Anti-NRG3 monoclonal antibody, clone FQS5834

Purpose: Array comparative genomic hybridization is available for the evaluation of autism spectrum disorders. The diagnostic yield of testing is 5-18% in children with developmental disabilities, including autism spectrum disorders and multiple congenital anomalies. The yield of array comparative genomic hybridization in the adult autism spectrum disorder population is unknown. Methods: We performed a retrospective chart review for 40 consecutive patients referred for genetic evaluation of autism from July 2009 through April 2012. Four pediatric patients were excluded. Medical history and prior testing were reviewed. Clinical genetic evaluation and testing were offered to all patients. Results: The study population comprised 36 patients (age range 18-45, mean 25.3 years). An autism spectrum disorder diagnosis was confirmed in 34 of 36 patients by medical record review. One patient had had an abnormal karyotype; none had prior array comparative genomic hybridization testing. Of the 23 patients with autism who underwent array comparative genomic hybridization, 2 of 23 (8.7%) had pathogenic or presumed pathogenic abnormalities and 2 of 23 (8.7%) had likely pathogenic copy-number variants. An additional 5 of 23 (22%) of autism patients had variants of uncertain significance without subclassification. Conclusion: Including one patient newly diagnosed with fragile X syndrome, our data showed abnormal or likely pathogenic findings in 5 of 24 (21%) adult autism patients. Genetic reevaluation in adult autism patients is warranted.

Olfactory ensheathing glia (OEG) have been used to improve outcome after experimental spinal cord injury and are being trialed clinically. Their rapid proliferation in vitro is essential to optimize clinical application, with neuregulins (NRG) being potential mitogens. We examined the effects of NRG-1 beta, NRG-2 alpha, and NRG3 on proliferation of p75-immunopurified adult OEG. OEG were grown in serum-containing medium with added bovine pituitary extract and forskolin (added mitogens) or in serum-containing medium (no added mitogens). Cultures were switched to chemically defined medium (no added mitogens or serum), NRG added and OEG proliferation assayed using BrdU. OEG grown initially with added mitogens were not responsive to added NRGs and pre-exposure to forskolin and pituitary extract increased basal proliferation rates so that OEG no longer responded to added NRG. However, NRG promoted proliferation but only if cells were initially grown in mitogen-free medium. Primary OEG express ErbB2, ErbB3, and small levels of ErbB4 receptors; functional blocking indicates that ErbB2 and ErbB3 are the main NRG receptors utilized in the presence of NRG-1 beta. The long-term stimulation of OEG proliferation by initial culture conditions raises the possibility of manipulating OEG before therapeutic transplantation. (c) 2007 Wiley-Liss, Inc.