Key result
Treatment with the anti-FcRn monoclonal antibody 4470 during gestation significantly reduced AMC-IgG-induced deformities compared with isotype control in a mouse model.
Why the study?
It was unknown whether blocking FcRn during gestation reduces in utero transfer of pathogenic maternal antibodies and decreases maternal antibody-mediated neonatal disease.
Does FcRn blockade with 4470 reduce maternal-to-fetal transfer of pathogenic antibodies and prevent neurodevelopmental abnormalities in a mouse model of AMC?
Does FcRn blockade with 4470 reduce maternal-to-fetal transfer of pathogenic antibodies and prevent neurodevelopmental abnormalities in a mouse model of AMC?
FcRn blockade during gestation reduces maternal-to-fetal transfer of pathogenic antibodies and prevents neurodevelopmental abnormalities in a mouse model of arthrogryposis multiplex congenita.
Supports preclinical testing of FcRn blockade in maternal antibody syndromes; leaves open human translation.
OBJECTIVE: To determine whether blocking the neonatal Fc receptor (FcRn) during gestation with an anti-FcRn monoclonal antibody (mAb) reduces transfer of pathogenic maternal antibodies in utero and decreases the likelihood of maternal antibody-mediated neonatal disease in the offspring. METHODS: Using a previously established maternal-to-fetal transfer mouse model of arthrogryposis multiplex congenita (AMC), we assessed the effect of 4470, an anti-FcRn mAb, on the transfer of total human immunoglobulin G (IgG) and specific acetylcholine receptor (AChR)-antibodies from mother to fetus, as well as its effect on the prevention of neurodevelopmental abnormalities in the offspring. RESULTS: Offspring of pregnant dams treated with 4470 during gestation showed a substantial reduction in total human IgG and AChR antibody levels compared with those treated with the isotype mAb control. Treatment with 4470 was also associated with a significant reduction in AMC-IgG-induced deformities (limb or spinal curve malformations) when compared with mAb control-exposed embryos and a nonsignificant increase in the percentage of fetuses showing spontaneous movements. 4470 exposure during pregnancy was not associated with changes in general parameters of maternal well-being or fetal development; indeed, male neonates showed faster weight gain and shorter time to reach developmental milestones. CONCLUSIONS: FcRn blockade is a promising therapeutic strategy to prevent the occurrence of AMC and other human maternal autoantibody-related diseases in the offspring.
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Coutinho et al. (2021) studied Arthrogryposis multiplex congenita (AMC). 4470 (anti-FcRn monoclonal antibody) vs. Isotype mAb control was evaluated on Transfer of total human IgG and specific AChR-antibodies, and prevention of neurodevelopmental abnormalities. Treatment with the anti-FcRn monoclonal antibody 4470 during gestation significantly reduced AMC-IgG-induced deformities compared with isotype control in a mouse model.
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