European doctors report saving the life of another septic shockvictim with nitric oxide inhibitors, unpatentable non-biotech drugsthat come off the shelf of chemical supply houses.
The latest report on Saturday in The Lancet was accompanied bycorrespondence from other physicians advising against use of theinhibitors without further animal studies.
The drugs in question are analogs of the amino acid l-arginine, andthey block the arginine-dependent production of nitric oxide (NO),which dilates blood vessels. In septic shock, bacterial endotoxininduces an outpouring of NO that may be causing blood pressure tofall. Deprived of sufficent blood flow, organs fail and death is highlylikely.
In December, British doctors reported in the journal on a patientwith septic shock that had resisted all therapeutic attempts, butwas rescued by a NO inhibitor.
This week, doctors in Zurich report saving a septic shock patientwith the NO blocker NMMA. The patient had been in intensive carefor more than four months, and a fatal outcome seemed likely. "Inthis desperate setting ... we decided to administer this agent, andthe father of the unconscious patient agreed," the doctors wrote. The29-year-old patient recovered from profound hypotension within 24hours following NMMA.
However, Missouri physicians writing to the journal this week alsowarn that NO may have important roles to play in preventing com-plications from sepsis, and caution that more work in animals isneeded before the drugs that block NO are tested further in humans.
NO inhibitors are unlicensed and are obtained through chemicalsupply houses. British researchers at Wellcome ResearchLaboratories in Kent have been testing the arginine analogs in rats.They have noted that the two analogs, L-NMMA and L-NAME, cannotbe patented.
NO blockers potentially could supplant recombinant monoclonalantibodies and cytokines in septic shock. Centocor Inc.(NASDAQ:CNTO), Genentech Inc. (NYSE:GNE), Syner-gen Inc.(NASDAQ:SYGN), and Xoma Corp. (NASDAQ:XOMA) are all purusingbiotech solutions to the infection.
"Unlike agents to neutralize endotoxin and individual cytokines,various combinations of which may be needed for different types ofshock, NO synthase inhibitors offer a single therapeutic approach,"the Wellcome group concluded in December.
-- Roberta Friedman, Ph.D Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.