Chronic anti-phencyclidine monoclonal antibody therapy decreases phencyclidine-induced in utero fetal mortality in pregnant rats

Abstract

Illicit drug use during pregnancy is a serious social and public health problem inflicting an array of deleterious effects on both mother and offspring. We investigated the hypothesis that a murine anti-phencyclidine (PCP) monoclonal antibody (mAb6B5; KD=1.3 nM) can safely protect mother and fetus from PCP-induced adverse health effects in pregnant rats. Pregnant Sprague-Dawley rats (n=4–5) were intravenously administered bolus injections of PCP (1 mg/kg) on multiple days during pregnancy. They were also chronically treated with anti-PCP mAb6B5 at 45 mg/kg as a PCP antagonist. This dose provided one mAb-PCP binding site for every four PCP molecules. Therapeutic and safety study endpoints included pregnancy outcome (litter size, number of live vs. dead pups), maternal hemodynamic status and locomotor activity. Maternal hemodynamic changes (i.e., blood pressure and heart rate) and locomotor activity were measured in dams from gestation days 6–21 (one day antepartum) using a radiotelemetry-tracking device with a femoral arterial pressure catheter. This mAb6B5 treatment regimen significantly (p=0.008) reduced the number of PCP-induced in utero fetal deaths (odds ratio=3.2; 95%CI 1.3 to 7.9) and significantly (p<0.05) reduced acute PCP-induced maternal locomotor effects in the second trimester. Maternal hemodynamic responses to PCP were not significantly affected by mAb6B5 treatment. In conclusion, these data suggest that anti-PCP mAb treatments administered during pregnancy can safely protect a mother and her fetus(es) from PCP-related morbidity and mortality even when the mAb dose is too low to significantly prevent other PCP-induced maternal pharmacological effects.

Treatment with a Monoclonal Antibody against Methamphetamine and Amphetamine Reduces Maternal and Fetal Rat Brain Concentrations in Late Pregnancy

“…This could indicate a slow leakage or transport of mAb4G9 into the fetal compartment. This interpretation is also based on similar studies testing the effects of anti-PCP mAb6B5 on PCP disposition in late-stage pregnant rats and their fetuses (Hubbard et al, 2011a) and results from other studies (Arizono et al, 1994;Nekhayeva et al, 2005).…”

“…Therapeutic and safety endpoints show mAb6B5 treatment produces significant reductions in maternal and fetal PCP brain concentrations. These data also show mAb6B5 treatment does not adversely affect maternal weight gain, pup birth weights, pregnancy outcome, or fetal growth; and, more importantly, mAb6B5 substantially reduces PCPinduced fetal deaths (Hubbard et al, 2011a).…”

A Monoclonal Antibody against 6-Acetylmorphine Protects Female Mice Offspring from Adverse Behavioral Effects Induced by Prenatal Heroin Exposure

“…Passive immunization with anti-6-AM mAb dose dependently reduced heroin-induced psychomotor activation and brain levels of 6-AM and morphine in adult male mice (Bogen et al, 2014;Kvello et al, 2016). While maternal immunization for fetal protection against nicotine, methamphetamine, and phencyclidine has been investigated in rats (Keyler et al, 2003(Keyler et al, , 2005Hubbard et al, 2011a;White et al, 2014), maternal immunization against heroin has not been reported previously. Furthermore, former studies have primarily assessed materno-fetal drug distribution, whereas immunotherapeutic protection against long-term effects of prenatal drug exposure has not been explored.…”