Individuals with Duchenne muscular dystrophy have mutations in the gene that makes the protein dystrophin. This gene is the largest gene in the human body, with 79 exons. When there are alterations in these exons and dystrophin production is interrupted, muscle wasting occurs. Many muscles in the body are affected when dystrophin is not available, including muscles that control the skeleton and the heart. The disease is progressive, getting more severe over time, but there are great individual differences in how quickly and severely the disease progresses even between individuals with the same mutation. However, by late childhood or early teen years, most children will require a scooter or wheelchair to assist them. Unfortunately, at this time, Duchenne muscular dystrophy (which occurs about once in every 3500- 5000 births) is still invariably fatal by the early 30’s.
Because this is a recessive, X-linked disease, males are primarily affected, but girls may be carriers or have some symptoms (called manifesting carriers). While Duchenne muscular dystrophy can be passed through generations in families, about one in three cases occurs due to a new mutation.
Research continues to bring new hope to this devastating disease. About 13% of individuals with Duchenne muscular dystrophy have a mutation in exon 51 and can be treated with an oligonucleotide that skips that exon (and therefore the mutation) and allows for more functional dystrophin protein to be made.
Recently the Boston based PepGen got approval for a phase 1 clinical trial in Canada for their treatment candidate PGN-EDO51. The product will be administered by IV into 40 healthy adult males to ascertain safety and tolerability. The first volunteer has already been dosed. The company stated that :
“In preclinical studies PepGen observed that treatment of non-human primates with PGN-EDO51 resulted in greater levels of exon-skipping when compared to the most clinically-advanced peptide-conjugated oligonucleotide therapeutic in head-to-head studies, which could translate to higher levels of dystrophin production in patients. Cross-trial comparisons with publicly-available data also suggested that PGN-EDO51 treatment yields the highest rate of exon 51 skipping reported by any approved therapeutic or known development candidate.”
For more information contact PepGen: [email protected],
To find a genetic counselor contact the National Society of Genetic Counselors at : https://findageneticcounselor.nsgc.org/?reload=timezone
For more information on Duchenne muscular dystrophy contact: Parent Project Muscular Dystrophy : https://www.parentprojectmd.org/
