BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: DNA-directed DNA polymerase γ (POLG)

May 21, 2015 7:00 AM UTC

In vitro studies suggest scavenging reactive oxygen species (ROS) and peroxynitrites could help treat Cockayne syndrome, a pediatric genetic disorder characterized by accelerated aging and growth defects. Fibroblasts from Cockayne syndrome patients had lower levels of POLG - a catalytic subunit of mitochondrial DNA polymerase - higher levels of serine proteases, ROS and peroxynitrites, and a higher mitochondrial glycolysis-to-oxidative phosphorylation ratio than fibroblasts from healthy subjects. In the patient-derived cells, a scavenger of ROS and peroxynitrites increased POLG levels and decreased serine protease levels and the glycolysis/oxidative phosphorylation ratio compared with no treatment. Next steps include a clinical trial of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a scavengers of ROS and peroxynitrites, to treat Cockayne syndrome...