The Wall Street Journal-20080122-Genentech Finds Lupus-Linked Genes
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Genentech Finds Lupus-Linked Genes
Genentech Inc.'s discovery of two new genes linked to lupus raised hopes of earlier diagnosis and better targeted treatment of the autoimmune disease, which affects an estimated 1.5 million Americans.
Genentech already has two experimental drugs in Phase III, or late stage, studies to treat lupus: a compound called an anti-CD20 antibody, and its older drug Rituxan, widely used as a cancer treatment. The latest advance restores the company's momentum in combating lupus after two patients who had taken Rituxan -- not yet an approved treatment for the illness -- died of brain infections in December 2006. The two patients weren't study subjects and had other risk factors, Genentech has said.
Chief Executive Art Levinson this month highlighted his hopes that the lupus trials will help boost the flow of important data emerging from Genentech's pipeline of new drugs in development this year after "a quiet period."
Analysts fear the South San Francisco, Calif., biotech giant's earnings growth could flatten unless it can score another big hit to supplement revenue from its blockbuster Avastin.
A number of other companies also are developing lupus treatments, including Amgen Inc., a biotech rival based in Thousand Oaks, Calif.
Discovery of the new genes, labeled BLK and ITGAM, was reported by Genentech scientist Timothy W. Behrens and his colleagues in the New England Journal of Medicine's online edition on Sunday. The report coincided with that of a rival team from the International Consortium for Systemic Lupus Erythematosus Genetics in the journal Nature Genetics.
Dr. Behrens's team believes the BLK gene influences one component of the immune system -- B cells -- while the ITGAM gene affects another, T-cells, in ways that trigger the immune system to attack a lupus patient's own body like friendly fire.
Scientists hope the findings will improve the diagnosis and targeted treatment by predicting patient response to drugs. Lupus attacks many organ systems and can cause death, often from cardiovascular damage. Women and minorities suffer the brunt of lupus cases.
"Way too many young women have strokes and heart attacks," Dr. Behrens said. "This disease attacks blood vessels and every organ has a blood supply, so it manifests itself in the kidney, brains, joints, heart."
Dr. Behrens added that lupus is often difficult to diagnose and that "it's not unusual for someone to go several years with vague and undiagnosed symptoms."
Genentech's findings are relevant to continuing studies because Rituxan targets B cells, the very cells that express the newly discovered BLK gene. But BLK and ITGAM are just two of about 10 genes linked to the immune disorder, which may eventually be discovered to be linked to another 20 or 30 genes, Dr. Behrens said. The findings may help predict who can benefit from treatment, though Dr. Behrens cautioned the timeline for such applications is uncertain.
The Behrens paper not only adds to the growing number of genes linked to lupus, but is significant in that it uses a powerful genetic-testing technology that is yielding insights into many previously unrecognized genes linked to disease, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, a unit of the National Institutes of Health.
The findings aren't expected to produce a full picture of the disorder just yet, because none of the study subjects was African- American, a group that suffers disproportionately from lupus.
