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Novel therapy improves immune function in teen with rare disease
Date:4/14/2011

y functioning immune cells or inserting DNA to correct the defective gene, Orange and colleagues identified and made use of an alternative pathway to restoring immune function.

The researchers used interleukin-2 (IL-2), a cytokine, or cell-signaling protein, a naturally occurring molecule with a key role in the immune system. In a series of cell studies, they revealed mechanisms by which IL-2 signals control actin filaments, cell structures that enable natural killer cells to mount an effective immune response.

"IL-2 enables NK cells to become cytotoxicto kill foreign cells," said Orange. "This happens even in the absence of WASp, the protein that is deficient in WAS patients." Researchers in Orange's laboratory found that in cell cultures, IL-2 induced the function of a protein called WAVE2, similar to WASp, but independent of it. The WAVE2 protein acted similarly to WASp, but was accessed through an alternative pathway that enables function in NK cells.

Most importantly, IL-2 achieved clinical laboratory benefits in a teenaged patient in this study. The patient, a 13-year-old boy with mild WAS, had suffered recurrent respiratory tract infections and several of his uncles had died prematurely from blood-cell cancers.

The researchers injected the patient with pharmaceutically produced IL-2 in three treatment courses over 27 weeks. At the end of treatment, the patient's NK cells had cytotoxicity nearly identical to that of a healthy control subject. He tolerated the IL-2 treatment well, with only minor skin reactions at the injection site.

"Although follow-up studies will be necessary to investigate long-range benefits and test IL-2 in additional patients, the initial results are encouraging," said Orange. "If cytokines can provide clinical benefits with low toxicity, this may represent an important advance and opportunity for all patients with Wiskott-Aldrich syndrome."


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Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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