Ruboxistaurin: PKC-β inhibition for complications of diabetes

Diabetes mellitus is the most common cause of blindness among working-age adults, with a prevalence of 7 - 8% of adults in the USA, and is one of the most common causes of renal failure requiring kidney transplant and the most common cause of non-traumatic lower limb amputation in developed nations [1]. The role of the intracellular signaling enzyme protein kinase C (PKC) in the development of diabetic complications has become a field of intense research interest. An inhibitor of the PKC-beta isoform ruboxistaurin (RBX) has in vitro and in vivo benefits in ameliorating disturbances of cell regulation and blood flow related to hyperglycemia. The benefit of RBX for peripheral neuropathy has not been successfully demonstrated in Phase III trials. Although there was a beneficial effect of RBX on nephropathy in a pilot study, there has been no further clinical development for this indication. The major cause of visual disability - diabetic macular edema - seems to respond to RBX treatment with both anatomic and functional benefits. The manufacturer, Eli Lilly Co., has received an approvable letter from the FDA for the prevention of vision loss in patients with diabetic retinopathy with RBX, pending results of additional clinical trials for this indication.