Autism Speaks and SAGE® Labs Expand Collaboration to Develop Rat Models for Translational Autism Research

Unexpected Gene Functions Shown in Initial Studies

New York, N.Y. (August 2, 2012) – Autism Speaks, the world’s leading autism science and advocacy organization, today announced its expanded collaboration with Sigma Advanced Genetic Engineering (SAGE) Labs, an initiative of Sigma® Life, to develop the first rat models with modified autism associated genes, intended to accelerate discovery and translational autism research.

Expansion of the collaboration follows initial behavioral studies demonstrating that the first two publicly available gene knockout rats, part of the seven rats generated through the collaboration to date, exhibit hallmark characteristics of autism, such as social deficits and repetitive behaviors. Many behavioral characteristics of autism observed in these rats are not seen in other animal models currently used for autism research. SAGE Labs and Autism Speaks now plan to generate additional genetically modified rat models of key autism-associated genes, including CNTNAP2 and MET.

“Autism spectrum disorders are a complex condition with significant unmet medical needs. Although uniquely human, fundamental aspects of the biology underlying autism can be effectively modeled in animals to advance our understanding of cause and enable translation of basic scientific discovery into medical breakthroughs that improve the quality of life for individuals on the spectrum,” says Robert Ring, Ph.D., Vice President of Translational Research at Autism Speaks. “These new autism-relevant rat models have already demonstrated great potential for the field. Our new agreement ensures that additional models will continue to be developed and made available to accelerate progress along the entire translational research continuum, from academia to the pharmaceutical industry.”

“Modeling human conditions in rats, rather than the mice that have come to predominate preclinical studies, enables more predictive studies of complex neurobehavioral conditions. Rats are unique in that they exhibit richer, more human-like social behaviors than mice, juvenile play being one example. The more complex neural circuitry and greater cognitive capacity in rats also enables researchers to complete many of the demanding—and crucially informative—cognitive tests that mice cannot perform. In addition, on a practical level, performing initial studies in rats also provides a direct path for drug development,” says Edward Weinstein, Ph.D., Director of SAGE Labs.

Initial behavioral studies of the gene knockout rats generated by SAGE Labs are being conducted by Richard E. Paylor, Ph.D., Professor at the Baylor College of Medicine. In some cases, behaviors observed in the rat models have differed from existing mouse models. For example, whereas FMR1 knockout mice exhibit elevated social interactions, rats lacking the same gene participate much less in social play and emit fewer ultrasonic squeaks during play sessions than control rats. These types of social impairments, such as reduced verbal and interactive play, more closely parallel social behavior symptoms seen in humans with FMR1 mutations. Rat models lacking functional NLGN3 and FMR1 genes also display other unexpected characteristics, including compulsive chewing on water bottles and wood blocks. Compulsive and repetitive behaviors are core symptoms in individuals with autism spectrum disorders.

“At SAGE Labs we use CompoZr® Zinc Finger Nuclease technology to perform targeted genetic modifications in species previously not amenable to such modifications — be it gene knockout, transgene insertion, point mutations, or conditional gene knockout. We can help researchers and pharmaceutical companies access rats, rabbits and other species that best model a medical condition of interest and provide a direct path for preclinical efficacy and toxicology testing,” says Weinstein.

Currently SAGE Labs publicly provides two rat lines with knockouts of autism-associated FMR1 and NLGN3 genes. The remaining five gene knockout rat lines developed in the original collaboration—for the genes MECP2, NRXN1, CACNA1C, PTEN, and MGLUR5—are expected to be released soon. The CNTNAP2 and MET knockout rat lines to be generated in the expanded collaboration are expected to be available in 2013.

About Autism
Autism is a general term used to describe a group of complex developmental brain disorders – autism spectrum disorders – caused by a combination of genes and environmental influences. These disorders are characterized, in varying degrees, by communication difficulties, social and behavioral challenges, as well as repetitive behaviors. An estimated 1 in 88 children in the U.S. is on the autism spectrum – a 1,000 percent increase in the past 40 years that is only partly explained by improved diagnosis.

About Autism Speaks
Autism Speaks is the world’s leading autism science and advocacy organization. It is dedicated to funding research into the causes, prevention, treatments and a cure for autism; increasing awareness of autism spectrum disorders; and advocating for the needs of individuals with autism and their families. Autism Speaks was founded in February 2005 by Suzanne and Bob Wright, the grandparents of a child with autism. Mr. Wright is the former vice chairman of General Electric and chief executive officer of NBC and NBC Universal. Since its inception, Autism Speaks has committed over $180 million to research and developing innovative resources for families. Each year Walk Now for Autism Speaks events are held in more than 95 cities across North America. To learn more about Autism Speaks, please visit www.autismspeaks.org.

About Sigma Life Science
Sigma Life Science is a Sigma-Aldrich business that represents the Company's leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation. Product areas include biomolecules, genomics and functional genomics, cells and cell-based assays, transgenics, protein assays, stem cell research, epigenetics and custom services/oligonucleotides. Sigma Life Science also provides an extensive range critical bioessentials like biochemicals, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, amino acids and their derivatives, and cell culture media.

About Sigma-Aldrich
Sigma-Aldrich is a leading Life Science and High Technology company whose biochemical, organic chemical products, kits and services are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development, the diagnosis of disease and as key components in pharmaceutical, diagnostics and high technology manufacturing. Sigma-Aldrich customers include more than 1.3 million scientists and technologists in life science companies, university and government institutions, hospitals and industry. The Company operates in 35 countries and has nearly 9,000 employees whose objective is to provide excellent service worldwide. Sigma-Aldrich is committed to accelerating customer success through innovation and leadership in Life Science and High Technology. For more information about Sigma-Aldrich, please visit its website at www.sigma-aldrich.com.

Sigma-Aldrich and Sigma are trademarks of Sigma-Aldrich Co, LLC registered in the US and other countries. CompoZr and SAGE are registered trademarks of Sigma-Aldrich Co. LLC.