NEW YORK -- A brain inflammation in macaque monkeys thatresembles multiple sclerosis in humans cleared up completelyafter a seven-day treatment with a monoclonal antibody (MAb)that targets a pro-inflammatory "cell-trafficking" molecule.

George B. Rathmann, chairman, president and chief executiveofficer of Icos Corp. in Seattle, described the unpublishedpreclinical trial here Thursday at the Third Annual HealthcareConference of Oppenheimer & Co. Inc.

Icos' strategy, Rathmann said, is "to target the earliest stages inthe inflammatory process, and is focusing on asthma andrheumatoid arthritis, along with multiple sclerosis (MS)."

His chosen primate model contracts experimental allergicencephalomyelitis (EAE) when white blood cells migrate intothe brain, Rathmann explained. Icos' scientists have learned tointercept this cell trafficking, he added. Leukocytes theyseeded into the monkeys' brains migrated and multiplied to setup foci of inflammation, and showed symptoms of neurologicdysfunction similar to acute MS episodes.

The scientists then inserted pencil lead-thin tubes into theinflamed areas -- outlined by magnetic resonance imaging --and infused Icos' patent-pending, humanized MAb specific forleukointegrin. This is one of the four small adhesive moleculesthey have discovered that drive the attachment, movementand passage of trafficking cells through and beyond bloodcapillaries. After seven days of this treatment, Rathmann said,"what we see is a total resolution of EAE disease in themacaque."

In dozens of such animal trials, Rathmann told BioWorld,symptoms did not recur as far out as 45 days. But Rathmanncautions that MS is an episodic disease that waxes and wanesunpredictably.

"To think we've completely wiped out the residual thing thatinitiates symptoms periodically seems unlikely," he said. Still,Icos' ability to reverse cell trafficking in its animal model"could be an important discovery with respect to MS," he said.

MS, Rathmann told his audience at the conference, affects250,000 Americans, who spend $100 million annually onmedical bills. The cost to society is $2 billion a year, he said.

Before phalanxes of leukocytes move into the fast lane of celltraffic to trigger inflammation, they must be activated. A keyenzyme in this signal induction of activation isphosphodiesterase (PDE). Icos has a "broad program" of PDEmodulation jointly with Glaxo on a 50-50 profit-sharing basis,Rathmann said. Icos has already identified 10 isozymes --molecular variants -- of PDE and is looking at PDE inhibitors totreat asthma.

Many biotech companies are now pursuing signal transduction,Rathmann told BioWorld. "It's become a magic wand -- a littlebit like interferon a decade ago. You rub it on a stock brokerand it produces $40 million."

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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