Matthew Disney, a professor at the Scripps Research Institute in Jupiter, Fla., was awarded an MDA research grant totaling $300,000 over a period of three years to optimize two novel drug-like compounds — one that targets toxic RNA in myotonic dystrophy and another that targets toxic RNA in ALS (amyotrophic lateral sclerosis).
Please describe your current research.
Myotonic dystrophy type 1 (DM1) is a genetic disease characterized by multisystemic wasting of muscle function, including organ wasting that leads to cardiac disease, respiratory impairment, cataracts and a host of other significant problems. Likewise, ALS, aka Lou Gehrig’s disease, is a progressive, degenerative disorder of motor neurons, resulting in muscle atrophy and paralysis. Up to 50 percent of ALS patients also develop abnormalities in behavior, language and personality. Both diseases are caused by a toxic biomolecule. No effective treatment is available for ALS or DM1.
Our work focuses on two compounds, one that ameliorates DM1-associated defects in patient-derived cell lines and a mouse model, and another that improves ALS-associated defects in patient-derived cells and is blood-brain-barrier penetrant (able to pass through the barrier that separates circulating blood from the brain fluid in the central nervous system). We will engender our compounds with the ability to remove the toxic biomolecule from disease-affected cells.
We will also study the selectivity of our compounds in patient-derived cells and mouse models using novel and innovative methods developed by our laboratory. These studies can identify unintended “off-targets,” which could cause side effects. Because any therapeutic for DM1 or ALS would, in principle, be given to a patient for the course of his or her life, these studies and tools to investigate off-targets are critically important.
Collectively, our studies will accelerate treatments for DM1 and ALS patients.
What inspired you to study myotonic dystrophy?
When I was a graduate student at the University of Rochester, Prof. Charles Thornton presented new and exciting data on how RNA causes various forms of muscular dystrophy. Because I was studying RNA and was interested in designing drugs directed against it, I was inspired to think about these RNAs as potential drug targets.
What is your area of focus within the myotonic dystrophy field and why is it important?
My focus is on developing general and rational approaches to design small molecule drugs targeting RNAs that cause disease.
There are no known treatments for these disorders, and RNA is not a traditional target for drugs. We hope to change the view that drugs cannot be made for RNA.
Why is it important that MDA continue to fund research in myotonic dystrophy?
It is a tremendously risky endeavor for anyone to make a drug but especially drug companies who invest billions of dollars to get a drug to market. They are not going to deploy their resources if the risk is too high. My goal is that our studies will “de-risk” such investments and will help contribute to bringing therapies to patients.
What do you feel people impacted by myotonic dystrophy can have the most hope about with respect to research right now?
We are getting closer by the day to a treatment. I know it is a long process, but patients should be more optimistic than ever that a drug will come.
Does your work have any potential implications for other disease fields?
Yes, our work can broadly impact the development of drugs to treat diseases that are mediated by RNA. This includes — in addition to ALS and myotonic dystrophy — fragile X syndrome, Huntington’s disease and various ataxias, including spinocerebellar ataxia, to name a few.
To learn more about how you can unite with MDA to end myotonic dystrophy, please visit mda.org.