 |
Advantages
- Clinically validated in a double-blind phase 2 trial
- Demonstrated significant splicing correction in DM1 patients — a first in this field
Technology Overview & Background
Myotonic dystrophy type 1 (DM1) is the most common type of muscular dystrophy in adults, with a prevalence of 1 in every 2100 births. This devastating disease presents multiple systemic symptoms, including myotonia, progressive muscle weakness, insulin resistance, cardiac conduction defects, and cognitive dysfunction. At present, there is no effective fundamental treatment for DM1.
DM1 is caused by a CTG repeat expansion in the DMPK gene. The resulting mutant RNA accumulates in the nucleus and sequesters splicing regulatory proteins, thereby disrupting normal splicing regulation. This leads to widespread splicing abnormalities across multiple genes, which are believed to underlie the diverse clinical manifestations of the disease. These splicing abnormalities are now recognized both as a central pathogenic mechanism and as biomarkers of disease severity (Nakamori et al., Annals of Neurology, 2013; 74:862–872).
Through a drug repositioning approach, research group identified erythromycin—an established macrolide antibiotic—as a promising therapeutic candidate. We demonstrated its efficacy in DM1 mouse models, showing significant improvements in splicing abnormalities and muscle symptoms (Nakamori et al., Annals of Clinical and Translational Neurology, 2015; 3:42–54).
Subsequently, a Phase 2 clinical trial confirmed the safety of erythromycin in DM1 patients and indicated potential clinical benefit, including improvements in splicing biomarkers. These findings provide a promising therapeutic option for DM1 patients.
However, a major bottleneck for advancing to the next stage is funding. While we plan a one-year Phase 3 trial with around 100 patients—three times the size of the previous study—the availability of sufficient funding remains a major challenge.
Data
- Erythromycin demonstrated favorable safety and tolerability profiles in patients with DM1.
- Significant improvement was observed in the splicing abnormality (CLCN1 splicing biomarker), which underlies myotonic dystrophy, in the erythromycin-treated group (Figure).
 |
Patent and Publication
- PCT/JP2016/070067, Registered in US, GB, DE, FR, CN, JP
- Nakamori et al. eClinicalMedicine, 2023
Principal Investigator & Academic Institution
Prof. Masayuki NAKAMORI (Department of Neurology, Yamaguchi University
Graduate School of Medicine)
Expectations
Partnership Opportunity: The university is seeking a partner to:
- License and lead or support the Phase 3 clinical trial
- Consider joint execution of the Phase 3 study
- Provide financial support (e.g., funding for the Phase 3 trial
Additional Development Possibility:
We also welcome the opportunity to pursue the 505(b)(2) development pathway, including formulation development of long-acting erythromycin to enhance patient adherence—for example, by reducing the risk of unintentional missed doses—and to improve clinical outcomes.
Project ID:TT-01130