Grant: Proof of Principle Program - Phase I

Psoriasis is a chronic skin disease that affects an estimated 1 to 3 % of the world's population. Psoriasis has been shown to affect health-related quality of life to an extent similar to the effects of other chronic diseases and has been linked to rheumatoid arthritis, diabetes, cardiovascular disease, hypertension and obesity. Unfortunately, all the current treatments for psoriasis have specific safety concerns. One of the difficulties in treating psoriasis is that there are numerous interactions amongst various cellular components of the immune system. More specifically, the combination of a specific pair of proteins (HLA-Cw6 and KIR2DS1) in a person's genetic make-up is a major risk factor for psoriasis. In fact, ~50% of psoriasis patients carry the HLA-Cw6 gene and these individuals usually have a younger age of onset and an increased disease severity. As a result, we have designed a peptide (HLA peptide; provisional patent No. 61/346,255) to provide an improved treatment for psoriasis by blocking the interaction between HLA-Cw6 and KIR2DS1. We have previously shown that the peptide binds to the KIR2DS1 receptor with comparable affinity to full length HLA-Cw*/KIR complexes. In the following proposal we are requesting funding to validate and optimize the HLA peptide using cell-based assays so that it will be feasible to out-license this technology to a receptor company. This peptide, which specifically targets the HLA-Cw6/KIR2DS1 interaction, is expected to exhibit superior safety and efficacy as compared to the current leading biological therapeutics. As an added benefit, the smaller HLA peptide would be less expensive to produce than the current biologics on the market and thus would be more readily taken up by the health care system and insurance companies.