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Anacor Final Script 12/16/15

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Atopic dermatitis, also known as eczema, is one of the most common inflammatory diseases of the skin. It occurs in both children and adults. In fact, 4 out of 5 patients first experience symptoms by 5 years of age.

Atopic dermatitis is a chronic condition with red, inflamed, intensely itchy patches of skin that can become traumatized due to frequent scratching. This often results in thickened leather-like skin patches, also known as lichenification, raw and irritated lesions that may weep fluid, and may lead to serious skin infections.

Atopic dermatitis significantly reduces quality of life for both patients and parents due to disease symptoms as well as the stigma associated with a highly visible skin condition.

In atopic dermatitis, the balance between skin barrier and immune system function is disrupted. This leads to both skin barrier and skin immune system dysfunction.

Skin inflammation results when inflammation-causing molecules called cytokines are excessively released into the skin tissues.

Studies have shown that patients with atopic dermatitis have high levels of the enzyme phosphodiesterase 4, or PDE4.  The high PDE4 levels reduce the levels of cyclic AMP, resulting in increased levels of cytokines and promotion of inflammation in the skin.

The activity of cyclic AMP itself is regulated by PDE4, which degrades cyclic AMP rendering it inactive. High levels of PDE4, are associated with low levels of cyclic AMP.

Cyclic AMP communicates through an enzyme known as PKA to inhibit pro-inflammatory signaling pathways known as NFAT and NF-kappa-B which regulate inflammatory cytokines. Therefore cyclic AMP acts as a regulatory hub that suppresses the synthesis and release of multiple inflammatory cytokines that are important in atopic dermatitis.

By inhibiting PDE4, cyclic AMP levels can be elevated which inhibits cytokine production and reduces inflammation.

Excessive production of multiple cytokines due to low cyclic AMP levels—caused by abnormally high levels of PDE4 are believed to be an important cause of the skin inflammation seen in atopic dermatitis patients. In summary, normalizing levels of PDE4 may reduce inflammation and restore balance in the immune system in patients with atopic dermatitis.