The 48-year-old Texas man was referred to Coffey from the University of Texas-Southwestern Medical Center in Dallas with endless vomiting - before treatment, he was vomiting an average of 70 times a week. "He was miserable," Coffey said.

However, because of a severe underlying lung disease, he could not undergo surgery. The Food and Drug Administration and the institutional review boards of both academic centers gave "compassionate use" approval for a one-month course of a new drug, a monoclonal antibody that blocks activation of the EGF receptor called C225.

GFa is a cousin to the epidermal growth factor whose discovery won Vanderbilt's Stanley Cohen, Ph.D., a Nobel Prize in Medicine. EGF and TGFa are among six ligands that can activate the EGF receptor, which Cohen also identified with Graham Carpenter, Ph.D., Ingram Professor of Cancer Research and Biochemistry. The EGF receptor is involved in the overgrowth of cells that is characteristic of cancer.

Coffey's laboratory had previously shown that TGFa is produced in the normal stomach, where it stimulates growth of gastric epithelial cells, suppresses acid production and protects against injury to the stomach lining, most likely by increasing mucous levels - all features found in patients with Mntrier's disease.

To investigate their suspicion that enhanced EGF receptor signalling was a cause, Coffey's team also studied tissue samples from 20 patients with the disease and found excessive amounts of TGFa. Further evidence: mice engineered to overproduce TGFa in the stomach exhibited virtually all the features of Mntrier's disease.

The effect of C225 in this patient was quick and impressive, the scientists report. "By
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Contact: Cynthia Manley
cynthia.manley@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
6-Dec-2000