Mycoplasma Arthritidis Mitogen (MAM) Superantigen: a Unique Immunomodulator

MAM is a superantigen (SAg) produced by M. arthritidis, a bacterial species that causes murine arthritis, toxic shock and dermal necrosis. MAM has very little sequence homology with any other SAg, but it is a potent immunomodulator of murine and human T-cells, B-cells, NK cells and macrophages. In this invention, the MAM molecule was expressed in E. coli, and the inventors found that MAM is not notably toxic when injected into mice, but a single minute does profoundly influences the immune system of the animals. Depending on a number of different genetic factors that predispose to susceptibility (or resistance) to autoimmune and inflammatory diseases, rapid changes in type 1 and type 2 cytokine profiles were observed. Also, it was found that the diverse interactions of MAM with TLR2 and TLR4 differentially upregulated B7-1 expression and cytokine production, and ultimately differentially affected arthritis and toxic shock induced by M. arthritidis.

Benefits
Upon direct binding to MHC class II molecules, SAg is capable of polycolonally activating a large pool of T lymphocytes sharing a compatible and common V-beta region of the TCR. MAM, a zinc-dependent SAg, has a unique property of inducing a spontaneous, chronic form of arthritis in genetically susceptible strains of rodents that histologically resembles rheumatoid arthritis in humans. Potential market applications of MAM are:
*Providing a new arthritic mouse model for a better understanding of the mechanisms involved in human rheumatoid arthritis pathogenesis.
*Therapeutic use in blocking toxic shock because MAM interacts with the LPS-signaling pathway in a unique manner.
*Providing new targets for autoimmune disease therapeutic intervention
*Used as a therapeutic agent to increase host defense, particularly in those diseases associated with immunodeficiency, i.e., AIDS and cancer, because MAM enhances immune responses with no apparent toxicity.
*Used to bolster host defenses against infectious agents.

Stage of Development
Three patents have been issued from the U.S. Patent and Trademark Office, #5,639,869, #5,795,974, and #5,872,233.
This technology is available for licensing under either exclusive or non-exclusive terms.

Additional Info
*Cole BC, Mu HH, Sawitzke AD. (2000). The mycoplasma superantigen MAM: role in arthritis and immune-mediated disease. Int J Med Microbiol. 290(4-5):489-90.
*Mu HH, Humphreys J, Chan FV, Cole BC. (2006) TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis. Cell Microbiol. 8(3):414-26.

Inventor(s): Curtis Atkin, Barry Cole, Arnold Oliphant, Ann Pole

Type of Offer: Licensing



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