Navigation Links
Model predicts a drug's likelihood of causing birth defects
Date:1/4/2011

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 needs further validation before Schachter is willing to share actual predictions for specific drugs. "We don't want to risk misleading pregnant women from taking necessary medicines," he says.

One difficulty in validating the model is that the "known" teratogenicity it's being tested against often isn't known. Between Class A and Class X are Classes B, C and D, with increasing amounts of risk, but the boundaries between them are based on minimal data. Teratogenic effects may be difficult to spot, since most drugs are taken relatively rarely in pregnancy, some may be taken along with other drugs, and any effects tend to be rare or too subtle to be noted in medical records. Moreover, data from animal testing doesn't necessarily apply to humans.

"A lot of drugs in the middle of the spectrum, and maybe even some in Class A, may cause subtle defects that we haven't detected," says Schachter. "We can't provide a yes/no answer, but we found a pattern that can predict which are riskier."

Given the degree of uncertainty, Schachter and Kohane believe their model may be of interest to drug developers and prescribing physicians, and might provide useful information to incorporate in drug labeling.

"We can now say to patients, 'This drug targets a ton of genes that are involved in developmental processes,'" says Schachter.

Or, conversely, if a young pregnant woman has a heart condition and needs to be treated, physicians may be reassured by a cardiac drug's profile, he adds. "Instead of saying, 'we don't know,' we can now say that the drug is more likely to be safe in pregnancy."

"We have here a prismatic example of the utility of a big-picture, macrobiological approach," says Kohane, director of CHIP. "By combining a comprehensive database of protein targets of drugs and a database of birth defects associated with drugs, we find a promising predictive model of drug risk for birth defects."


'/>"/>

Contact: Keri Stedman
keri.stedman@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related medicine news :

1. Porphyromonas gingivalis accelerates inflammatory atherosclerosis in a mouse model
2. Culturally sensitive treatment model helps bring depressed Chinese immigrants into treatment
3. Mathematical model of the life cycle of red blood cells may predict risk of anemia
4. Hurdles ahead for health care reform primary care model, U-M study shows
5. New 3-D model of RNA core domain of enzyme telomerase may offer clues to cancer, aging
6. Mouse model confirms mutated proteins role in dementia
7. Cholesterol-lowering drug shrinks enlarged prostates in hamster model
8. Virginia Bioinformatics Institute to model immune responses to gut pathogens
9. New Medicare model guidelines for benefit years 2012-2014 in development
10. Disease transmission model says media coverage cuts infection rate and pandemic extent
11. New model may simplify high-dose radiosurgery planning
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/27/2017)... Irvine, CA (PRWEB) , ... March 27, 2017 ... ... company has entered a settlement agreement to resolve the pending litigation between itself ... Court for the District of Utah). , “I am thrilled to announce that ...
(Date:3/26/2017)... , ... March 26, 2017 , ... ... to receive the RealSelf 100 Award, a prestigious award honoring the top influencers ... and to find and connect with doctors and clinics. , In 2016, more ...
(Date:3/24/2017)... ... 24, 2017 , ... Mediaplanet today announces distribution of its ... obstacles facing infection prevention and offer strategies for the health care community to ... , The print component of “Fighting Infection” is distributed within the Friday, March ...
(Date:3/24/2017)... ... 24, 2017 , ... Texas Physical Therapy Specialists (TexPTS) is pleased to ... Road. The clinic is the group’s 7th location in San Antonio and 23rd in ... will provide care from the clinic, which opened March 22, 2017. , ...
(Date:3/24/2017)... ... 24, 2017 , ... As the standards bearer of advanced ... that positions them as the go-to thought leader in all matters concerning oncology ... an always-on, always-fresh news, views and advocacy engine, called ONS Voice. , The ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... -- Research and Markets has announced the addition of ... 2035" report to their offering. ... The Deep Learning: Drug Discovery and Diagnostics Market, ... growing market of deep learning solutions within the healthcare domain. Primarily ... as a novel solution to generate relevant insights from medical data. ...
(Date:3/24/2017)...  GenomeDx Biosciences today announced that six abstracts featuring ... Cancer Classifier tests will be presented at the 32 ... held March 24 to 28, 2017 in ... Europe,s largest urological event showcasing ... field. The abstract titled "Muscle invasive bladder ...
(Date:3/24/2017)... and GENEVA , March 24, 2017 ... Tuberculosis Day revitalizes efforts to develop sutezolid as effective ... World Tuberculosis Day, TB Alliance and the Medicines Patent ... development of sutezolid, an antibiotic drug candidate which demonstrated ... the development of sutezolid in combination with other TB ...
Breaking Medicine Technology: