Autism Spectrum Disorder (ASD) is a significant medical problem. ASD affects approximately 1% of the population and extracts enormous emotional and financial costs from the afflicted and their families. Despite years of research we understand very little about the molecular triggers of ASD and preventative therapeutics remain elusive. Recently, maternal immune activation has been gaining acceptance as a likely environmental trigger. Indeed, a growing body of evidence suggests that specific brain-reactive antibodies in women may put their in utero child at risk for ASD. To date, the researchers working in this area have focused on the pathologic activity of serum or polyclonal antibodies isolated from the mothers of an ASD child. Spark2Flame, Inc (S2F) has licensed intellectual property from the Diamond laboratory at The Feinstein Institute for Medical Research (Feinstein), who has recently taken this analysis to a new level by cloning individual brain-reactive monoclonal antibodies from mothers of ASD children and demonstrating that, when injected intravenously into pregnant mice, such monoclonal antibodies lead to abnormal brain development and ASD-related behavioral abnormalities in male but not female offspring. This gender preference in mice is especially intriguing in view of the fact that ASD overwhelmingly (nearly 5:1) afflicts male children. Since approximately 10% of mothers of a child with ASD harbor brain-reactive antibodies, we are now poised to use these brain-reactive monoclonal antibodies to advance a commercial ASD diagnostic (and ultimate therapeutic modality) that will identify mothers whose unborn child is at risk for this devastating disorder. The objective of this application is to achieve a realistic proof-of-concept milestone in creating an ASD diagnostic/therapeutic product. We will test our hypothesis and accomplish our objectives of this proposal by pursuing two Specific Aims: 1. Identify those antibodies that alter fetal brain development. 2. Expand the panel of anti-brain monoclonal antibodies obtained from mothers of children with ASD. With the successful completion of these Specific Aims, we will attract further funding from the Federal or private sector. With SBIR Phase 2 funding, we will continue focusing on the ASD diagnostic as well as developing a decoy antigen therapeutic approach based on the antibodies that alter brain development. Such an ASD preventative therapeutic offers the advantage that it will be non-immuno suppressive and can be administered during a circumscribed time window.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by abnormalities in three areas: communication, social interaction and stereotypic behavior. Currently no ASD diagnostic exists and therapeutic treatments are largely restricted to non-medical interventions. Herein, we describe a research program that seeks to advance a commercial ASD diagnostic and matched therapeutic approach.
| Brimberg, L; Mader, S; Jeganathan, V et al. (2016) Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice. Mol Psychiatry 21:1663-1671 |
