making muscle wasting history

In about 13 to 15% of all Duchenne patients, the disease is
caused by a nonsense mutation in the dystrophin gene. This type of mutation is a single-point change that results in the introduction of a premature stop codon into the dystrophin mRNA. Such a premature stop codon causes the protein synthesis to shut down prematurely before the new dystrophin is fully assembled. The incomplete dystrophin is too short to fulfil its normal function, it is destroyed, and Duchenne muscular dystrophy develops.

PTC Therapeutics, Inc, a company in South Plainfield, New Jersey, has – under the direction of Dr. Langdon Miller – developed a drug, PTC124, which allows the protein- making system in the cell to read through such a premature stop codon in the mRNA, so that the full-length protein can be made. Such a treatment is different from gene therapy or exon skipping. To decide whether a boy with Duchenne muscular dystrophy boy can benefit from PTC124, the presence of a premature stop mutation must be proven by genetic analysis.

In pre-clinical experiments in muscle cultures, dystrophin was produced. In mdx mice, which have a premature stop codon in exon 23 of their dystrophin gene, it was shown that PTC124 induces fulllength dystrophin production, resulting in reduced injury during muscle contraction, and decreases the creatine kinase (CK) activity in the blood. Thus, PTC124 may help the muscle cells to overcome one of the genetic causes of Duchenne muscular dystrophy. PTC124 does not read through normal stop codons which have a different structural environment compared to premature stop codons. Toxicity studies in mice, rats, and dogs with high doses of the drug have shown an acceptable profile for continuing clinical development of the drug.

There are still more clinical trials to be done.