Scripps professor receives Research Program Award for advancing RNA-targeting medicines

In recognition of his high-impact work advancing the field of RNA-targeting medicines, the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, has awarded Scripps Research Chemistry Professor Matthew Disney, PhD, a prestigious Research Program Award, to aid Disney's development of treatments for incurable diseases such as Alzheimer's, Parkinson's, ALS and frontotemporal dementia.

The NINDS Research Program Award is designed to enable creative scientists with a proven track record to focus their time and talent on advancing science rather than on writing grant applications. It lasts for five years, is extendable for up to eight, and in Disney's case, is worth up to $11 million cumulatively.

Matt Disney's work has changed the landscape of what scientists now consider 'druggable targets,' and in the process, reinvigorated research on multiple incurable diseases, including muscular dystrophy, ALS and advanced, metastatic cancer. That this prestigious NIH award program has now gone to two of our Florida-based scientists in four years speaks to the world-class, high-impact biomedical research we do."

Douglas Bingham, Executive Vice President, Scripps Research

In 2017, Florida-based Neuroscience Professor Ron Davis, PhD, was among the inaugural group of 30 scientists to receive the NINDS Research Program Award. Davis studies both basic and applied neuroscience, and has discovered biological mechanisms underpinning memory and forgetting, while searching for new treatments for neurodegenerative diseases.

Disney says he plans to use the Research Program Award to advance new treatments for some of the most challenging brain diseases.

"There are millions of patients and their families that have invested their time and their own tissue samples to advance the development of targeted therapeutics," Disney says. "They are awaiting development of new approaches that can be advanced into medicines for brain and nervous system diseases, such as Alzheimer's, Parkinson's and ALS and multiple rare genetic diseases."

Essential for life, RNA carries out fundamental duties in our cells. It templates genes, builds proteins, and regulates multiple cell activities, including how much of a particular protein gets manufactured from our DNA.

Controlling, silencing or repairing RNA, especially toxic RNA that might be garbled, expanded or broken, has been a goal of many scientists through the years. By designing a sort of computational and mathematical decoder, Disney has succeeded against tough odds.

"Our work has developed new ways in which the RNAs that directly cause these disease can be manipulated with chemical probes and in some cases, we can use the body's own defense system to erase disease-driving RNSs," Disney says.

"Armed with these tools and approaches, we are attempting to set a foundation to develop drug-discovery technologies that may allow treatments to emerge. This award will allow us the freedom to pursue these new directions and take risks to go after multiple diseases at once."

RNA is built of simple stuff, just four nucleic acids. Under an electron microscope, it appears more like loose yarn fragments than the large, sweater-like protein structures most drugs reliably target. As a result, many scientists had written it off as an undruggable molecule.

By defining those relatively rare, stable RNA structures, and then matching those forms to a database he built of complementary small-molecule drugs, Disney built a system for identifying RNA drugs for multiple diseases.

His system has identified compounds now under study as potential disease-modifying treatments for conditions including Fragile X syndrome, muscular dystrophy and inherited ALS.

Beyond ALS and muscular dystrophy, Disney's RNA-modifying tools are showing great applicability to cancers and a variety of other rare genetic disorders, Disney says.

In addition, because many viruses are made of RNA, Disney's technology can be used to identify new classes of antiviral drugs. His team is now developing drug candidates to attack the novel coronavirus, SARS-CoV-2, the cause of pandemic COVID-19.

"Often times viruses, including coronavirus, have specific folds in their RNA that allow them to integrate with the host's protein manufacturing machinery to replicate," Disney says. "We're designing small molecules that target these structures in the RNA to short-circuit this process and serve as lead therapeutics. In principle this could be scaled to every seasonal viral outbreak we're going to be challenged with."

A founder of Expansion Therapeutics in San Diego, Calif. and Jupiter, Florida, Disney has also been recognized with the 2019 Raymond and Beverly Sackler International Prize in Chemistry from Tel Aviv University, the 2018 Weaver H. Gaines BioFlorida Entrepreneur of the Year award, and the 2015 National Institutes of Health Director's Pioneer Award.