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A natural immune-system hormone implicated in vascular failure occurring in septic shock and cerebral malaria can be neutralized by two urine proteins recently discovered at the Institute. Furthermore, since the hormone may contribute to tissue damage accompanying autoimmune disorders, graft rejection and graft-versus-host disease, the proteins may be effective against these disabilities as well.
The hormone in question, known as "tumor necrosis factor" (TNF), is formed by white blood cells in response to injury or infection. However, TNF production can become excessive, leading to the destruction not only of substances foreign to the body but also of healthy tissues, thus inducing the onset of various diseases. Prof. David Wallach of the Institute's Department of Membrane Research and Biophysics, along with Ph.D. student Harmut Engelmann (M.D.) and Dr. Dan Aderka of Ichilov Hospital, discovered two urinary proteins called TBPI and TBPII (TNF-binding proteins I and Ii) that inhibit TNF activity.
The purification and amino acid sequencing of the TBPs was carried out by the group of Prof. Wallach in collaboration with Institute researchers Prof. Menachem Rubinstein, Dr. Dalia Rotman and Dr. Daniella Novick. Based on the sequencing, Prof. Wallach and doctoral students Yaron Nophar, Oliver Kemper and Cord Brakebosch cloned the genes for these proteins. Analysis of the gene structure revealed a close evolutionary relationship between the TBPs and segments of known hormone receptors.
Patents for the TBPs and their genes have been registered by Yeda Research & Development Co. Ltd., and recombinant TBP is already being synthesized by an Israeli company, InterPharm. Preclinical trials have shown that natural and recombinant forms of the protein, in microgram amounts, effectively protect against septic shock in mice. Clinical trials in humans are expected soon.
Prof. Rubinstein holds the Edna and Maurice Weiss Chair of Interferon Research.
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