Genentech Connection:
Allergies
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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