that line blood vessel walls are activated, they release neurotoxic inflammatory proteins such as thrombin and interleukins. Pharmaceuticals that block the endothelial response also reduce the behavioral and memory deficits in mice with a condition similar to AD.
The environment may contribute to neurodegenerative disease.
The proper expression of gene activity is crucial to an organism’s development, life, and aging. A remarkable ballet occurs in our cells as genes are activated and deactivated to direct the production of the specific proteins that make each cell function appropriately. Epigenetics is the study of the biochemical and molecular-biological mechanisms that choreograph this ballet of gene expression. Epigenetic modifications include chemical changes to the proteins that influence the accessibility of specific genes, changes in the position of nucleosomes (important in the packaging of DNA) and the inhibition of gene translation by small non-coding RNA known as microRNA (miRNA).
URI researcher Nasser Zawia was one of the first investigators in the world to show that exposure to environmental toxins in early life produces changes to the neural epigenome. His laboratory has provided evidence that these epigenetic changes may lead to the cellular damage and neuronal death that occur in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Zawia and his colleagues hope to use this growing awareness of epigenetic modifications in neurodegenerative diseases to discover and develop disease-modifying therapies that restore the proper balance of gene expression in the brain.
Interfering with harmful neuroinflammatory responses could reduce disease-related damage to healthy neurons and slow the pathological and cognitive impacts of disease.
There is tremendous potential in targeting the immune system to treat brain disease, from a scientific, therapeutic, and commercial perspective. Aberrant immune system activity and consequent neuroinflammation has been associated with virtually every major neurodegenerative and neuropsychiatric disorder. In addition, the immune system may actually attack the brain as if it were a foreign pathogen. Being able to interfere with or prevent this maladaptive, pathological immune activity could lead to breakthrough treatments.
Four neuropharmacology researchers previously with Pfizer, Lundbeck and Mnemosyne Pharmaceutical companies—Stevin Zorn, Frank Menniti, Bob Nelson and Brian Campbell—have formed a new company, MindImmune Therapeutics, Inc., which focuses on targeting specific enzymes and cell surface receptors associated with immune cells to inhibit the deleterious neuroinflamatory actions that they produce in the central nervous system—a response that, if unimpeded, can cause significant damage to healthy neurons leading to or exacerbating disease.
As partners with MindImmune, the Ryan Institute is home base for the company’s research and discovery work, and helps facilitate access to the larger neuroscience community. The partnership has also enabled MindImmune to establish itself in Rhode Island and serve as the nucleus of an anticipated innovation center affiliated with the university
Studies have identified pharmaceuticals—already approved for use in humans—that have potential use against Alzheimer’s disease. For instance, the anti-cancer drug sunitnib reduces biochemical and behavioral symptoms in mouse models of the disease. Another research team has studied transcription factor specificity protein 1 (Sp1), which is closely linked to the expression of the genes for several Alzheimer’s-associated proteins, and found that tolfenamic acid lowers the expression of those genes. Tolfenamic acid has been designated as an orphan drug to treat neurodegenerative diseases by the European Medicine Agency (EMA) with FDA approval pending.
Understanding the chemical and molecular bases of why plant natural products such as pomegranate may lessen the effects of Alzheimer’s disease.
The modern pharmaceutical industry arose from the study of plants with medicinal and other therapeutic value. In recent years researchers have returned to these roots, once again searching for new drugs in nature. Armed with the tools of molecular biology and chemical analysis, we are now better equipped to find and understand the effects of specific compounds.
In the case of Alzheimer’s disease, the pomegranate shows promise. Ryan Institute researcher Navindra Seeram has demonstrated that pomegranate juice and extracts seem to protect neurons from damage in several animal models of the disease. Seeram and his colleagues also have found that urolithins, which are formed when mammalian microbial bacteria metabolize pomegranate compounds, inhibit the formation of filaments of the Alzheimer’s-associated protein beta-amyloid. Furthermore, urolithins also reduced beta-amyloid toxicity in a transgenic strain of the nematode Caenorhabditis elegans.
Easing epileptic seizures with non-invasive electrical stimulation.
Technology has been used for decades to study the brain, whether through electrodes that record nerve activity or microscopes that image the anatomic and functional connections that underlie the processing of information. In recent years these technologies and more have been finding new roles in delivering treatments.
Epilepsy is a disorder that sends the brain into sustained spasms of uncontrolled activity, accompanied by behavioral changes such as seizures. Immediate treatment is vital to minimizing brain damage, but existing treatments are not fully effective. Walter Besio, an associate professor of biomedical engineering, and colleagues are working to develop a real-time, non-invasive electrical stimulation system that would reduce the severity of epileptic seizures.
In his studies in rats, small discs containing concentric circular electrodes are attached to the scalp, positioned so that they focus electrical stimulation on the areas where seizures originate. His research has not only found these tripolar electrodes to be more effective, it has also allowed him and his collaborators to study the relationship between epileptic activity and brain biochemistry, tracking down pathological mechanisms that may support other therapeutic methods.
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