Looking to the Genome to Address ‘Undruggable’ Diseases including Parkinson’s, ALS, Cancer and More
Biochemist Matthew Disney, Ph.D., has found that many incurable diseases can potentially be cured via key RNA. He’s racing against time to create novel treatments and get them to patients.
Original Thinking Changes the Script for Incurable Diseases
It may seem that conditions such as muscular dystrophy, Parkinson’s and SARS-CoV-2 have nothing in common. But Matthew D. Disney, Ph.D., the Institute Professor and Chair of the Department of Chemistry at The Wertheim UF Scripps Institute, sees things differently. He’s an expert on RNA. What these diseases have in common is that RNA drives progression of the illnesses, Disney explains. His experiments are showing that disease-causing RNA can be targeted in specific and potent ways with medications engineered to stop disease in its tracks.
Understanding The Biology
Much of the human genetic code spells out instructions for making RNA, the worker molecules of the cell. Cells require many different types of RNA to carry out all the tasks necessary for life. There are RNA for reading genes; RNA for moving genetic information throughout the cell; and RNA for building the proteins that make life possible, from hemoglobin to collagen, just to name a few. But if mutations occur, they can cause toxic proteins to be made, resulting in disease.
There was a time when the scientific consensus was that RNA could not be targeted with medications, because of its relatively simple makeup and its structure. Plus, RNA shifts its shape like a noodle, constantly twisting and turning. It exists briefly to do its job, then it is recycled. For these reasons, early in his career, Disney found his ambitions and ideas hitting a wall of skepticism. Disney stayed with it, and has proved repeatedly that treating RNA with medicines is not only possible, but an excellent way to target diseases that were proving extremely difficult to treat – so-called “undruggable” diseases.
Changing Science
Today, because of Disney’s early work, most drug companies and many biotechnology firms now pursue RNA as a way to cure disease. This has provided new options for people with serious diseases including spinal muscular atrophy and types of muscular dystrophy, with more on the way.
In recognition of his impact on science and medicine, the University of Florida has established the Center for RNA Genomic Medicine at The Wertheim UF Scripps Institute.
Disney has changed scientific consensus and changed lives by showing that RNA is a viable drug target. He did this by showing first that many exising, older medications work by acting on RNA. He showed that RNA has many valid targets for targeting medications. He invented chemistry techniques to discover these good targets, and then built collections of compounds likely to have activity against the targets. In the process, he helped launch a new industry, focused on winning the war against incurable disease.
Uniquely Qualified
Disney is Institute Professor and Chair of the Department of Chemistry at The Wertheim UF Scripps Institute. He earned his Ph.D. at the University of Rochester and conducted fellowships at the Massachusetts Institute of Technology and the Swiss Federal Institute of Technology in Zurich. In 2010, he moved his lab to Scripps Florida, which joined the University of Florida in 2022.
Disney is a founder of several biotechnology companies, including Smart Therapeutics, Ribonaut Therapeutics and Expansion Therapeutics. He is a recipient of the 2016 National Institutes of Health Director’s Pioneer Award. He was named BioFlorida’s Entrepreneur of the Year. He also won the Sackler International Prize in the Physicial Scienes, Chemical Biology, and the American Chemical Society awarded him and his student, Ali Angelbello, PhD, their Nobel Signiature Award for their work on myotonic dystrophy.
Disney’s studies have provided multiple experimental medications for incurable conditions and viral disease. The list of conditions he is targeting is long and growing: ALS/frontotemporal dementia; hard-to-treat cancers including triple-negative, metastatic breast cancer; glioblastoma, and pancreatic cancer; Parkinson’s; Alzheimer’s; heart disease, and RNA viruses such as SARS-CoV-2.