The Value of Newborn Screening for DMD: Barry Byrne, MD, PhD

Barry Byrne, MD, PhD, pediatric cardiologist and director of the Powell Gene Therapy Center at the University of Florida, discusses considerations when administering gene therapies to pediatric patients and how newborn screening can influence outcomes for patients with Duchenne muscular dystrophy (DMD).

This transcript was lightly edited; captions were auto-generated.

Transcript

Are there unique considerations that must be taken into account when administering gene therapies to pediatric patients?

Our observations in clinical gene therapy as it relates to cardiopulmonary function confirm that in the setting of more advanced cardiomyopathy, like might be present in adults with Duchenne or in later-stage patients with conditions that affect both heart function and neurological function, like in Friedreich ataxia, we have to be mindful of the potential for inflammation in heart muscle cells that can be the result of the gene therapy treatment, and there are safety measures we follow to carefully monitor for those events in the first few weeks after gene therapy. Since the exposure to the heart muscle, like the rest of the musculature, is very high with AAV [adeno-associated virus]–mediated gene therapy, we also have to consider what might be the consequence of expression of a gene product that is not represented in the background of the given patient receiving the treatment, and there can be myocardial inflammation related to that. That's something we usually see after a month following the initial gene therapy. There's no difference in these events in pediatric or adult patients, so we take the same precautions and use the same continuous monitoring approach in all age groups.

DMD is not included in mandatory newborn screening in the US. Can you speak to how newborn screening can influence outcomes in DMD, particularly as gene therapies have become available?

The value of newborn screening as it relates to early detection of DMD, there's several aspects of it that have to be considered. One is that many patients are presymptomatic—or at least, the average age of detection from where there's sufficient separation from their peers is about 4 and a half years of age. When the mother is a carrier of a DMD mutation, if their older son is entering kindergarten or is [aged] 4 or 4 and a half, they may have had another child already, and so any males that are born subsequently to maternal carriers have the same increased risk of Duchenne as the initial sibling. [Therefore,] one consideration is this may help families in family planning.

Of course, there's also the notion that earlier treatment has potential for greater benefit, as is the case with most genetically defined diseases that are progressive or degenerative. Right now, we don't have any evidence that early treatment with the gene therapy product will be more effective, unless there's anticipation that the effect will be sustained over the lifespan, because as we grow, the muscle cells continue to divide and contribute to the ongoing repair of the muscle in Duchenne. And those repair cells, those ones that are responsible for regeneration of muscle, have not been corrected by the gene therapy vector, and therefore, over time, they would lessen the effect. And so there really is an urgent need in the case of early detection of Duchenne to consider how these patients will receive future treatment and sustain the effect over the lifespan.