This month we are focusing on myotonic dystrophy type 2 (DM2). Country-based studies in western Europe indicate that DM2 prevalence may be on par with DM1, which is assumed to be somewhere between 1:3000 and 1:8000. Because the genetic mutation that causes DM2 was discovered more than ten years after the mutation for DM1, DM2 basic and translational research has lagged behind DM1. Researchers like Dr. Matt Disney are helping to change that.
Matthew Disney, PhD, associate professor in the Department of Chemistry at The Scripps Research Institute in Florida, has been working with a talented research team in his lab on a number of projects, including one studying how small molecules may target toxic RNA folds in DM2. “I became interested in DM2 after the RNA shape that causes the disease was discovered around 2008 or 2009,” Disney says. “I’ve always had an interest in understanding how you can take an RNA sequence and fold it to see how it adapts and is impacted by various drugs.”
Disney began his work on DM working with Dr. Charles Thornton and others at the University of Rochester. “Charles is a wonderful advocate for this disease area and I’m always curious to hear what he has to say,” says Disney.
Disney is optimistic about his current research, noting, "There’s a lot of potential right now because there are a variety of cellular and animal systems being developed to see if the small molecules we’ve designed have therapeutic results. Ultimately, we’ll test these systems on an animal model that’s currently being developed. That’s new and very exciting, particularly because a lot of the strategies for making these drugs could not only help those living with DM2, but could also have a big impact on other orphan diseases.”
Disney points out that although his educational background is in chemistry, his role in the lab has evolved into that of a biochemist. “Essentially, we’re medicinal chemists developing compounds against DM2,” he explains. “Once we’re able to develop these various compounds, we test them to see how well they can reverse disease. At this point, we’re not developing a specific drug, but we’re laying the foundation for pharmaceutical companies that can use the information as a launching point to develop those drugs.”
Because of the important work Disney and his team are doing, the pharmaceutical industry has become very interested in their work. Disney has been asked to speak at a number of pharmaceutical conferences. “I think many of these companies are realizing that they may be able to develop drugs that treat more than just DM2,” he says. “If they can develop treatments for DM2 that can also be used for other disorders—such as DM1, Fragile X Syndrome and Lou Gehrig’s Disease (ALS)—then there’s a much higher interest on their part. The fact that there are a lot of connections being made to treat these other orphan diseases is encouraging and exciting. We’ve also been targeting some RNAs involved in cancer recently—but we always have our home in DM."
The majority of Dr. Disney’s time is spent in the lab or teaching a graduate course in medicinal chemistry at Scripps. “Part of the reason I teach is to stay current and on the forefront of new advances. It helps me focus on the things I should be doing in the lab to try to advance these compounds so we can present a good product,” he explains.
If you would like to hear more about DM2 from Dr. Matt Disney, you can watch his DM2 webinar, presented with Dr. John Day, MD, PhD, of the Stanford University School of Medicine. Dr. Disney and Dr. Day provide an overview of the DM2 disease mechanism and, using this explanation, describe how compounds can be designed as potential therapeutics for this disease.