Genetic Disorder :: Promising new approach to treating genetic disorders

New preclinical data published online in the current edition of the journal Nature show that PTC124, an investigational new drug designed to bypass nonsense mutations, was efficacious in a preclinical model of Duchenne muscular dystrophy (DMD).

It is estimated that approximately 13 percent of the cases of DMD are due to nonsense mutations.

PTC Therapeutics, Inc., which discovered and is developing PTC124, has catalogued over 1,800 distinct genetic disorders where nonsense mutations are the cause of the disease in a significant percentage of patients. Nonsense mutations inactivate gene function and are known to cause anywhere from five to 70 percent of the individual cases of most inherited diseases, such as cystic fibrosis (10%) and Hurler’s syndrome (70%).

“We are pleased that the Nature paper offers an opportunity for us to describe our novel approach to regulating post-transcriptional control processes,” said Stuart W. Peltz, Ph.D., President and Chief Executive Officer of PTC Therapeutics. “As these preclinical data demonstrate, the broad potential of PTC124 lies in its specificity and unique mechanism of action, which has the potential to address the underlying cause of a broad range of genetic disorders due to nonsense mutations.”

Dr. Peltz continued, “In addition to the ongoing Phase 2 clinical trials of PTC124 in cystic fibrosis and Duchenne muscular dystrophy, we are evaluating PTC124 in a number of additional genetic disorders.”

Post-transcriptional control processes are the cellular regulatory events that take place after an RNA molecule is copied from DNA. These processes are critical to proper cellular function and provide an opportunity for therapeutic intervention through the modulation of protein levels.

Genetic disorders, such as DMD and cystic fibrosis (CF) are caused by genetic alterations, known as mutations. By targeting a specific type of genetic alteration — nonsense mutations — PTC124 bypasses the defect and leads to the restoration of a functional protein. The Nature paper highlights the data obtained from PTC’s work in a mouse model of DMD in which a nonsense mutation precludes the production of dystrophin. Loss of functional dystrophin, an important muscle protein involved in maintaining the strength of muscle fibers, results in DMD. The data demonstrate that PTC124 allows dystrophin to be made in cells in which it was previously absent, to be delivered to the proper cellular location, and to induce restoration of muscle function. In addition to the studies described in the Nature paper, PTC has demonstrated in preclinical studies that PTC124 restores the presence of the missing protein in CF caused by nonsense mutations. Similar to the effect in DMD, PTC124 induces production of CFTR (the missing protein in CF).

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