Staff Scientist: Dr. Daniela Novick

In the summer of 2015, a three-month-old baby was admitted to a hospital in Philadelphia, Pennsylvania, with severe inflammation of her colon. The doctors saw that she was suffering from a congenital autoimmune disease that affected all of her systems, and they did not expect her to live. After conducting genetic testing on the baby, they found that she carried a recently identified, very rare genetic mutation. Yet, in November it was reported that the girl was home with her parents and in full remission. The drug she was given – and is still taking – is based on a discovery made by the Weizmann Institute’s Dr. Daniela Novick and Prof. Menachem Rubinstein, in work was done in collaboration with Prof. Charles Dinarello of the University of Colorado Denver. Novick, at the time a research associate in Rubinstein’s group, played a major role in this discovery.

 

Because of her genetic mutation, the baby’s body produced very high levels of an inflammatory molecule called interleukin-18 (IL-18). IL-18 was originally named “interferon gamma inducing factor,” and, like the more familiar interferon, it plays a critical role in our immune system, activating its T cells when disease-causing microbes invade. But if the body produces too much of it, the result can be inflammatory or autoimmune diseases. Novick and Rubinstein discovered that the body makes a natural “antidote” to IL‑18, which they named IL-18BP (for IL-18 binding protein).

 

Soo Hyun Kim, a research student in Rubinstein’s group, determined the structure of the IL-18BP gene and generated recombinant IL-18BP protein in quantities large enough to experiment with in animal models. In their experiments, the scientists discovered that this protein is normally produced in the human body in fairly high levels, and it targets IL-18 exclusively. This suggests that the protein is part of a normal immune cycle in which the immune T cells generate a response to infection, while substances such as IL-18BP simultaneously prevent an immune system overreaction.

 

High IL-18 levels are especially implicated in a number of autoimmune and inflammatory syndromes; thus, the researchers believe that treating patients with the body’s own “antidote” might not only alleviate the inflammation but also avoid harsh side effects. Animal model studies confirm this idea.

 

The doctors at the hospital in Philadelphia requested IL-18BP for compassionate use – that is, outside the scope of the clinical trial. This was agreed to and the US FDA promptly approved. After the baby returned home, the firm reported the following in a press release: “This is a major medical breakthrough confirming that our drug candidate is an effective and life-saving treatment for patients suffering from severe inflammatory diseases.”

 

IL-18 is overexpressed in more common autoimmune and inflammatory diseases, including lupus and Crohn’s disease, as well as heart disease and acute kidney injury. Since a simple blood test can reveal high levels of IL-18, Novick is hopeful that IL-18BP may eventually be used to treat multiple conditions for which there are no cures today.

 

IL-18BP adds to a list of ten other naturally occurring proteins that Novick has had a part in isolating. Her original source? Normal human urine, which, according to Novick, is a “goldmine.” These proteins include the soluble TNF Receptor II (TNF binding protein II or TBPII), which was translated into a drug for rheumatoid arthritis, and the type I interferon receptor, which had been sought for many years. Moving basic research from bench to bedside is, in most cases, a dream that can take decades to realize. Novick’s dream became reality in several projects. These include work she conducted with Rubinstein on interferon alpha, which resulted in the drug Roferon A™; her work on interferon beta with Prof. Michel Revel, which eventually resulted in the drug Rebif™ for the treatment of multiple sclerosis; research with Prof. David Wallach that translated into the drug Enbrel™ for rheumatoid arthritis; and now, IL-18BP, which saved a baby’s life and is currently in Phase II clinical studies. Novick is presently taking part in a project aiming to treat brain trauma and glioblastomas; the project is based on ideas developed by the late Prof. Vivian Teichberg and is now being pursued by Prof. David Mirelman.