REGENXBIO Publishes Preclinical Findings on RGX-202 Gene Therapy for Duchenne Muscular Dystrophy

On July 10, 2025, REGENXBIO Inc. (Nasdaq: RGNX) announced the publication of preclinical results regarding its investigational gene therapy RGX-202, which employs a novel microdystrophin construct designed to treat Duchenne Muscular Dystrophy (DMD). The study, published in the peer-reviewed journal Molecular Therapy Methods and Clinical Development, reveals that the microdystrophin containing a C-terminal (CT) domain demonstrates superior functional benefits compared to its counterpart lacking this domain.

Duchenne Muscular Dystrophy, a severe genetic disorder characterized by progressive muscle degeneration, affects approximately 1 in 3,500 to 5,000 boys born each year globally. The condition is caused by mutations in the dystrophin gene, leading to a deficiency in dystrophin, a key protein necessary for muscle integrity (Miyagishima et al., 2024, *Journal of Genetic Medicine*). The absence of dystrophin results in muscle vulnerability, ultimately leading to the loss of mobility and independence.

The preclinical studies utilized mdx mice, a standard animal model for DMD research, to compare the efficacy of two gene therapy constructs: one featuring the CT domain and one without. Results indicated that the microdystrophin with the CT domain maintained higher protein levels in muscle tissues, recruited dystrophin-associated proteins more effectively, and exhibited increased muscle force and resistance to damage (Danos et al., 2025, *Molecular Therapy Methods and Clinical Development*).

Dr. Olivier Danos, Chief Scientific Officer at REGENXBIO, emphasized the significance of these findings, stating, "We specifically designed RGX-202 differently from other gene therapies with the goal of providing improved outcomes for patients. This research further validates the therapeutic advantage of adding the CT domain, which plays a crucial role in preventing muscle breakdown associated with functional decline in Duchenne."

Further reinforcing this perspective, Dr. Michael Kelly, Chief Scientific Officer of CureDuchenne, remarked, "AAV gene therapy holds great promise for Duchenne, and the community is in need of treatment options that can enhance function and quality of life for patients. The CT domain is a critical part of the dystrophin gene, and these preclinical results highlight its role in muscle health."

The interim results from the Phase I/II AFFINITY DUCHENNE clinical trial of RGX-202, reported in June 2025, demonstrated consistent evidence of positively altering the disease trajectory in Duchenne patients, alongside a favorable safety profile (REGENXBIO, 2025). The pivotal portion of this trial is currently enrolling participants, with plans to submit a Biologics License Application (BLA) via the accelerated approval pathway by mid-2026.

The RGX-202 gene therapy is noteworthy for its differentiated microdystrophin construct, which is designed to closely resemble the naturally occurring dystrophin protein. This construct not only includes the CT domain but also features additional design elements aimed at optimizing gene expression and minimizing immunogenicity (REGENXBIO, 2025). This innovative approach positions RGX-202 as a potential best-in-class therapy, addressing a critical need for effective treatment options in Duchenne.

In summary, the promising preclinical results published by REGENXBIO offer hope for advancing treatment modalities for Duchenne Muscular Dystrophy. The ongoing clinical trials and the unique design of RGX-202 suggest a path towards improving the quality of life for affected individuals. As the medical community eagerly anticipates further findings, the potential for gene therapy to transform DMD treatment remains an area of significant interest.