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

Nanomedicine. 2019 Oct:21:102067. doi: 10.1016/j.nano.2019.102067. Epub 2019 Jul 23.

Abstract

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.

Keywords: Iron oxide(2); Maternal autoantibody-related autism(1); Peptide-functionalized(4); nanoparticles(3).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / blood
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / immunology
  • Autistic Disorder / pathology
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Disease Models, Animal
  • Female
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • RAW 264.7 Cells

Substances

  • Autoantibodies
  • Peptides