Boston, Mass. When pregnant women need medications, there is often concern about possible effects on the fetus. Although some drugs are clearly recognized to cause birth defects (thalidomide being a notorious example), and others are generally recognized as safe, surprisingly little is known about most drugs' level of risk. Researchers in the Children's Hospital Boston Informatics Program (CHIP) have created a preclinical model for predicting a drug's teratogenicity (tendency to cause fetal malformations) based on characterizing the genes that it targets.
The model, described in the March 2011 issue of Reproductive Toxicology (published online in November), used bioinformatics and public databases to profile 619 drugs already assigned to a pregnancy risk class, and whose target genes or proteins are known. For each of the genes targeted, 7426 in all, CHIP investigators Asher Schachter, MD, MMSc, MS, and Isaac Kohane, MD, PhD, crunched databases to identify genes involved in biological processes related to fetal development, looking for telltale search terms like "genesis," "develop," "differentiate" or "growth."
The researchers found that drugs targeting a large proportion of genes associated with fetal development tended to be in the higher risk classes. Based on the developmental gene profile, they created a model that showed 79 percent accuracy in predicting whether a drug would be in Class A (safest) or Class X (known teratogen).
For example, the cholesterol-lowering drugs cerivastatin, lovastatin, pravastatin and fluvastatin are all in Class X. All of these drugs also targeted very high proportions of high-risk genes (98 to 100 percent). The anti-coagulant warfarin, also in Class X, had a proportion of 88 percent.
When Schachter and Kohane applied the model to drugs across all risk classes, the proportion of developmental genes targeted roughly matched the degree of known risk (see graph). However, the model ne
|Contact: Keri Stedman|
Children's Hospital Boston