According to a February 25 press release, Amondys 45 (casimersen), a therapeutic option for patients with Duchenne muscular dystrophy (DMD), recently became FDA-approved. The therapy is specifically designed for patients with a genetic mutation amenable to exon 45 skipping.
Developed by Sarepta Therapeutics (“Sarepta”), Amondys 45 is an antisense oligonucleotide (ASO). In an excerpt published on ScienceDirect, authors describe ASOs as:
small-sized single-stranded nucleic acids and offer some advantage over siRNAs in terms of targeting both nuclear and cytoplasmic located lncRNAs. Based on their sequence homology, ASOs bind to their target RNA sequence inside the cells and bring about gene silencing.
In this case, Amondys 45 binds to exon 45 and causes mRNA processing to skip over it. The therapy utilizes Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) technology to achieve this goal. As the genetic mutations are skipped and excluded, it offers an opportunity for the body to create internally truncated dystrophin. Dystrophin is the protein missing in patients with DMD, which ultimately causes muscle weakness.
Prior studies have shown that Amondys 45 prompted an increase in dystrophin in patients. However, some trials, such as the ESSENCE trial, are still ongoing. Thus, while the drug is approved currently, the status may change based on future trial results. While Amondys 45 is relatively safe and well-tolerated, some side effects include:
- Joint, mouth, ear, and throat pain
- Upper respiratory tract infections
In the past, other ASOs have been shown to be nephrotoxic. As a result, patients and doctors should monitor kidney function following Amondys 45 administration.
Duchenne Muscular Dystrophy (DMD)
DMD gene mutations cause Duchenne muscular dystrophy (DMD), one of nine forms of muscular dystrophy. These mutations cause patients to lack dystrophin, a type of protein which plays a role in muscle health. In short, dystrophin links muscle cells together. When the body is unable to make dystrophin, muscles weaken. Ultimately, DMD can lead to heart and respiratory weakness, as well as quadriplegia. Because it is inherited in an X-linked recessive pattern, most patients with DMD are male. However, in rare cases (1 in 50 million), a female can inherit DMD. Symptoms usually appear in early childhood, often before age six. These include:
- Difficulty walking or moving positions
- Intellectual and developmental delays
- Muscle weakness in the lower extremities that later spreads throughout the body
- Frequent falling or tripping
- Eventual heart or respiratory failure
- Toe-walking or a waddling gait
- Enlarged calves