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

Autor: Elizabeth Edmiston, Andy Lam, Jamal S. Lewis, Rian Harriman, Amir Bolandparvaz, Alexandra Navrotsky, Kristina Lilova, Kenneth Alvarez, Natalia Vapniarsky, Judy Van de Water, Zexi Zang
Rok vydání: 2019
Předmět:
Male
Technology
Autism
In vitro cytotoxicity
Pharmaceutical Science
Medicine (miscellaneous)
Peptide
Iron oxide(2)
02 engineering and technology
Pharmacology
Maternal blood
Mice
Peptide-functionalized(4)
Nanotechnology
2.1 Biological and endogenous factors
Macrophage
General Materials Science
Aetiology
chemistry.chemical_classification
0303 health sciences
Biological Sciences
021001 nanoscience & nanotechnology
Mental Health
Molecular Medicine
Female
0210 nano-technology
Maternal autoantibody-related autism(1)
Intellectual and Developmental Disabilities (IDD)
Biomedical Engineering
Bioengineering
Autoimmune Disease
Article
03 medical and health sciences
PEG ratio
medicine
Animals
Humans
Nanoscience & Nanotechnology
Autistic Disorder
030304 developmental biology
Autoantibodies
nanoparticles(3)
Animal
Macrophages
Autoantibody
medicine.disease
In vitro
Brain Disorders
Disease Models
Animal
RAW 264.7 Cells
chemistry
Disease Models
Chemical Sciences
Nanoparticles
Peptides
Zdroj: Nanomedicine
ISSN: 1549-9642
Popis: Introduction: Autism Spectrum Disorder (ASD) comprises a range of developmental disorders diagnosed in early childhood, where their ability to communicate and interact are impaired. In the U.S., an estimated 1 in 59 children1 is born with ASD and the economic burden is a staggering $268 billion per year2. Current therapies are post-symptomatic and include behavioral interventions or symptom-derived pharmacological treatments. Recently, the Van De Water group discovered that about a quarter of ASD cases are caused by maternal autoantibodies (autoAbs) that can hinder normal neurodevelopment in the fetus. Moreover, they elucidated the seven proteins targeted by these autoAbs in the fetal brain, including lactate dehydrogenase A and B (LDHA, LDHB)3. Herein, we aim to develop a System for Nanoparticle-based Autoantibody Retention and Entrapment (SNARE) prophylactic as a biomagnetic trap-for sequestration of disease-propagating Maternal Autoantibody-Related (MAR) autoAbs. Our central hypothesis is that upon intravenous injection, the iron oxide NPs surface-conjugated with autoantigens will circulate throughout the maternal vasculature, and specifically ligate MAR autoAbs, thereby limiting antibody (Ab) transport across the placenta and preventing MAR autism. Currently, investigative aims are to synthesize SNAREs, assess Ab binding capacity, cytotoxicity and immunogenicity in vitro, as well as determine in vivo distribution and maximum tolerated dose.
Databáze: OpenAIRE
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