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Potential Use of CCL2 for the Treatment of Inflammation
Yeda R&D Co. Ltd Israel flag Israel
Abstract ID: 1424
The human immune system is highly streamlined and usually highly efficient. Commando squads of purpose-built cells, called lymphocytes, respond to chemical messages sent by distressed areas of the...
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Introduction/Background

The human immune system is highly streamlined and usually highly efficient. Commando squads of purpose-built cells, called lymphocytes, respond to chemical messages sent by distressed areas of the body, homing in on the offending antigens. This kind of inflammatory response is desirable when the body is legitimately under threat. The system can go awry, however, in several ways. The body can mistakenly send a distress call to the cells responsible for an immunological response, or those cells, heeding the call toward a real danger, can dramatically overreact.

In the first case, the diligent commandos respond according to instructions - but in the absence of an invader, they attack the host. This constitutes an autoimmune response, like in rheumatoid arthritis, which can cause problems ranging from mild, stubborn inflammations to life-threatening conditions. In the second incorrect immune response, the lymphocytes' attack on the antigen is so far out of proportion as to threaten the health of the host. This kind of exaggerated reaction can lead to an inflammatory disease like asthma that results in disorder of the bronchial airways that is characterized by intermittent episodes of airway obstruction and wheezing.

Today both rheumatoid arthritis and asthma present a treatment challenge. Currently 2.5 million Americans (1% of US population) suffer from rheumatoid arthritis. No curative treatment is available and the existing medications aim to reduce inflammation, decrease pain, improve joint function, stop joint damage, and prevent disability, have substantial side effects. Approximately 20.5 million Americans currently have asthma and no definitive treatment is currently available. Whilst medications are used in order to control chronic symptoms and prevent asthma attacks, this is done with partial success and quite a lot of side effects.

The surveillance of the body for foreign antigens is a critical function of the immune system. Lymphocytes migrate from the blood into tissues and secondary lymphoid organs, and return to the blood via lymph vessels and the thoractic duct. The majority of lymphocytes are capable of tissue selective trafficking (homing), recognizing organ-specific adhesion molecules on specialized endothelial cells.

Cell migration is controlled by multi-step processes that include chemoattraction, cell-cell adhesion, and transmigration through cell layers. Chemotactic signals control leukocyte navigation by regulating migration from the blood into tissues, as well as subsequent localization within the tissue microenvironment.

Aims/Hypothesis

CCL2 (MCP-1 in humans or JE in mice) is a chemokine that was found to be involved in various inflammatory responses.

Research

The present invention (patent pending) describes the use of low levels of CCL2 to regulate migration of lymphocytes. This invention relates in general to methods and pharmaceutical compositions for treating inflammation, and more particularly, to a method for down-regulating adhesion and migration of lymphocytes by ultra-low dosages of CCL2.

Researchers from the Weizmann Institute of Science have shown that CCL2, possibly via its major adhesion attenuating properties has a dramatic inhibitory effect in the development of asthma, rheumatoid arthritis and IBD.

Thus, low levels of circulating CCL2 can exert global suppressory effects on T-cell trafficking and differentiation within inflamed lymph nodes and may be clinically beneficial as an anti-inflammatory agent in additional inflammatory diseases.

Conclusion

Our research has shown the potential treatment of inflammatory and autoimmune diseases like asthma, RA and IBD with CCL2.

Relevance/Opportunity

We are currently seeking licensing or codevelopment partnerships. Please enquire quoting reference no. 1424.
FEATURED
Last Updated May 2015
Technology Type THERAPEUTIC
Phase of Development PRECLINICAL
CORPORATION