Data Published in Nature May Pave the Way for Improved Therapies For Transplant Rejection, Autoimmune Diseases and Allergy
Thursday February 10, 7:15 am Eastern Time
Company Press Release
SOURCE: Eos Biotechnology, Inc
SOUTH SAN FRANCISCO, Calif., Feb. 10 /PRNewswire/ -- Scientists at Eos Biotechnology, in collaboration with colleagues at Stanford University and the Australian National University, have used genomic technologies to identify genes involved in the processes of regulating the immune system. The data, which appear in the February 10 issue of Nature, provide key clues on how the immune system turns itself on and off. The findings may provide the basis for the future development of more effective drugs to treat autoimmune disorders such as rheumatoid arthritis or to prevent the rejection of transplanted organs.
The cells of the immune system turn a large number of genes on or off in regulating the selective attack of invading organisms, such as viruses and bacteria. At the same time, the immune system avoids attacking normal tissues to which it has developed a "self-tolerance.'' In abnormally functioning immune systems, however, the self-tolerance process can go awry resulting in the body attacking its own tissues or organs. This can result in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and diabetes. The immune system can also mount an unwelcome attack against transplanted organs, resulting in rejection of the donor organ. Currently available treatments for these conditions center around the use of drugs to suppress such unwanted immune responses. These treatments, however, are unable to provide long-lasting restoration of natural self-tolerance and also have unwanted side effects. Drug researchers have long sought ways by which to better mimic the normal process of self-tolerance to aid in the development of drugs with long-lasting and safe therapeutic effects.
In the publication, entitled "How self-tolerance and the immunosuppressive drug FK506 prevent B-cell mitogenesis,'' the authors identify a set of genes that appear to be associated with a normal self-tolerance process. The group used Affymetrix GeneChip® technology and a genetic mouse model to study how the immune system reacts to the same protein seen either as a foreign antigen, when it induces an immune response, or as a self antigen, when it induces a self-tolerance response. This well characterized animal model was developed by co-author Chris Goodnow (formally of Stanford University and now Director of the Medical Genome Centre at ANU). The group studied the levels of thousands of genes potentially turned on and off ("gene expression'') in this model versus the effects on gene expression of FK506 (tacrolimus, PROGRAF®); a widely prescribed drug for the prevention of transplanted organ rejection. Although clinically effective, treatment with FK506 does not provide long-lasting tolerance and exhibits side effects.
Dr. Richard Glynne, lead author of the study and head of the genomics biology group at Eos, comments, "Comparison of gene expression levels in the self-tolerance model versus FK506 treatment indicates that the effects of FK506 are very different from natural self-tolerance at the molecular level. Knowledge of these genes involved in natural self-tolerance may allow the development of a drug screen for more effective therapeutics with fewer side-effects.''
"Traditional methods to study self-tolerance depended on the use of complex animal models, limiting its utility in drug screens. In this approach we have defined gene expression changes as indicators of self-tolerance which can be measured much more easily,'' said Dr. David H. Mack, Ph.D., vice president of genomics research at Eos and senior author of the paper. "This research is an example of how the integration of well characterized models, cutting edge genomics technology and a stringent statistical analysis of the data can provide new insights into basic biology, so important for successful drug discovery and development.''
Eos Biotechnology develops, applies and integrates a variety of high-throughput
genomics, bioinformatics and pathobiological processes for the creation
of novel therapeutic and diagnostic products. Eos technologies are being
applied to rapidly and cost-effectively build a pipeline of novel, medically
important therapeutics and diagnostics in the areas of oncology, angiogenesis
and inflammation, with initial product development efforts focused in the
area of therapeutic antibodies. Further information about Eos and its programs
is available at http://www.eosbiotech.com.
Eos Biotechnology, Inc.
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SOURCE: Eos Biotechnology, Inc.