Towards a nanoparticle-based prophylactic for maternal autoantibody-related autism

• Published in: Nanomedicine Vol. 21; p. 102067
• Main Authors: Bolandparvaz, Amir, Harriman, Rian, Alvarez, Kenneth, Lilova, Kristina, Zang, Zexi, Lam, Andy, Edmiston, Elizabeth, Navrotsky, Alexandra, Vapniarsky, Natalia, Van De Water, Judy, Lewis, Jamal S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Animals; Autistic Disorder - blood; Autistic Disorder - drug therapy; Autistic Disorder - immunology; Autistic Disorder - pathology; Autoantibodies - blood; Autoantibodies - immunology; Disease Models, Animal; Female; Humans; Iron oxide2; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Male; Maternal autoantibody-related autism1; Mice; Nanoparticles - chemistry; Nanoparticles - therapeutic use; nanoparticles3; Peptide-functionalized4; Peptides - chemistry; Peptides - pharmacology; RAW 264.7 Cells; nanoparticles3; Maternal autoantibody-related autism1; Peptide-functionalized4; Iron oxide2; Maternal autoantibody-related autism; Iron oxide; Peptide-functionalized; nanoparticles
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2019.102067

Recently, the causative agents of Maternal Autoantibody-Related (MAR) autism, pathological autoantibodies and their epitopic targets (e.g. lactate dehydrogenase B [LDH B] peptide), have been identified. Herein, we report on the development of Systems for Nanoparticle-based Autoantibody Reception and Entrapment (SNAREs), which we hypothesized could scavenge disease-propagating MAR autoantibodies from the maternal blood. To demonstrate this functionality, we synthesized 15 nm dextran iron oxide nanoparticles surface-modified with citric acid, methoxy PEG(10 kDa) amine, and LDH B peptide (33.8 μg peptide/cm2). In vitro, we demonstrated significantly lower macrophage uptake for SNAREs compared to control NPs. The hallmark result of this study was the efficacy of the SNAREs to remove 90% of LDH B autoantibody from patient-derived serum. Further, in vitro cytotoxicity testing and a maximal tolerated dose study in mice demonstrated the safety of the SNARE formulation. This work establishes the feasibility of SNAREs as the first-ever prophylactic against MAR autism. Nanoparticle prophylactic against MAR Autism: (A) Autoantigen-coated Dextran Iron Oxide Nanoparticles (DIONPs) formulation are inject intravenously (I.V.). (B) Autoantigen-conjugated DIONPs will ligate MAR auto-Abs in the mother's blood. (C) Clearance of pathological autoantibodies by liver and phagocytes resulting in normal fetal development. [Display omitted]