'We thought we could study its biology and perhaps develop therapeutics , ' says Ray Goodwin , a pioneering TNF researcher at Immunex. 'We hadn't specifically decided what disease to work on at that point
.But there were plenty of diseases to choose from.''.Why? Many ailments involve inflammation , Goodwin
says , and TNF promotes inflammation.In small doses , TNF also helps damaged cells to repair themselves.This makes TNF a critical player in wound healing and tissue repair.But TNF production sometimes continues after its job is done , and it destroys healthy tissue.In rheumatoid arthritis , excess TNF thins the cartilage that cushions bones.In congestive heart failure , excess TNF gradually kills off the muscle cells that power the heart's contractions.As in JRA , TNF also attacks the connective-tissue 'struts'' that hold muscle cells together , thinning the heart's wall , enlarging the heart and forcing it to work harder.
says that TNF triggers inflammation by locking into special receptors on the cell surface , which cues a kind of bucket brigade of signaling molecules to convey a message from the cell's surface to the genes in its nucleus.Receptors' role in this process makes them a valuable target for drug discovery , he
says.If you know the TNF receptor's makeup , you can create a decoy receptor that will lock_up any extra TNF that's around , preventing it from triggering the signaling cascade.This is the same tactic that cells use in nature to keep inflammation in check ; they release TNF receptors from their surface to mop_up excess TNF. 'A lot of companies were going after the TNF receptor , ' Goodwin says.Goodwin
colleagues worked_out a way to prompt TNF-receptor genes to make the receptor on demand.Immunex scientists initially tried using the receptor to block overwhelming infections of the bloodstream.It didn't work.But clinical trials in more than 1 , 000 patients indicated that the decoy TNF receptors in Enbrel dramatically reduced pain and inflammation in adults with rheumatoid arthritis ( RA ) .In 1998 , Immunex
won government permission to market Enbrel to treat RA in adults.Enbrel isn't cheap ; it costs about $ 13 , 000 a year.