Antisense molecules are showing promise in attackinginflammation in preclinical experiments, according to findingspublished by scientists at Isis Pharmaceuticals Inc.

In the Sept. 25 issue of the Journal of Biological Chemistry,the company showed that oligonucleotide molecules,constructed to block the genetic message for the inflammationmediator ICAM-1, worked in tissue culture to preventexpression of ICAM-1 on the surface of cells.

ICAM-1, an adhesion molecule on the surface of cells, helpswhite blood cells migrate out of the bloodstream to find theirtargets. Interfering with ICAM-1 is a popular new idea forfighting such diseases as allergic contact dermatitis,rheumatoid arthritis and psoriasis, as well as for preventingtransplant rejections.

The scientists at Isis showed that antisense molecules couldwork at regions of the messenger RNA coding for ICAM-1 thatwere not necessarily expected to be crucial. "Non-obvioustargets are important for patenting strategy," said StanleyCrooke, president and chief executive officer.

Patents are filed on every antisense molecule described in thepublication, Crooke told BioWorld, "and we expect the patentsto issue."

Isis is looking for ways to get the antisense strategy intoclinical trials quickly, and is also investigating the celladhesion molecule ELAM "and other inflammatory targets,"Crooke said.

Isis (NASDAQ:ISIP) of Carlsbad, Calif., on Monday said it hasreceived a PhaseISIS I small business innovation research grantfor studying the fate of antisense drugs within the body.

-- Roberta Friedman, Ph.D. Special to BioWorld

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