Clinical Trials Look for Breakthroughs in Neuromuscular Therapies

By Jean Yaeger

Grey Gutierrez has a rare genetic disorder that makes his muscles weak, but he doesn’t let Duchenne muscular dystrophy (DMD) keep him off the playground.

The spunky San Antonio 9-year-old uses a wheelchair at school to get from classroom to classroom so that he can save his strength for recess. It’s a strategy – along with physical therapy and medication – that helps Grey keep up with his friends.  

Grey’s battle against DMD includes another tool: Research. In 2019 he enrolled in a clinical trial at Cook Children’s for a medication under development. That trial failed to achieve its goals and the medication was not brought to market.  Grey recently joined a second research study at Cook Children’s.

Worldwide about 20,000 children like Grey are diagnosed with DMD each year. Their bodies don’t produce a protein called dystrophin, which is needed to form and maintain healthy muscles. The disease causes children as young as age 2 to begin having trouble walking or running.  Eventually their heart muscles and breathing break down. But treatments can slow the symptoms.  

Grey’s mom, Marina Teissere, says their family chooses to participate in research despite the possibility of harmful side effects.

“To get medicine to the market takes years. Grey doesn’t have that much time to wait,” she said. “Our best bet is through these clinical trials to get him the medicine before it’s available elsewhere. This is the only way I believe that these kids can get access to it. Otherwise, it’ll be too late.”

Five neuromuscular studies are currently underway at Cook Children’s under the leadership of Stephanie Acord, M.D. and Warren Marks, M.D. Dr. Acord is director of Neurorehabilitation and medical director for the Neuromuscular Medicine and Muscular Dystrophy Association clinics at the Jane and John Justin Neurosciences Center. Dr. Marks is medical director for Movement Disorders.

“It’s patients like Grey and his family that help medicine and treatments continue to advance,” Dr. Acord said. “Without their participation and support, treatment options become stagnant.”

 Seventy-three patients, including Grey, participated in 2023 in the neuromuscular trials at Cook Children’s.  Additional clinical studies are planned for 2024.

Clinical trials nationwide have led to advances that prolong life expectancy and improve quality of life for people with neuromuscular disorders, Dr. Marks said. When patients meet a study’s selection criteria – including genetics, age and other factors – Cook Children’s wants to give them the option to sign up.

“We are trying very hard to offer the latest therapies that are approved as well as promising new therapies that haven’t been released yet, fully understanding that some of them will never come to fruition,” he said. “We think it’s important to at least offer choices to families.”  

Grey comes to Cook Children’s in Fort Worth twice a year to see the neuromuscular experts, as well as respiratory, cardiology and endocrinology specialists. He’s a big fan of Camp MDA, where he went fishing and made pottery last summer alongside other kids with muscle disorders. DMD tires out his body but not his imagination and curiosity. Here’s his journey.  

Determining the Diagnosis

As a baby, Grey was a little slow to roll over and crawl. He hit other developmental milestones such as talking on time. His parents weren’t worried until the teachers at day care noticed Grey had trouble climbing the playground equipment. He tended to drag his right foot. He tripped and fell easily. 

X-rays didn’t show any skeletal problems. Grey was still a toddler; Marina figured that whatever was going on, he would outgrow it.

But at age 4 came a new concern about bowel movements and constipation. His pediatrician in San Antonio ran blood tests. Grey’s level of a liver enzyme, creatine kinase (CK), was extremely high. Injured muscle cells release CK into the blood, and Grey’s elevated level pointed to DMD.

That suspicion led Grey’s family to neurologists in Houston, where the diagnosis was confirmed. He started physical therapy. Meanwhile, Marina searched online and came across a clinical trial Dr. Marks was heading up at Cook Children’s. Grey joined that 2019 study, which explored a medicine designed to reduce or eliminate the need for steroids in DMD cases.

“He had to take three pills three times a day. We needed to make sure he took the medicine right on time and had a lot of high-fat snacks,” she said. “Grey was a trooper.”

Treatment and Another Trial

After that study ended, Grey kept coming to Fort Worth for follow-up appointments because his parents appreciated how the neurology team cared for him during the yearlong clinical trial. What else impressed Marina? That doctors at Cook Children’s are advocates for research.

For ongoing treatment Dr. Marks put Grey on deflazacort, a corticosteroid that reduced the drastic mood swings caused by a previous prescription. Marina thinks deflazacort has slowed down his progressive muscle weakness.

 “The research says it adds maybe three to five years of additional mobility. We’ll take it,” she said. “It means he gets to be that much more mobile for that much longer.”

These days Grey does physical therapy in the gym and swimming pool, along with occupational therapy and recreational therapy through a rehabilitation center in San Antonio. He’s a third-grader with a passion for science, art and animals. Ask him about Camp MDA, and he’ll tell you “it was really fun.” His heart remains strong, and he doesn’t use breathing devices, although it’s tough to cough when he gets sick.

In 2023 Grey started a second clinical study at Cook Children’s. This one analyzes a new medication that aims to preserve and regenerate muscle strength. His parents talked to him about the possible pros and cons. Grey was in favor because he wants more ability to run and less time in the wheelchair.

“It’s taking a risk. But I just think we take that risk, or we do nothing and then it’s too late,” Marina said. “We make sure he knows what’s happening. We make sure that he’s aware of what he’s taking and what it could potentially do or potentially not do, and he seems to be OK.”

More about DMD

Cook Children’s sees about 75 boys with DMD, some from out of state. If a child is toe walking, the family might have consulted an orthopedist first before being referred to neurology for DMD testing. Early diagnosis is helpful, Dr. Marks said.

He applauds the work done by the neuromuscular team at Cook Children’s, which consists of Dr. Acord and Dr. Marks along with Brittney Rhem, M.D.; Marcie Baldwin, RN CPNP; coordinator Megan Batts, RN; Angela Pomykal, PT; and Lindsay Luker, PT at the Motion Analysis Lab.

A new approach to treating DMD became available in June 2023 when the U.S. Food and Drug Administration approved a gene therapy called Elevidys for patients ages 4-5 years old. CRISPR technologies to modify DNA are also being explored. Dr. Marks wants parents to know that treatments will continue to improve as research unlocks the mysteries of neuromuscular disorders.

“When I first started with MDA several decades ago, the messaging was 'The cure’s around the corner.’ The mantra became ‘We just need to keep you stronger until the next thing comes along,’” Dr. Marks said. “Now the cure is closer.”