Antisense molecules are showing promise in attacking inflammation in preclinical experiments, according to findings published 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 inflammation mediator ICAM-1, worked in tissue culture to prevent expression of ICAM-1 on the surface of cells.

ICAM-1, an adhesion molecule on the surface of cells, helps white blood cells migrate out of the bloodstream to find their targets. Interfering with ICAM-1 is a popular new idea for fighting such diseases as allergic contact dermatitis, rheumatoid arthritis and psoriasis, as well as for preventing transplant rejections.

The scientists at Isis showed that antisense molecules could work at regions of the messenger RNA coding for ICAM-1 that were not necessarily expected to be crucial. "Non-obvious targets are important for patenting strategy," said Stanley Crooke, president and chief executive officer.

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

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

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

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

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