INFLAMMATION

Inflammation is a reaction of the body to actual or perceived injury and is characterized by pain, heat, redness and swelling in the affected area. Under normal circumstances inflammation is a protective response, the goal of which is to eliminate both the initial cause of injury, such as bacteria or toxins, and the consequences of such injury, such as dead cells and tissues. However, if triggered or directed inappropriately, the inflammatory response can itself become harmful, leading to cell, tissue and organ destruction. Examples of such inappropriate or pathologic inflammation include some of the most common and disabling diseases, such as rheumatoid arthritis, Crohn's disease, lupus, psoriasis, asthma and chronic bronchitis. Although several different diseases and mechanisms can trigger the inflammatory response, the underlying process in each of these diseases is closely related, involving a number of different inflammatory cell types and chemical signaling factors.



Ion channels may play a role in both the activation and modulation of the inflammatory response. For example, the activation of T-lymphocytes, an important cell type in this response, is believed to involve the influx of calcium into these cells through specialized ion channels. We believe the opening and closing of ion channels may modulate the movement of some immune system cells to the site of inflammation, the release of chemical signaling factors from immune system cells, and the proliferation of these cells in response to activation of the immune system.



We have recently completed profiling the distribution of human ion channels in various cells of the immune system. As a result, we have identified ion channel targets that are expressed at high levels in some immune system cells and that may play an important role in modulating the inflammatory response. We have discovered compounds that are active in vitro against some of these targets, leading to decreases in calcium entry into immune system cells, decreases in immune system cell proliferation, decreases in immune system cell migration into tissues and other measures of inflammatory responses. We have also demonstrated effects of some of our compounds in animal models of inflammatory diseases.

Within our inflammation program we are currently studying the potential utility of

senicapoc, our novel IK channel inhibitor, in preclinical models of several immune and

inflammatory diseases.  Senicapoc has been tested in several clinical trials as a result

of our studies of this compound in sickle cell disease, and thus far has demonstrated a

favorable safety profile.  Furthermore, the target of senicapoc, the IK channel, has been

shown in a number of preclinical studies conducted both at Icagen and at other

laboratories to be an important potential target for the treatment of these conditions.

Icagen may selectively consider potential corporate partnership opportunities in its inflammation program.