The journey to diagnosis and beyond for muscular dystrophy has changed profoundly over the past few years – let alone the past decade. For physicians and patients alike, this change can happen at a dizzying speed.
“Just in the last five to ten years, genetic testing has gotten much more accessible to patients,” said Erin Shehan, a licensed genetic counselor and a Genomic Testing Consultant at PerkinElmer Genomics. “It’s become much more affordable. Insurance is now paying for genetic testing, where in the past, the fear was that patients would get this gigantic bill, and providers were nervous about offering it.”
That means patients are coming into the office much more educated, advocating for themselves and being much more proactive about testing, said Shehan, a sentiment that’s reinforced by a patient’s ability to visit a drug store and get an at-home COVID test, or a chronic or genetic-related health condition and receive results quickly. “Patients really want an answer to a lot of the things that have been happening to them, and physicians need to be prepared for that,” Shehan said.
Fortunately, the rapid advances in technology have made testing more robust with turnaround times measured in days or weeks, instead of months just ten years ago. “The guesswork is now taken out, because you can order a test that’s specific to a certain phenotype or a certain set of clinical features,” said Shehan. “You can order a neuromuscular comprehensive panel. You don’t have to cherry-pick genes, go through the literature, and pick out what you think would make sense. These panels are already curated for you.”
The greater access to better and faster tests has also made a river of genomic data lead into an ocean of choices. The role of the genetic counselors in guiding providers, physicians, and patients has now become more important than ever. “I educate providers on what would make most sense for a patient,” said Shehan, “by taking a very detailed look at the clinical findings of the patient, and their family history.”
For some patients, a whole genome sequencing might be the better way to go instead of a curated panel, said Shehan, because they cast a wider net, and you’re more likely to get answers. Although not all patients necessarily want all the answers. “I think it’s really about comfort level, and about talking to a patient about what they feel comfortable with in terms of the information that will be received,” she noted, because genetic counselors need to discuss the implication of the test for other relatives and family members.
Other patients, however, are actively searching for this information more than previous years, giving genetic counselors a greater role in carrier testing, prenatal testing, and newborn screening.
The genetic counselor also guides physicians and patients to as many options as possible on their diagnostic journey, directing them to resources from Parent Project Muscular Dystrophy (PPMD), the largest nonprofit organization in the US focused entirely on Duchenne and Becker muscular dystrophy, funding research, raising awareness, promoting advocacy, connecting the community, and broadening and expanding treatment options for individuals and family members. Among other services, PPMD offers free genetic testing through its Decode Duchenne Program, funded by several pharmaceutical partners with the sponsored testing performed by PerkinElmer Genomics.
“This program is a really huge win for patients,” said Ann Martin, a certified genetic counselor and the Vice President of Community Research and Genetic Services at PPMD, “to be able to access genetic testing and not have to worry about the cost of the test. Genetic testing to confirm a patient’s diagnosis is more important than ever before because we now have five approved therapies for Duchenne muscular dystrophy, and many exciting treatments in clinical trial now, including gene therapies.”
Martin noted PPMD has been pushing to shift diagnosis earlier and earlier, over a “wait-and-see” or “late bloomer” approach, because the sooner you can get a child to a specialist, the better. “Most of these treatments have to be started early in order to receive the maximum benefits” she said. “Babies are already screened for a lot of genetic conditions at birth, and we’re hoping Duchenne will be added as well. PPMD recently submitted a nomination for Duchenne to be added to the Recommended Uniform Screening Panel. If Duchenne is included with newborn screening, that would really alleviate the long diagnostic odyssey that so many families have to experience and the delay in treatments.”
One of the approved therapies is deflazacort, marketed under the brand name Emflaza®, a corticosteroid which is now standard of care for all boys with Duchenne, to help preserve muscle strength and to keep them ambulatory as long as possible. The other four approved therapies are all exon-skipping therapies that allow cells to “skip” over misaligned sections of genetic code, meaning they’re genetic therapies that are very targeted to a patient’s specific mutation.
“That’s another really important reason to have genetic testing done,” said Martin, “It can really impact your treatment to know what your specific genetic change is and if you qualify for one of these exon-skipping drugs.” Martin noted there are next generation exon-skipping drugs in the pipeline now and some are currently in clinical trials. Researchers and providers are hoping these will be even more effective for some patients or at least provide more choices for patients.
Gene therapy is also an area of great excitement for the Duchenne community. “There are currently several active gene therapy trials for Duchenne. And there are over 40 industries total working in the Duchenne space, so there’s a lot of different treatments being investigated. Some of these are genetic-focused treatments, but others are more focused on the downstream effects, like fibrosis and cardiac issues. I think everyone agrees that in the end, the treatment for Duchenne is really going to be more of a combination approach, treating the heart, treating the fibrosis, and hopefully combining it with one of the genetic therapies. This kind of cocktail approach will likely be what works best.”
With so many changes happening rapidly, Shehan recommends physicians shouldn’t shy away from offering genetic testing. “The thought used to be, if you’re not a genetic counselor, you shouldn’t be offering genetic testing. But right now, the way that reports come back, and all of the resources available, there’s really no need to fear that. The important thing is just ordering the test, and once you get a result, if there’s a question, you can refer the patient out. But just getting the process started, and the earlier the diagnosis, the better.” Martin agrees. “A diagnosis today is so much different than a diagnosis, say, thirty years ago, when there wasn’t a lot to offer patients at that point. We certainly have so much more to offer and can give so much more hope to families now.”