Methamphetamine (METH) and phencyclidine (PCP) are dangerous drugs of abuse. To address this problem, the PI's team designed and tested anti-drug monoclonal antibody (mAb) medications for treating adverse health effects caused by PCP and METH. Preclinical studies in male rats show that a single dose of the anti-PCP mAb can provide long-lasting neuroprotection, prevent adverse health effects, and reduce behavioral effects of PCP. Even so, a particularly vulnerable population is pregnant women and their fetuses. Clinical and pre-clinical data indicate that prenatal drug exposure can cause intrauterine growth retardation, premature birth, and long-term detrimental effects on brain function. Thus, the proposed studies will extend to the protection of the fetus and mother, testing the hypothesis that anti-drug mAbs can reduce maternal and fetal exposure to drugs, and thereby protect them from adverse drug-induced health effects.
Three aims will be accomplished. 1. Develop an experimental rat model of chronic PCP and METH abuse during pregnancy. 2. Assess the pharmacokinetic profile and safety of anti-drug mAbs in pregnant rats. 3. Determine the ability of anti-drug mAbs to protect the maternal-fetal unit against adverse drug effects during fetal development. Protection by anti-drug mAb is based on its ability to act as a pharmacokinetic antagonist, i.e., removing and preventing the drug from reaching its site(s) of action. Thus, the goal is to first clearly understand the pharmacology of the drugs and mAb in the mother and fetus and then determine how mAb pharmacokinetic antagonists attenuate these effects. These highly integrated studies of pharmacokinetic, pharmacodynamic, and health changes in chronically dosed pregnant rats will serve as a prototypic system to acquire knowledge that can be applied to understanding the vulnerability of the maternal-fetal unit to chronic drug exposure. If successful, these studies could be the first step toward an exciting and innovative approach to improving the health and well being of human pregnant women who abuse drugs, and an important breakthrough in protection for their highly vulnerable developing fetuses.
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