Exon 44 skipping therapies represent a promising area in the treatment of Duchenne Muscular Dystrophy (DMD), a genetic disorder characterized by progressive muscle weakness and degeneration. In this article, we will examine exon 44 skipping studies that are still being developed for DMD.
DMD is caused by mutations in the dystrophin gene, which is responsible for producing dystrophin, a protein essential for muscle function. In patients with DMD, the dystrophin gene is often mutated in such a way that the full-length dystrophin protein cannot be produced, leading to muscle damage.
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Future Exon 44 Skipping Therapies
Exon skipping therapies are designed to skip over specific exons (the protein-coding parts of a gene) that contain mutations, allowing the production of a shortened but functional version of dystrophin. In the case of Exon 44 skipping, this therapy specifically targets exon 44 of the dystrophin gene, which is skipped during RNA processing. [Read More: What is exon skipping?]
By skipping exon 44, it is possible to create a truncated form of dystrophin that is still functional enough to help stabilize the muscle cell membrane and reduce muscle degeneration. This is beneficial because even a partial restoration of dystrophin function can have a significant impact on slowing the progression of DMD.
Avidity Biosciences
Delpacibart zotadirsen or del-zota is a treatment designed to treat people with Duchenne muscular dystrophy that is amenable to exon 44 skipping (DMD44).
Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to activate dystrophin production by specifically skipping exon 44 of the dystrophin mRNA.
Del-zota is currently in Phase 1/2 development as part of the EXPLORE44™ trial in people with DMD44. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted del-zota Orphan status. The U.S. Food and Drug Administration (FDA) has granted del-zota Rare Pediatric Disease status and Fast Track status.
Entrada Therapeutics
Among the exon 44 skipping therapies, ENTR-601-44 is an investigational study by Entrada Therapeutics. The study is still in the clinical phase.
Also recently, Entrada Therapeutics receives UK authorization to begin ELEVATE-44-201 (Exon 44 Skipping Treatment), a phase 1/2 multiple ascending dose clinical study of ENTR-601-44 in duchenne muscular dystrophy patients. [Read More: ELEVATE-44-201 Clinical Study]
NS Pharma
Brogidirsen (NS-089) is under development for the treatment of Duchenne muscular dystrophy. It is developed based on exon skipping technology which skips exon 44 of the dystrophin gene. It is administered through parenteral and intravenous route.
Nippon Shinyaku Corporation has announced the first human trial results of its drug ‘Brogidirsen’ (NS-089/NCNP-02), which was developed for exon 44 skipping in the treatment of Duchenne muscular dystrophy (DMD). [Read More: NS-089/NCNP-02 Clinical Trial]
Dyne Therapeutics
Dyne Therapeutics’ research studies, which are in the research phase and are planned to be applied to patients amenable for exon 44 skipping, are being followed all over the world.
While the DYNE-251 study currently being conducted by the company is promising, it is hoped that the exon 44 study could also be successful. [Read More: Dyne Researches]
PepGen
Pepgen is currently working on an exon 44 skipping study it calls PGN-EDO44.
Positive clinical data from the study were announced in 2022. [Read More: PepGen Announces Positive Preclinical Data for PGN-EDO44]
Sarepta Therapeutics
Sarepta, which has brought hope to the whole world with its gene therapy called ELEVIDYS developed for Duchenne muscular dystrophy, continues its exon 44 skipping study in the clinical phase.
Sarepta currently has 3 exon skipping therapies approved by the FDA: Exondys 51, Vyondys 53, and Amondys 45.
Wave Life Sciences
The company currently has a study that may yield positive results regarding exon 53. In addition, it also has a study regarding exon 44 skipping. However, it is still in the research phase.
Conclusion
Recent studies on exon 44 skipping for Duchenne muscular dystrophy (DMD) have shown promising potential in addressing the underlying genetic cause of the disease. By targeting exon 44, these therapies aim to restore the production of a functional dystrophin protein, which is crucial for muscle function. Early-stage clinical trials have demonstrated positive outcomes in terms of safety and efficacy, making exon 44 skipping a hopeful strategy for improving muscle strength and slowing disease progression in DMD patients. As research continues, these therapies may offer a transformative approach to treating this devastating condition.
Learn More: Potential Upcoming New Gene Therapies for Duchenne Muscular Dystrophy
