Principal Investigators:
Richard Margolis, M.D., Ph.D., Department of Pharmacology, New York University School of Medicine
Renée Margolis, Ph.D., Department of Pharmacology, SUNY Health Science Center, Brooklyn

Lymphocytes, neutrophils and monocytes respond to invaders in extravascular tissue by travelling along the endothelial wall of blood vessels until they reach the problem area and enter the surrounding tissue and lymphatic system to mount an attack on the antigens. This process is directed by molecules called "selectins" or LEC-CAMS (leukocyte endothelial cell-cell adhesion molecules) which appear on the surface of platelets or endothelial cells in response to inflammatory or thrombogenic agents. Selectins guide the leukocytes to specific signal ligands that halt cell movement and trigger cell adherence and penetration of the endothelial wall. Sometime this important protective mechanism may go awry and give misdirected neutrophil attack causing acute inflammation trauma, reperfusion injury and acerbated myocardial infarction.

Recently, it was shown that the sialyl Lewis X (SLex) carbohydrate structure, which is found on the endothelial wall, is one of the ligands recognized by selectin molecules. SLex is also a known tumor antigen and may play a role in recruiting platelets (which are known to have tumor assisting activity) to tumor cells. Clearly, any agent that can disrupt the selectin - SLex recognition process has enormous therapeutic potential for the treatment and control of leukocyte mediated disease and tumor formation. Therefore, an important goal of carbohydrate-based drug development is the identification of molecules which can recognize SLex and/or block its recognition by selectins.

Description of the Project
Dr. Richard Margolis and Dr. Renée Margolis have identified neurocan, a chondroitin sulfate proteoglycan which is thought to play a role in defining a destination for migrating axons that form the cortical plate, and in delineating pathways for early axonal extension in mammalian brain. The investigators have obtained the complete polypeptide coding sequence and shown that its C-terminal contains epidermal growth-factor-like domains, a lectin-like domain, and a complement regulatory protein-like sequence. On the other hand, LEC-CAMS have a lectin-like domain followed by an EGF-like domain and complement regulatory protein-like sequences. The similarity between the domains of neurocan and LEC-CAMs suggests that neurocan may also have SLex binding activity. The investigators have shown interactions with cell adhesion molecules which may be carbohydrate mediated.

Applications:
NYU is seeking an industrial partner to assist in further developing and commercializing neurocan technology. Potential uses include treating pathology related to leukocyte-endothelial cell recognition, allergic and inflammatory conditions, tissue trauma, and tumor formation.

Patent Status
NYU has an issued U.S. Patent covering this novel technology.

For further information please contact:
Jane V. Scott, Ph.D.
jane.scott@med.nyu.edu
New York University
Office of Industrial Liaison
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189