Role for nongenetic factors in the development of Hirschsprung disease?

摘要

Robert Heuckeroth and colleagues have found that the immunosuppressant mycophenolic acid (MPA) causes a Hirschsprung-like pathology in mouse models of the disease, providing hope that some cases of Hirschsprung disease (HSCR) might be preventable.1 in 5,000 infants are born with HSCR, which is characterized by the absence of the enteric nervous system (ENS) at the end of the bowel (aganglionic bowel). "Although surgical resection of the aganglionic bowel dramatically reduces the risk of death and reduces morbidity, death rates from HSCR in the modern era are about 5%," explains Heuckeroth. Heuckeroth's team investigated the role of nongenetic factors because none of the many genetic defects known to predispose to HSCR are completely penetrant. In addition, his group previously found that GSK3 beta antagonists and vitamin A deficiency slow ENS precursor migration through the bowel. As ENS precursors have a long migratory route and most children with HSCR have only a short region of aganglionic bowel, modest increases in ENS precursor colonization efficiency could prevent this life threatening disease.