Mechanism and Long-Term Outlook of Zeleciment Rosturdirsen in Treating Duchenne Muscular Dystrophy: Doug Kerr, MD, PhD

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"We’re seeing not just a slowing of disease decline, but an actual improvement from baseline. That’s a transformative signal for patients with DMD—evidence of real, functional recovery."

Therapeutic development for Duchenne muscular dystrophy (DMD) has accelerated in recent years, with multiple genetic and exon-skipping strategies emerging to restore dystrophin expression and improve function. While adeno-associated virus (AAV)–based gene therapies have produced limited microdystrophin expression, first generation antisense oligonucleotide (ASO)–based therapies have struggled with effective delivery to skeletal, cardiac, and smooth muscle tissues. This delivery challenge remains a key barrier to achieving meaningful, systemic efficacy in patients with DMD, a progressive neuromuscular disorder that leads to severe disability and early mortality.

Zeleciment rostudirsen (z-rostudirsen; formerly DYNE-251), developed by Dyne Therapeutics, is an investigational phosphorodiamidate morpholino oligomer PMO therapy designed to address this challenge through the company’s FORCE platform, which enables broad tissue penetration by targeting transferrin receptor 1. The therapy is being evaluated in the phase 1/2 DELIVER trial (NCT05524883), a global, placebo-controlled study assessing safety, tolerability, dystrophin restoration, and functional outcomes in patients amenable to exon 51 skipping. To date, data released from the multiple-ascending dose portion of the study resulted in the selection of a registrational dose and regimen of 20 mg/kg of DYNE-251 administered every 4 weeks.

In a recent discussion with NeurologyLive^®, Doug Kerr, MD, PhD, chief medical officer at Dyne Therapeutics, discussed the mechanism and rationale behind DYNE-251 in the treatment of DMD. Throughout the conversation, he spoke on the already announced data for the early- and late-stage cohorts, which showed sustained and clinically meaningful functional improvement, along with robust dystrophin expression. With data expected later this year, Dyne plans to pursue accelerated approval in early 2026, followed by a phase 3 program to further validate long-term outcomes.¹

REFERENCE
1. Dyne Therapeutics Announces FDA Breakthrough Therapy Designation for DYNE-251 in Duchenne Muscular Dystrophy (DMD). News release. Dyne Therapeutics. August 4, 2025. Accessed November 17, 2025. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-fda-breakthrough-therapy-0