The work is from Avant. Relevant to the properdin work (and ongoing chemistry efforts at Janssen??). Interesting concept.... sialyl Lewis A and analogs have largely failed (CYTL, AMGN.... TXB has one in development, and PDLI has anti-selectin MAbs). GLIA and Janssen were into an interesting field much earlier than most.....
Neuronal Protection in Stroke by an
sLex-Glycosylated Complement Inhibitory
Protein
Judy Huang, 1 Louis J. Kim, 1 Richard Mealey, 2 Henry C. Marsh Jr., 2
Yuan Zhang, 1 Andrea J. Tenner, 3 E. Sander Connolly Jr., 1
David J. Pinsky 1*
Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed
C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to
simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble
complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLex) to inhibit complement activation and
endothelial-platelet-leukocyte interactions. sCR1 and sCR1sLex colocalized to ischemic cerebral microvessels and
C1q-expressing neurons, inhibited neutrophil and platelet accumulation, and reduced cerebral infarct volumes. Additional
benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.
1 Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
2 Avant Immunotherapeutics, Inc., 119 Fourth Avenue, Needham, MA 02494, USA.
3 University of California, Department of Molecular Biology and Biochemistry, Irvine, CA 92697, USA. |
