The National Institute of Neurological Disorders and Stroke, (NINDS) part of the National Institutes of Health (NIH) in recognition of high-impact work advancing the field of RNA-targeting medicines, awarded a $11 million research grant to a Scripps Research Institute investigator to study brain diseases as well as the virus behind the COVID-19 pandemic. Leading a 25-person lab, Matthew Disney, PhD, a chemistry professor with the Jupiter, Florida-based research organization, takes on challenging diseases such as Alzheimer’s disease, ALS, frontotemporal dementia and most recently, COVID-19. Disney’s research focuses on RNA, the single-stranded genetic material associated with cell regulation.
An Elite NINDS Award
Professor Disney just received an incredibly prestigious award as it offers an unusual amount of time and duration for basic research—enabling creative scientists with a proven track record to focus their time and talent on advancing science rather than continuous grant writing to keep the project going. Lasting for up to five years—extendable to eight—Disney’s research can benefit for up to $11 million.
Why did Disney achieve this Award?
Well, according to Douglass Bingham, executive vice president of Scripps Research (Florida), first and foremost this is the second time in four years Scripps Research Institute investigators received this prestigious award. Bingham touted the work of Scripps scientists to be able to accomplish his and emphasized that Disney’s work “…has changed the landscape of what scientists now consider ‘druggable targets,’ and the process reinvigorated research on multiple incurable diseases, including muscular dystrophy, ALS and advanced, metastatic cancer.”
Who was the other Scripps Researcher that received the award?
Ron Davis, PhD, was among the inaugural group of 30 scientists to receive the NINDS Research Program Award. Davis has discovered biological mechanisms underpinning memory and forgetting, while searching for new treatments for neurodegenerative diseases.
What will Disney’s Research Target with the Grant funds?
He will use the Research Program Award to advance new treatments for some of the most challenging brain diseases. Disney noted, “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.” He continued, “They are awaiting development of new approaches that can be advanced into medicines for brain and nervous system diseases, from Alzheimer’s, Parkinson’s and ALS and multiple rare genetic diseases.”
His Research World: RNA—a Tough Place
RNA is built of simple stuff, just four nucleic acids. Under an electron microscope, however, it spears more like loose yarn fragments than the large, sweater-like protein structures most drugs reliably target. Consequently, many scientists had traditionally written this off as an undruggable molecule.
How has Disney Advanced the RNA Research Field?
RNA is essential for life and carries out fundamental duties in the cells. For example, RNA templates genes, builds proteins, and regulates multiple cell activities, including how much of a particular protein gets manufactured from the 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. One of Disney’s major breakthroughs—overcoming significant odds—was the designing of a sort of computational and mathematical decoder.
Disney reports, “Our work has developed new ways in which the RNS’ that directly cause these diseases can be manipulated with chemical probes and in some cases, we can use the body’s own defense system to erase disease-driving RNAs.” He continued, “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 the multiple diseases at once.”
Disney’s RNA Drug Discovery System
Disney defined relatively rare, stable RNA structures and thereafter matched them to a database he built of complementary small-molecule drugs. This helped Disney design an actual system for identifying RNA drugs for multiple diseases. For example, his system has identified compounds now under study as potential disease-modifying treatments for conditions including Fragile X syndrome, muscular dystrophy and inherited ALS.
With an understanding that many viruses are made up of RNA, the technology developed at Scripps can be used to identify new classes of antiviral drugs. For example, Disney’s team is now using this proprietary drug discovery technology to identify drug candidates to attack the novel coronavirus, SARS-CoV-2, the cause of the COVID-19 pandemic.
Disney notes that the RNA in COVID-19 (along with many other viruses) is folded in such a way that it integrates “…with the host’s protein manufacturing machinery to replicate.” He offered, “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.”
Disney understands the magnitude and severity of the current pandemic situation, commenting to a local press recently, “We’re going after coronavirus pretty aggressively.”
Entrepreneur: What is Expansion Therapeutics?
Disney is the founder of Expansion Therapeutics in San Diego, CA and Jupiter, FL. Founded in 2016, Expansion Therapeutics is a drug discovery and development company pursuing the vast potential of small molecule medicines for RNA-mediated diseases. They are initially focusing on expansion repeat disorders, a set of ~30 genetic diseases for which there are no satisfactory therapies.
The company has secured a $55 million Series A investment round led by 5AM Ventures, Kleiner Perkins and including RA Capital Management, Alexandria Venture Investments, Novartis Venture Fund, Sanofi-Genzyme BioVentures.
Disney has been recognized with the 2019 Raymond and Beverly Sackler International Prize in Chemistry from Tel Aviv University, the 2018 Weaver H. Gaines Bio Florida Entrepreneur of the Year Award as well as the 2015 National Institutes of Health Director’s Pioneer Award.
Call to Action: Interested in connecting or partnering with Professor Disney? We include his contact information here.