Mice Model to Aid Discovery of Anti-inflammatory Drugs

Investigators have recently devised a mouse model that exhibits reduced inflammation, which may aid the search for new anti-inflammatory drugs.

The researchers, from Boston University School of Dental Medicine (Boston, MA, USA), discovered that the transcription factor LITAF (lipopolysaccharide [LPS]-induced tumor necrosis factor-[TNF]-alpha factor) controls inflammation through an entirely different pathway than the better-known and evaluated NF-kB transcriptional regulator.

Medications regulating TNF-alpha through the better-known NF-kB pathway such as Remicade, Embrel, and Humira represent a multibillion market. The LITAF transcription factor provides a new approach to treating inflammatory disorders along with other immunologic conditions. The researchers are now offering this in vivo model for sale to further advance the discovery of drugs against inflammatory disorders such as arthritis and Crohn's disease.

In the study, Boston University researchers created a mouse lacking the gene that encodes for the LITAF protein. They found that several cytokines were triggered at lower levels in the LITAF-deficient mice compared with the levels seen in the LITAF-positive control mice. Specifically, the deficient mice were more resistant to the deadly effects of LPS-inducement.

"The generation of the macrophage-specific LITAF-deficient animals opens new opportunities for assessing the role of LITAF in inflammation in hopes of designing anti-LITAF drugs for major inflammatory diseases,” stated Dr. Salomon Amar, from Boston University, the lead author of the study. Dr. Amar discovered the LITAF transcription factor in 1999.

The researchers, who have applied to patent the mouse, are now researching whether other molecules work in synergy with LITAF. The study was published in the September 5, 2006, issue of the Proceedings of the [U.S.] National Academy of Science (PNAS).



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Boston University School of Dental Medicine