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Genentech Connection:


With the advent of recombinant DNA technology, immunologists have been able to clone and purify the receptors for IgE on the mast cell and a whole family of both B and T cell receptors and growth factors (cytokines) which regulate IgE production in the body. Biochemists have also made great strides identifying the proteins and signaling pathways within the mast cell which participate in the allergic cascade. The development of genetically engineered mice in which the genes for these proteins have been knocked out and the proteins themselves removed from the animal has dramatically changed the way scientists view the relative importance of many of the growth factors and receptors in determining what causes IgE production.

Currently researchers are pursuing new therapies to treat IgE mediated allergies using several approaches. One approach would be to block B cell IgE production by developing inhibitors to growth factors or growth factor receptors. The problem with this approach is that the drug you develop could adversely inhibit other vital functions of the immune system in addition to IgE production. Another approach is to develop small molecule inhibitors of the proteins inside the mast cell that control histamine release. These inhibitors would have to be specific to mast cells only. This is a problem since many of the proteins involved in intracellular signaling are shared by different cell types so you again could have the problem of unwanted side effects.

Genentech researchers are working on a novel and potentially more effective therapy for allergic diseases. IgE is the trigger for unleashing the mast cell arsenal. If it is possible to make a drug which prevents IgE from getting to its "post" on the mast cell it cannot signal the mast cell that a pollen grain or peanut has entered the body. The "mast cell cannot see these foreign substances without IgE so it will not fire. If histamine is not released by the mast cell the person will not wheeze and sneeze when they inhale the pollen or dust mite dung.

Genentech researchers have designed a drug that does exactly this. This drug is called E25 and it is currently being tested in people with hay fever and asthma to determine if it will prevent the mast cell from releasing it's arsenal of debilitating chemicals. If the drug works millions of allergy suffers till no longer be victimized by pollen grains, mold, dust mite dung and the family cat!

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