As a genetic disorder characterized by progressive muscle degeneration and weakness, Duchenne muscular dystrophy, or DMD is a virulent form of muscular dystrophy. The absence of dystrophin, which is a protein that helps to keep muscle cells intact, is the cause of this genetic condition. Duchenne muscular dystrophy is one of the nine types of muscular dystrophy, and symptoms typically occur in early childhood for boys. DMD rarely affects girls. The X-linked recessive inheritance pattern is a marker of Duchenne muscular dystrophy, which is always passed on by the mother of the child. This degenerative and aggressive form of muscular dystrophy currently has no cure. However, several APIs are being explored as potential treatment options for this patient population.
Eteplirsen CAS# 1173755-55-9, has recently shown to be a potential opponent against DMD. In a 19-person trial of eteplirsen in the United Kingdom results showed to be promising. Conducted by the UK Medical research Council and sponsored by AVI Biopharma, this trial proved to be safe and tolerable for all patients enrolled. As an exon skipping drug, eteplirsen is currently in development to treat people with Duchenne MD who have these specific deletions in the dystrophin gene. Administered intravenously, eteplirsen is an antisense oligonucleotide designed to keep a section of the dystrophin gene called exon 51 from being included in the final genetic instructions that cells use when making the muscle protein dystrophin. The ultimate goal of exon skipping through the use of eteplirsen is to induce the production of a shortened and partially functional dystrophin protein from the patient’s existing genetic instructions. The success of this small, but efficacious trial has led to a new trial of eteplirsen at the Nationwide Children’s Hospital in Columbus, Ohio.
Drisapersen CAS# 1251830-50-8, has been touted by GlaxoSmithKline and Sarepta as a potential treatment to aid patients with DMD. Results from an early-stage study of drisapersen have been hopeful. Drisapersen is effectual in that it specifically induces exon 51 skipping in the DMD gene. A small, but telling trial of four patients with Duchenne muscular dystrophy offered clinical proof of the effectiveness of drisapersen. In this controlled trial four patients with DMD were administered a single intramuscular 0.8 mg dose of drisapersen. This one dose proved to not only be tolerable and safe, but it also proved to successfully induce exon 51 skipping and dystrophin restoration, up to 35% of normal. The dystrophin restoration was also restored in the majority, up to 94%, of the muscle fibers after the injection. Trials are continuing for the use of drisapersen in treating Duchenne muscular dystrophy in the United States.
Ataluren CAS# 775304-57-9, is a novel drug currently being developed to treat both Duchenne muscular dystrophy and cystic fibrosis. Ataluren specifically targets a gene mutation coined the nonsense mutation. The nonsense mutations have been found to interrupt the production of the CFTR protein, which is a key protein associated with neuromuscular disorders. The nonsense mutations cause the protein to be too short and not function normally. Roughly 10% of patients with cystic fibrosis have been documented to have the nonsense gene. Researchers are hopeful regarding the use of ataluren after a Phase 3 study offered encouraging findings. This Phase 3 study, sponsored by PTC Therapies, involved patients ages six and older with nonsense mutations. Published in June 2012, the results showed that patients who received ataluren throughout the 48 week study had a lower decline in lung function as well as a lower rate of pulmonary exacerbations, as compared with those who took a placebo. While initial studies have focused on patients with cystic fibrosis (CF), continued research and development for the treatment of patients with DMD is underway.
The FDA has already approved the combined drugs sildenafil, spironolactone, and ibuprofen with isosorbide dinitrate to lessen the effects of the disease. This drug combination has already shown great success in pre-clinical studies, and is moving along well in clinical trials.
LGM Pharma provides API eteplirsen, as well as drisapersen and ataluren for research and development purposes. Clients can be assured of continuous support throughout the R&D process, as well as quality API products.
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