VAL-0411 is a fusion protein of the proprietary delivery antibody 3E10 linked to an oligonucleotide, which can be used to correct mRNA splicing defect in patients with myotonic dystrophy.
Myotonic dystrophy is the most prevalent adult muscular dystrophy. It is an autosomal dominant, multi-systemic disorder affecting both smooth and skeletal muscles along with other systems. It is a slowly progressive disease beginning in childhood with proximal muscle impairment and multi-systemic complications. Myotonic Dystrophy is divided into two key types – DM1 (98% of patients) and DM2 (2% of patients). DM1 is also divided into 3 subtypes: mild, classic and congenital. The prevalence of this disorder is 1 : 8,000.
DM1 is caused by an abnormality in the DMPK gene. Affected individuals have an increased number of copies of CTG which results in a sequester of muscleblind protein (MBNL1). This protein is an mRNA splicing factor that removes fetal exons from mRNA templates. The inactivation of MBNL1 results in the inappropriate expression of sometimes defective fetal proteins in adult tissues. The greater the number of repeated copies of CTG, the more severe the disease.
Although there are therapies being developed for myotonic dystrophy, none are currently approved.
Early studies in a murine model of myotonic dystrophy have shown correction of mRNA splicing within 4 hours following treatment with VAL-0411.