Three ambitious pilot programs—being conducted in New York, Massachusetts, and North Carolina—are testing the feasibility of widespread screening of newborns for Duchenne muscular dystrophy (DMD).
All 3 programs analyze a small amount of blood collected from a prick of an infant’s heel within 24 to 48 hours of birth, testing the concentration of the creatine kinase MM (CK-MM) protein. Elevated levels of CK-MM may indicate the presence of Duchenne.
Encouraging Early Results
The first program, conducted by the nonprofit organization Parent Project Muscular Dystrophy (PPMD), involves 9 birthing hospitals in the New York City area. As of September 30, 2021—the end of a 2-year recruitment period—some 36,000 babies had been screened. Of that total, 42 babies were referred to doctors because their blood showed significantly elevated CK-MM levels.
“We don’t have complete and final results yet, but so far, we’ve found 4 boys with Duchenne or Becker muscular dystrophy, as well as one baby girl who’s a carrier,” Niki Armstrong, PPMD’s director of community research and genetic services, told Rare Disease Advisor by phone.
PPMD conducted the pilot in coordination with the National Institutes of Health and the New York State Department of Health. It was supported by a consortium that included PerkinElmer, Pfizer, PTC Therapeutics, Sarepta Therapeutics, Solid Biosciences, and Wave Life Sciences.
“The results are very consistent with the population data we have thus far. We feel like the screen itself worked very well, and we certainly support being able to do this on a large scale,” said Armstrong, a certified genetic counselor and lead curator of PPMD’s Duchenne Registry.
“This project took literally years to build and get off the ground,” she added. “We were able to proceed throughout the whole pandemic. The fact that COVID happened and yet it was still able to continue is really amazing.”
Separately, the Muscular Dystrophy Association (MDA) is helping fund a similar newborn screening program being conducted by RTI International, a nonprofit organization based at North Carolina’s Research Triangle Park.
The pilot covers 99 of the state’s 100 counties (except for rural Tyrrell County, which has no birthing hospitals). Two years into the 3-year program, about 17,000 newborns have been screened, said Paul Melmeyer, MDA’s vice president of public policy and advocacy.
The MDA is funding about $200,000 toward the pilot, with the idea that if successful, it will strengthen the case for adding Duchenne to the Recommended Uniform Screening Panel (RUSP). This list, developed by the US Department of Health and Human Services, includes a range of life-threatening inherited disorders for which treatments exist. Although the list is standardized, states themselves ultimately determine what disorders their own programs will screen for, based on their individual needs and capacities.
“From preliminary results, it appears that one case of DMD was detected through this program, as well as several positive findings for other muscular dystrophies,” Melmeyer said. “Consequently, we’re collecting lots of great data that will potentially provide evidence to nominate Duchenne [for inclusion] in the RUSP.”
In a third initiative, the nonprofit group CureDuchenne has launched a supplemental newborn screening program at Brigham and Women’s Hospital in Boston, Massachusetts. The program is ongoing; no results have been released yet.
“We want to ensure that all babies have the healthiest future possible, and screening for diseases for which early intervention may improve outcome . . . is key to that mission,” said Richard Parad, MD, director of the hospital’s Newborn Genomic Medicine Program, in a July 22, 2021, press release. “Universally available newborn screening is also nondiscriminatory, ensuring a positive impact on health disparities given every baby can be screened at no cost to families.”
The Importance of Early Diagnosis
Debra Miller, founder and CEO of CureDuchenne, said in the press release: “It took our family two long years to receive a proper diagnosis of Duchenne for our son, Hawken. We missed an opportunity to provide the best care possible during that time. Now, with some approved therapies and exciting gene therapies in phase 3 trials, it’s important to catch patients with Duchenne early.”
At the moment, newborn screening for Duchenne is only available on a very limited research basis and is not widespread at all in the United States—or anywhere else, for that matter. The 4 exon-skipping treatments approved to date by the US Food and Drug Administration (FDA) cover roughly 30% of Americans with DMD, though as more FDA-approved treatments come on the market, pressure to include Duchenne on the RUSP is only likely to increase.
In addition, corticosteroids “have traditionally been given after diagnosis, which typically wasn’t until age 4 or 5,” Armstrong said. “But certainly there are questions about whether earlier steroid use could potentially be beneficial. And eventually, gene therapy could potentially be used at an earlier age than current therapies.”
The MDA also hopes to boost federal funding for the newborn screening program from the current $18 million to $30 million, said Melmeyer, adding that the increase is crucial in helping states reach their screening goals.
Pat Furlong, PPMD’s founding president and CEO, called newborn screening “the most effective way to ensure that infants with Duchenne are diagnosed early,” when therapies are likely to be the most beneficial. She noted the existence of 5 approved therapies “and a research pipeline filled with potential therapeutic interventions” to treat DMD.
“Obviously, no one wants their child to be diagnosed with Duchenne, but I am a firm believer that knowledge is power in our fight to end the progression of this deadly disorder,” Furlong said in an October 6, 2021, press release. “Without newborn screening, these families may have spent years on a stressful and exhausting diagnostic odyssey.”