Clinical

Vascular disease underlies the most common causes of death in the developed world. In the late 1980’s the understanding began to emerge that inflammation was involved in progression of arterial disease. Since then considerable clinical and experimental evidence has pointed to a role for white blood cells in the progression of atherosclerosis, heart attack and stroke. In the past decade, technology to treat vascular disease has largely centered around angioplasty and the use of stents, to open affected arteries and maintain patency, respectively.

Unfortunately, while achieving overall great success clinically, these methods can sometimes result only in temporary benefit to patients: Treated arteries can re-occlude (i.e. restenosis). Since options for treatment after restenosis are limited, restenosis is a particularly important problem.

Multiple human and animal studies have demonstrated an association between IL-1α and the progression of atherosclerotic plaques. IL-1α expression in white blood cells has been found to be elevated in patients with both stable and unstable angina compared with healthy individuals. Cells associated with the atherosclerotic plaques, such as foam cells (FC), vascular smooth muscle cells (VSMC) and endothelial cells (EC) show elevated expression of IL-1α; and examination of atherosclerotic plaques from affected arteries of human subjects has demonstrated IL-1α expression on infiltrating white blood cells.

In animals, reduced ability to naturally downregulate IL-1 activity results in massive arterial inflammation with attendant infiltration of white blood cells (and consequent plaque) in the artery walls. These animals develop extensive vascular disease, characterized by arterial blockage, aneurysms and heart disease. Death is at an early age.

Using an anti-IL-1α True Human™ antibody to inhibit white blood cell infiltration of the artery may be broadly beneficial to vascular health. In particular, using such an antibody therapy after an angioplasty procedure may reduce subsequent arterial inflammation and provide a means to reduce the incidence or severity of restenosis.

The IL-1 system is a key player in regulating vessel health and disease. Inhibition of IL-1α is therefore expected to have important therapeutic impact on preserving vessel health during and after revascularization procedures.