Understanding the Cause and Prevention of Birth Defects: Southern Research’s DART Program Conducts Critical Reproductive Toxicology Work

Birmingham, Ala. — A recent study published in the journal Occupational and Environmental Medicine suggests that men engaged in certain occupations—including mathematicians, office workers and artists—have a greater risk of having children with birth defects. Last month, an Australian woman born without arms and legs after her pregnant mother took an anti-morning sickness drug reached a multimillion settlement with the drug’s distributor. Birmingham-based Southern Research conducts studies that it hopes will lead to a better understanding of why these things happen.

“Clearly, the earlier a connection is made between a new drug or a chemical, and possible resulting birth defects, the better for all concerned,” said Eve Mylchreest, Ph.D., program leader for Developmental and Reproductive Toxicology (DART) at Southern Research. “Most reproductive disorders have unknown etiologies, but there is evidence that environmental factors can be the cause or a contributing factor. Identifying these factors and understanding the mechanisms underlying key processes, including key target molecules, are crucial in preventing reproductive disorders and birth defects.”

Dr. Mylchreest came to Southern Research from Pfizer where she was a principal research scientist in reproductive toxicology. She has 15 years experience as a study director conducting Good Laboratory Practices (GLP) studies for drugs, pesticides and commodity chemicals. Since 2010, Dr. Mylchreest has worked with her Southern Research team to establish a program that investigates potential new drugs and environmental hazards, and determines the systemic impact to future parents and their offspring.

The program — DART — is a key component in Southern Research’s comprehensive toxicology services—providing a range of GLP-compliant specialized assessments that determine a compound’s effects on reproductive functions and developmental outcomes. The program is housed in state-of-the-art laboratories using market leading technologies, such as Instem’s integrated Provantis software system which is used to design and execute diverse study types to determine a compound’s effects on fertility, embryo-fetal development, and pre- and post-natal development.

“Southern Research was one of the first companies to validate its version of the Provantis software,” said John Boycott, Instem’s Product Manager, Reproductive Toxicology. “Because of the repro tox expertise of their scientific team, they created and added more than 50 new endpoints to meet the strenuous demands of DART data reporting.”

Reproductive toxicologists or teratologists at Southern Research use the system to conduct studies including ICH protocols, multigenerational, developmental toxicity, behavioral and development neurotoxicity studies, among others. Their system and process has simplified the management of event driven studies while enabling the technical staff to generate both simple and complex custom reports.

“Reproductive toxicology studies are complex, so the data needs to be reported in a comprehensive and meaningful way to facilitate the interpretation of results. We can now create endpoints that allow us to extract and calculate the precise data we need to evaluate if a compound has adverse effects,” said Dr. Mylchreest. “After all, the ultimate reason for conducting these preclinical studies is to ensure that new drug candidates do not cause harm to unborn children and do not impair the ability to have children.”

Southern Research conducts both contract research and basic research for clients, providing preclinical drug discovery, development, and clinical trial support services in cancer, infectious diseases, and CNS/neurological disease to pharmaceutical and biotechnology companies. Scientists conduct translational science to invent small molecules and advance them from the design stage to the clinic. Services available include medicinal chemistry, molecular biology, biochemistry, high-throughput screening and a full set of in-house GLP development services including toxicology, ADME/PK, animal models, formulations, and bioanalytical services.

About Southern Research

Southern Research Institute is a not-for-profit 501(c)(3) scientific research organization founded in 1941 that conducts preclinical drug discovery and development, advanced engineering research in materials, systems development, and environment and energy research. More than 550 scientific and engineering team members support clients and partners in the pharmaceutical, biotechnology, defense, aerospace, environmental and energy industries. Southern Research is headquartered in Birmingham, Ala., with facilities in Wilsonville, Ala., Frederick, Md., and Durham, NC and offices in Huntsville, Ala., New Orleans, La., and Washington, DC.