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Patients with hereditary angioedema (HAE) never know when their next attack of swelling will come. Often starting in their teens or 20s, the swelling typically strikes the limbs and extremities, but patients may also have painful gastrointestinal swelling, disfiguring facial
swelling or life-threatening laryngeal
swelling. Children's Hospital Boston has been part of two clinical trials that may finally provide an emergency treatment
for this rare genetic disease, which
causes over-activation of the
complement system.
In the August Journal of Allergy and Clinical Immunology, Lynda Schneider, MD, of Children's Division of Immunology, and colleagues at 25 other institutions, reported that a single dose of ecallantide
(also known as DX-88) significantly relieved HAE attacks within four hours in 73
percent of patients (as compared with 25 percent in a placebo group). The drug was well tolerated at all doses tested, though some patients developed allergy
symptoms. Schneider is enrolling children in a multicenter trial that's testing C1
inhibitor, a second promising HAE drug.
These trials cap decades of research into a difficult and commonly misdiagnosed disease. "The pathways involved in HAE have only recently been understood," says Dr. Schneider, who has seen about 30 cases during the past 10 years.
Much of this understanding comes from the work of the late Fred Rosen, MD, former chief of Immunology at Children's. It's now known that HAE is caused by a genetic defect that depletes or damages C1 inhibitor, an important
regulatory suppressor of the contact, complement and coagulation cascades. The resulting biochemical cascade leads to excess production of bradykinin, increasing the
permeability of blood vessels; the resulting fluid
leakage causes the tissue edema. The two new drugs stop this process in somewhat different ways: Ecallantide blocks generation of kallikrein, the enzyme that directly causes bradykinin release, while C1 inhibitor replaces the protein that's lacking
or non-functional.
Pamela Johnson, now 31, would love to see either drug on the market, since she has only been able to access them through clinical trials. "I continued to have frequent, severe attacks, and I ultimately had to go on chronic androgen therapy to better control my disease," she says. "But as a woman, steroid treatment
carries significant side effects, which
is why research into new drugs is
so important."
For information about enrolling a child in
an HAE trial at Children's Hospital Boston,
contact 617-355-6127.
For more research news,
visit www.childrenshospital.org/research.
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