The therapeutic landscape for muscular dystrophy continues to evolve, with emerging approaches moving beyond traditional supportive care and toward treatments designed to address underlying disease mechanisms. Advances in targeted RNA therapeutics, muscle-directed delivery, cell therapy, and molecular approaches aimed at disease-specific drivers have expanded the number of potential treatment strategies under investigation across various neuromuscular disorders. These include therapies for Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and facioscapulohumeral muscular dystrophy (FSHD).

As several investigational agents progress through clinical development, researchers are increasingly focused not only on whether these therapies can modify the underlying biology of muscular dystrophy, but also on whether they can translate those effects into meaningful improvements in muscle function, disease progression, and quality of life. In honor of Muscular Dystrophy Awareness Month, held annually in September, NeurologyLive^® shares 8 emerging agents to watch across the muscular dystrophy treatment landscape.

Dyne Submits BLA for Z-Rostudirsen in Exon 51 Skipping Duchenne Muscular Dystrophy

Dyne Therapeutics has submitted a biologics license application (BLA) to the FDA seeking accelerated approval of zeleciment rostudirsen (z-rostudirsen; formerly DYNE-251) for patients with DMD amenable to exon 51 skipping, marking a major regulatory milestone for the investigational exon-skipping therapy.¹

FDA Extends Deramiocel Review for Duchenne Muscular Dystrophy After HOPE-3 Amendment

The FDA has extended the Prescription Drug User Fee Act (PDUFA) target action date for Capricor Therapeutics’ deramiocel, an investigational cell therapy for Duchenne muscular dystrophy (DMD), from August 22 to November 22, 2026.² The 3-month extension follows the agency’s acceptance of additional phase 3 HOPE-3 (NCT05126758) data as a major amendment to the biologics license application (BLA).³

Del-Desiran Fails to Meet Primary Endpoint in Phase 3 HARBOR Trial of Myotonic Dystrophy 1

Novartis announced that the phase 3 HARBOR study (NCT06411288) evaluating investigational delpacibartetedesiran (del-desiran; formerly AOC 1001) in people with myotonic dystrophy type 1 (DM1) did not meet its primary endpoint of video hand opening time (vHOT), a measure of hand myotonia. Novartis confirmed evidence of clinical activity that was observed in secondary endpoints and exploratory analyses, with full study data undergoing further evaluation.⁴

Overviewing Positive Early Data from ACHIEVE Trial of Zeleciment Basivarsen in DM1: Doug Kerr, MD, PhD

NeurologyLive^® sat down with Doug Kerr, MD, PhD, chief medical officer at Dyne Therapeutics, to discuss the ins and outs of the trial, and the early results backing the agent. He spoke about the consistent improvements across measures of myotonia, muscle strength, and CNS function, with sustained gains observed through 12 months. He noted that these data have positioned z-basivarsen as a potential first-in-class therapy for DM1, with phase 3 plans slated for 2026.

FDA Accelerated Approval Open for FSHD Agent Del-Brax, With Newly Initiated Phase 3 Study to Confirm Efficacy

In a number of company updates, Avidity Biosciences announced the FDA’s openness for an accelerated approval for its investigational agent delpacibart braxlosiran (del-brax) as a potential treatment for FSHD. The company has also initiated its phase 3 FORWARD study (NCT07038200), a confirmatory, large-scale trial further testing the agent’s efficacy and safety, that will be used as supportive evidence for a future regulatory submission.⁵

DYNE-302 — FSHD

Developed by Dyne Therapeutics, DYNE-302 is an investigational RNA-based therapy designed to target the underlying molecular driver of FSHD, aberrant expression of the DUX4 gene.⁶ The therapy combines a fragment antibody targeting transferrin receptor 1 (TfR1), which is highly expressed on muscle cells, with a small interfering RNA (siRNA) designed to reduce DUX4 messenger RNA and downstream DUX4 activity.

Preclinical studies demonstrated robust and durable DUX4 suppression along with improvements in muscle structure and function. In July 2026, the FDA cleared Dyne's investigational new drug application for a randomized, placebo-controlled, double-blind, multiple-ascending-dose phase 1 trial in ambulatory adults with FSHD, marking the program's transition into clinical testing.⁷

SRP-1001 (formerly ARO-DUX4) — FSHD

SRP-1001 is an investigational small interfering RNA (siRNA) therapy designed to reduce expression of DUX4, a key driver of FSHD-related muscle degeneration. Originally developed by Arrowhead Pharmaceuticals as ARO-DUX4, the program is being advanced by Sarepta Therapeutics and uses an αvβ6 integrin-targeted delivery approach intended to selectively deliver the RNAi therapy to skeletal muscle. The agent is being evaluated in a randomized, placebo-controlled phase 1/2 study assessing safety, tolerability, pharmacokinetics, and pharmacodynamics in adolescents and adults with FSHD1.

In preliminary first-in-human data reported in March 2026, SRP-1001 demonstrated dose-dependent muscle exposure, with delivery to muscle tissue observed, along with reductions in creatine kinase and an acceptable early safety and tolerability profile. Further clinical development is planned to evaluate higher dose levels and better characterize the therapy's potential effects on FSHD.^8,9

PGN-EDODM1 — DM1

PGN-EDODM1 is an investigational peptide-conjugated phosphorodiamidate morpholino oligomer designed to target the toxic CUG repeat RNA underlying DM1. Using PepGen’s enhanced delivery oligonucleotide technology, the therapy is designed to enter skeletal muscle, bind pathogenic DMPK RNA, and release sequestered MBNL1 protein to restore normal RNA splicing. Preclinical studies demonstrated reductions in toxic RNA foci and improvements in mis-splicing and myotonia.^10,11

The agent is being evaluated in the phase 2 FREEDOM2-DM1 study (NCT06667453), with preliminary data from the 5 mg/kg cohort showing favorable tolerability and trends toward improved splicing and video hand-opening time.¹² In August 2026, PepGen announced plans to advance the program to its highest planned dose of 12.5 mg/kg following a Data and Safety Monitoring Board review.¹³

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REFERENCES
1. Dyne Therapeutics Announces Submission of Biologics License Application (BLA) to U.S. FDA for Z-Rostudirsen in Exon 51 Duchenne Muscular Dystrophy (DMD). News release. Dyne Therapeutics. May 26, 2026. Accessed September 11, 2026. https://investors.dyne-tx.com/news-releases/news-release-details/dyne-therapeutics-announces-submission-biologics-license
2. Capricor Therapeutics announces extension of PDUFA target action date as FDA continues review of deramiocel BLA. Capricor Therapeutics. August 24, 2026. Accessed August 24, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/354/capricor-therapeutics-announces-extension-of-pdufa-target
3. McDonald CM, et al. Deramiocel heart-derived cellular therapy in advanced Duchenne muscular dystrophy (HOPE-3): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. Published online July 29, 2026.
4. Novartis provides update on delpacibartetedesiran (del-desiran) Phase III HARBOR study for the treatment of myotonic dystrophy type 1 (DM1). Novartis. News Release. September 8, 2026. Accessed September 11, 2026. https://www.novartis.com/news/media-releases/novartis-provides-update-delpacibart-etedesiran-del-desiran-phase-iii-harbor-study-treatment-myotonic-dystrophy-type-1-dm1
5. Avidity Biosciences Announces the Accelerated Approval Regulatory Pathway in the U.S. is Open for Del-Brax and Initiates the Global, Confirmatory Phase 3 FORWARD™ Study in FSHD. News release. Avidity Biosciences. June 9, 2025. Accessed September 11, 2026. https://www.prnewswire.com/news-releases/avidity-biosciences-announces-the-accelerated-approval-regulatory-pathway-in-the-us-is-open-for-del-brax-and-initiates-the-global-confirmatory-phase-3-forward-study-in-fshd-302476170.html
6. Natoli T, Yoder N, Yao M, et al. The FORCE™ platform achieves robust and durable DUX4 suppression and improves muscle function in facioscapulohumeral muscular dystrophy mouse model. Neuromuscul Disord. 2024;43(suppl 1):104441.361. doi:10.1016/j.nmd.2024.07.370.
7. Dyne Receives FDA Clearance to Start Early-Stage FSHD Clinical Trial. Dyne Therapeutics. July 28, 2026. Accessed September 11, 2026. https://www.dyne-tx.com/early-stage-fshd-clinical-trial/
8. Sarepta Announces First Clinical Data from siRNA Pipeline Targeting FSHD1 and DM1. Sarepta Therapeutics. March 25, 2026. Accessed September 11, 2026. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-announces-first-clinical-data-sirna-pipeline-targeting
9. ClinicalTrials.gov. Study of ARO-DUX4 in Adult and Adolescent Patients With Facioscapulohumeral Muscular Dystrophy Type 1. NCT06131983. Updated February 6, 2026.
10. Holland A, Klein A, Lonkar P, et al. PGN-EDODM1: preclinical data supporting the development of an enhanced delivery oligonucleotide (EDO) for the treatment of myotonic dystrophy type 1 (DM1). Neurology. 2023;100(17 suppl 2):4178. doi:10.1212/WNL.0000000000203804.
111. Gilbert J, Klein A, Lonkar P, et al. Nonclinical data for PGN-EDODM1 demonstrated nuclear delivery, mechanistic and meaningful activity for the potential treatment of DM1. Neuromuscul Disord. 2024;43(suppl 1):104441.515. doi:10.1016/j.nmd.2024.07.524.
12. PepGen Announces Topline Results From Lowest Dose (5 mg/kg) MAD Cohort in the Ongoing Phase 2 FREEDOM2 Study Demonstrating Favorable Safety, Splicing and vHOT Data. PepGen. News Release. March 30, 2026. Accessed September 11, 2026. https://investors.pepgen.com/news-releases/news-release-details/pepgen-announces-topline-results-lowest-dose-5-mgkg-mad-cohort
13. PepGen to Advance PGN-EDODM1 Into Highest Dose Cohort in Phase 2 FREEDOM2-DM1 Study Following DSMB Review. PepGen. News Release. August 6, 2026. Accessed September 11, 2026. https://investors.pepgen.com/news-releases/news-release-details/pepgen-advance-pgn-edodm1-highest-dose-cohort-phase-2-freedom2