Work in our lab and others has implicated an excess of normal epidermal growth factor receptor (EGFR) signaling between cells of the stomach in the development of Ménétrier's disease.
Cells normally send and receive growth signals so that the correct cellular structure and stomach physiology can be maintained. The EGFR is a protein receptor on the surface of cells that is known to be responsible for cell signaling in many different situations. Although normal EGFR signaling is important for survival, excess EGFR signaling can cause disease. Increased levels of EGFR signaling have been demonstrated in many different forms of cancer, and our data has implicated excess EGFR signaling in the development of Ménétrier's disease. The stomach normally contains a variety of cell types including surface mucous cells that secrete mucus to protect the stomach as well as other cell types which produce factors critical for normal digestion, including parietal or acid-producing cells. In Ménétrier's disease patients' stomachs, there is an excess of mucus-producing cells and a lack of the other important cell types, most notably parietal cells. We believe that the excess EGFR signaling in these patients' stomachs causes too many of the mucous cells to proliferate which impairs the development of the other important cell types. This causes the abnormal cellular structure of the stomach in Ménétrier's disease and ultimately leads to the symptoms reported by Ménétrier's disease patients.
We have hypothesized that if we block the excess EGFR signaling present in the stomachs of Ménétrier's disease patients, then we might be able to treat this disease.
C225 (cetuximab, a drug developed by Imclone Systems) is an experimental drug that does just that. C225 blocks EGFR signaling, and it has been used in a number of clinical trials with cancer patients. We initially treated a patient who had severe symptoms from Ménétrier's disease with this drug with great succes and our work was published in The New England Journal of Medicine.
For this reason, we have expanded our work into an FDA-approved clinical trial, and have now treated additional patients with this uncommon disease. A more advanced description of our research on Ménétrier's disease is presented in the "More Information" section of this site.
To begin studying C225's effects on Ménétrier's disease, we treated a single patient with C225 once a week for a period of one month. Twenty-four hours after this patient's first treatment, he reported marked improvement of his symptoms and the lining of his stomach showed reduced levels of cell proliferation. After the full month (comprised of four weekly treatments) was complete, the patient showed remarkable improvement with respect to both quality-of-life parameters and biochemical parameters. For example, prior to treatment the patient was vomiting 70 times a week, but following one month of treatment he was vomiting only one time per week. Moreover, the patient showed reduced protein loss (the cause of peripheral edema or swelling) and the cellular structure of the patient's stomach showed signs of returning to normal with the emergence of parietal (acid producing) cells which were absent prior to treatment.
There is considerable variablility in the presentation of Ménétrier's disease, and we have seen quantitative improvements in additional patients' symptoms. Improvements have been noted in symptoms ranging from the typical nausea and vomiting with peripheral edema (described above) to less-commonly seen manifestations of Ménétrier's disease (i.e. blood loss in the stomach).
Although there are limited numbers of patients with this disease, we are encouraged by our results thus far, and are seeking additional patients to treat.