The potential clinical benefit of these new findings is that gamma secretase inhibitors may so on be available for testing in the clinics. One potential side effect of these drugs is that they inhibit other pathways besides Notch. In addition, inhibiting Notch may cause side effects because this protein is used in a wide variety of cellular processes. The new mouse model described in this paper may be particularly useful for identifying the consequences of turning Notch off in different organs, an important issue for assessing potential side effects of pharmacologic Notch inhibitors.

The current work provides the rationale for determining whether manipulating Notch signaling will be useful in combating such diseases as parasitic infections, asthma, and inflammatory bowel disease. "The exciting possibility is that therapies are available," says Pear. "The challenge, however, is determining their efficacy and safety."

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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
17-Oct-2005