AMONDYS 45 (Casimersen), a Novel Antisense Phosphorodiamidate Morpholino Oligomer: Clinical Considerations for Treatment in Duchenne Muscular Dystrophy

Authors

Megan E. Vasterling, LSU Health Sciences Center - New OrleansFollow
Rebecca J. Maitski, LSU Health Sciences Center - New OrleansFollow
Brice A. Davis, LSU Health Sciences Center - New OrleansFollow
Julie E. Barnes, LSU Health Sciences Center - New OrleansFollow
Rucha A. Kelkar, Medical University of South Carolina, Charleston, SC
Rachel J. Klapper, Louisiana State University Health Sciences Center, Shreveport, LA
Hirni Patel, Louisiana State University Health Sciences Center, Shreveport, LA
Shahab Ahmadzadeh, Louisiana State University Health Sciences Center, Shreveport, LA
Sahar Shekoohi, Louisiana State University Health Sciences Center, Shreveport, LA
Alan D. Kaye, Louisiana State University Health Sciences Center, Shreveport, LA
Giustino Varrassi, Paolo Procacci Foundation, Rome, ITA

Document Type

Article

Publication Date

12-28-2023

Publication Title

Cureus

Abstract

AMONDYS 45 (casimersen) is an antisense oligonucleotide therapy used to treat Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by a mutation in the DMD gene. Symptoms include progressive muscle weakness, respiratory and cardiac complications, and premature death. Casimersen targets a specific mutation in the DMD gene that results in the absence of dystrophin protein, a key structural component of muscle fibers. While there is currently no cure for DMD, exon-skipping therapy works by restoring the reading frame of the mutated gene, allowing the production of a partially functional dystrophin protein. Clinical trials of casimersen have shown promising results in increasing dystrophin production, as measured by polymerase chain reaction (PCR) droplets when compared to placebo. In a randomized double-blind trial, patients who received casimersen had significantly higher dystrophin levels when compared to those who received placebo. Casimersen therapy is administered through repeated intravenous infusions, although the optimal dosage and duration of treatment are still under investigation. Based on the completed and ongoing clinical trials, casimersen has been well tolerated, with most adverse events being mild and unrelated to casimersen. In 2021, AMONDYS 45 (casimersen) received approval from the US Food and Drug Administration (FDA) for the treatment of Duchene muscular dystrophy in patients with a mutation of the DMD gene that is amenable to exon 45 skipping. These collective findings indicate that casimersen has the potential to elicit functional changes in individuals with DMD, although further studies are necessary to comprehensively evaluate the specific functional improvements. Regardless, the FDA approval and ongoing clinic trials mark a significant milestone in the development of DMD treatments and offer hope for those affected by this debilitating disease.

First Page

e51237

PubMed ID

38283433

Volume

15

Issue

12

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Vasterling, Megan E.; Maitski, Rebecca J.; Davis, Brice A.; Barnes, Julie E.; Kelkar, Rucha A.; Klapper, Rachel J.; Patel, Hirni; Ahmadzadeh, Shahab; Shekoohi, Sahar; Kaye, Alan D.; and Varrassi, Giustino, "AMONDYS 45 (Casimersen), a Novel Antisense Phosphorodiamidate Morpholino Oligomer: Clinical Considerations for Treatment in Duchenne Muscular Dystrophy" (2023). School of Medicine Faculty Publications. 2129.
https://digitalscholar.lsuhsc.edu/som_facpubs/2129