Researchers from the Department of Life Sciences and the National Institute for Biotechnology in the Negev at BGU in collaboration with Teva Pharmaceutical Industries LTD. have engineered a natural immune system receptor into a promising drug candidate for the treatment of Psoriasis.
Psoriasis is an autoimmune disease that affects millions of people, causes great suffering, and costs billions to health care systems worldwide. The main reason for the outbreak of Psoriasis is the disturbance of the natural balance between pro-inflammatory signals and signals that inhibit inflammation. In Psoriasis the outcome of this imbalance is inflammation and unregulated division of the skin cells.
One of the key signals involved in the progression of Psoriasis is the immune system protein Interleukin 17 (IL-17). In a paper just published in the journal Chemistry and Biology entitled: “Directed Evolution of a Soluble Human IL-17A Receptor for the Inhibition of Psoriasis Plaque Formation in a Mouse Model”, Dr. Marianna Zaretsky and Prof. Amir Aharoni from BGU together with Dr. Liora Sklair-Tavron, Dr. Joel Kaye and Revital Etzyoni from Teva developed a method to inhibit IL-17 pro-inflammatory signals. The team engineered the extra-cellular soluble domain of IL-17 receptor to bind with high affinity to the natural IL-17 protein. The engineered IL-17R was developed by a directed evolution approach, in which an ensemble of mutants is screened for improved properties.
The resulting engineered IL-17R had a much better binding affinity and possessed more stability relative to the natural IL-17R receptor, making it a promising drug candidate. In the paper, the team showed that this engineered IL-17R is highly effective in reducing IL-17 induced inflammatory signals in mice models. Moreover, injection of the engineered IL-17 receptor into a mouse model with acute human Psoriasis led to the abolishment of the symptoms, essentially curing the disease.
“Using directed evolution to improve the properties of the IL-17 receptor we have created engineered mutants that might prove there is a viable treatment for patients with severe Psoriasis that do not respond to current drugs.
“Since the directed evolution method can be applied to other receptors involved in autoimmune diseases and cancer, I believe that we are just starting to unravel the potential of this approach” Aharoni added.
Aharoni was the recipient of a prestigious ERC Starting Grant in 2011.