2012 Research

Grant Amount: $20,000

Grant Date: Jan 2012

Research Proposal: To determine the effectiveness of the compound PTC124 (Ataluren) in reading through nonsense mutations in mucolipidosis II (MLII).

Status: Research completed. Please see below for results.

Result: PTC124 is a compound that promotes the "read-through" of DNA nonsense mutations by inserting a random amino acid in place of the premature termination codon, allowing translation to continue until the proper termination codon is reached. Our aim was to treat the fibroblasts of patients with mucolipidosis type II with PTC124 and then measure the activities of several lysosomal enzymes inside the cells as an indirect measurement of GlcNAc-1-phosphotransferase activity. A modest but statistically significant increase in both alpha-fucosidase and beta-glucuronidase activity was observed in cells treated with 20 μM PTC124 compared to untreated cells. However, the results obtained in the first set of experiments were not reproducible, and PTC124 does not appear to have a significant positive effect on lysosomal enzyme activity in fibroblasts harboring a nonsense mutation.