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Sigma-Aldrich Corporation (SIAL)'s SAGE® Labs and Autism Speaks Expand Collaboration to Develop Rat Models for Translational Autism Research



8/2/2012 9:25:43 AM

ST. LOUIS, August 2, 2012 /PRNewswire/ -- Sigma-Aldrich® Corporation (Nasdaq: SIAL) today announced that Sigma Advanced Genetic Engineering (SAGE) Labs, an initiative of Sigma® Life Science and Autism Speaks®, the nation's largest autism science and advocacy organization, expanded a collaboration 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 demandingand crucially informativecognitive 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 collaborationfor the genes MECP2, NRXN1, CACNA1C, PTEN, and MGLUR5are 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.

In a separate collaboration with The Michael J. Fox Foundation, SAGE Labs created the first animal models of Parkinson's disease that display deficits in movement similar to those developed by humans. Other genetically modified research models created by SAGE Labs include rats for Alzheimer's, schizophrenia, cancer, and cardiovascular disease research, as well as rats for toxicology testing in drug development. SAGE Labs' model generation services are available for rats, rabbits, mice and other organisms.

For more information, visit www.sageresearchmodels.com.

Cautionary Statement: The foregoing release contains forward-looking statements that can be identified by terminology such as "enable," "initial data demonstrates," "predictive," "encourage" or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived there from. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that gene knockout rat models of autism-associated genes or related services will assist the Company to achieve any particular levels of revenue in the future. In particular, management's expectations regarding products associated with gene knockout rat models of autism-associated genes or related services could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; the Company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company's assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich's current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma-Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

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. Autism Speaks is a registered trademark of Autism Speaks, Inc.

SOURCE Sigma-Aldrich Corporation


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