PTC Therapeutics has been awarded a Fast Track (combined Phase I/II) Small Business Innovation Research (SBIR) Grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIDDK/NIH). This award will support additional pre-clinical development of small molecules developed by PTC's Small Molecule Modulation of Read-Through (SMMRT) program. These compounds promote read-through of nonsense mutations as a treatment for genetic disorders.
Inherited diseases are attributable to mutations in an individual's DNA. A common type of mutation, occurring in 10-30% of the cases of all inherited diseases, leads to the synthesis of an mRNA containing an inappropriate stop codon (a nonsense codon) within its protein coding region. The occurrence of such a premature stop codon causes the synthesis of a truncated protein by arresting translation at the site of the nonsense mutation. PTC has developed compounds that restore synthesis of full-length protein from nonsense-containing mRNA and alleviate the disease state.
"Nonsense mutations are significant causes of numerous well-characterized inherited diseases, including cystic fibrosis, hemophilia, familial hypercholesterolemia, lysosomal storage disorders, Duchenne muscular dystrophy, and Marfan syndrome," commented Ellen Welch, Senior Scientist at PTC and principal investigator of this project. Dr. Welch adds: "It is estimated that approximately one-third of all the cases of Neurofibromatosis Type 1 are caused by nonsense mutations."
"We are honored to receive this SBIR grant," said Stuart Peltz, President and CEO, PTC Therapeutics. "PTC's compounds have been characterized in the mdx mouse model of Duchenne muscular dystrophy and studies demonstrate a substantial increase in full-length protein production. The same compounds have demonstrated efficacy in cell lines from patients with cystic fibrosis. Initial studies indicate that these molecules are orally bioavailable and exhibit an excellent safety profile. By targeting the mutation, not the gene, we believe our compounds will be utilized across all genetic disorders where nonsense mutations are a causative factor."