It’s an exciting time for breakthroughs in Duchenne muscular dystrophy (DMD).
On August 10, 2023, a federal advisory committee voted to recommend adding Duchenne to a list of rare disorders for which newborns should be screened. The decision brings the disease one step closer to making it onto the Recommended Uniform Screening Panel (RUSP)—an effort that’s been years in the making.
Only 4 days earlier, Gideon Griffiths, 5, became one of the first boys with Duchenne to receive an infusion of Sarepta’s delandistrogene moxeparvovec (Elevidys) since its June 22, 2023, approval by the US Food and Drug Administration (FDA) for ambulatory 4- and 5-year-old patients. The recombinant gene therapy delivers into the body a gene that triggers the production of microdystrophin—a protein crucial to normal muscle function.
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Gideon got the $3.2 million, one-time treatment from doctors in the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, which invented and tested it.
“This is a meaningful day not only for these first families, but for families battling DMD everywhere,” Jerry Mendell, MD, the center’s principal investigator, said in a press release. “It is thrilling to arrive at this moment of getting treatment to a patient population that has waited so long for more hope.”
However, there’s still a long way to go, said Kevin M. Flanigan, MD, a pediatric neurologist and director of the gene therapy center.
“This is of course a landmark, and we’re very proud to have dosed the first commercial patient,” Dr. Flanigan told Rare Disease Advisor. “But we understand that not all boys with DMD can benefit from this therapy, so among our next challenges is moving from microdystrophin to full-length dystrophin.”
That would mean the world to Tim and Laura Revell of Austin, Texas. Both spoke at this year’s CureDuchenne Futures conference in San Diego, California.
Their sons, Timothy, 19, and Andrew, 16, both have DMD. Timothy was diagnosed in 2005, and Andrew in 2011—and they both have duplication of exons 53 through 57. Realizing nobody was helping them and that they had to raise money for research, the Revells turned to sports—and to Mack Brown, legendary former head football coach of the beloved University of Texas (UT) Longhorns.
“Football is king in Texas, and Coach Brown was very charismatic,” said Tim Revell, 49, who, like his wife, graduated from UT and had started a fundraiser with the UT Golf Club. The Longhorns football team had played in the 2009 National Championship game, and there was “a lot of hype and visibility,” he said.
“We were looking for people who had a faith-minded approach to raising money for Duchenne. Faith grounds us, and it’s the breath of who we are,” he said, adding that the UT Golf Club fundraiser was soon renamed the Champions to CureDuchenne Gala.
Added Laura Revell, 54: “My husband is a marathon runner, so we started running to raise money for Duchenne research. The first time, we raised $15,000, but that wasn’t enough. It takes $1 million to fund the beginning of a research project.”
Tim Revell didn’t give up. Since then, he has run the annual Austin Marathon 18 times, raising more than $300,000 for CureDuchenne, which has been one of the marathon’s founding benefactor charities since 2004.
“They have one of the most difficult mutations to work with, yet the Revells have been one of the most active families in the entire Duchenne community, engaging with other families and raising millions of dollars,” Debra Miller, CureDuchenne’s founder and CEO. “This is the very definition of grit.”
About $1.1 million of that has gone to finance Dr. Flanigan’s work at Nationwide Children’s over a 10-year period.
“We were the only organization to fund his early work,” Miller said. “The first grant enabled him to create a new mouse model that had a duplication mutation. The second grant paid for his [Investigational New Drug] enabling work, and the third helped him do the work necessary to start a clinical trial.”
Biotech firm Locanabio is already using an approach similar to that being studied by Dr. Flanigan. The San Diego-based biotech is working on a small nuclear RNA (snRNA) molecule that could benefit DMD patients who are amenable to exon 51 skipping. Intramuscular injection of Locanabio’s investigational therapy, LBIO-115, led to greater than 80% exon skipping in skeletal muscle, with more than half of muscle fibers positive for dystrophin protein after only 4 weeks, according to data presented by Ranjan Batra, PhD, the company’s senior vice president of research and development, at CureDuchenne Futures.
“For years, we’ve been interested in getting the full-length dystrophin as opposed to the microdystrophin,” Dr. Flanigan explained. “A sizeable number of patients have everything they need to be able to express full-length dystrophin, if you could properly splice it.”
He continued: “An example would be patients with duplications, and the most common is a duplication of exon 2, which accounts for only 1% of all DMD patients but 10% of all patients with duplications. We were interested in trying to skip exon 2 in a way that allows expression of the fully functional protein.”
While Dr. Flanigan continues his research, the Revells continue to raise money—at this point more than $8 million—through golf tournaments and other events such as the Mack, Jack & McConaughey (MJ&M) concert in Austin, organized annually by Brown, Academy Award-winning actor Matthew McConaughey, and country music singer Jack Ingram.
This year’s MJ&M festival, held April 27-28, 2023, featured Garth Brooks and generated more than $1 million for CureDuchenne research.
Yet there have been disappointments along the way for the Revells. Timothy Revell was in a Fibrogen clinical trial to improve upper-body and pulmonary function, his mother said, “but we took him out because we needed a 6-month washout period to qualify for the Sarepta nonambulatory trial.”
In the end, he didn’t qualify—but the Revell boys do not give up so easily.
“They have Duchenne, but they’re so alive it’s incredible,” Tim Revell said of his sons. “Andrew’s frustrated with it, more so than Timothy, who’s having a hard time using his upper body. His lower body is depleted, and his heart is slowing. He has scarring. Gene therapy would be great for his cardiac function. If we could save his heart, we could save his life.”
