Grants Awarded

Principal Investigator
Kim E. Nichols, MD
University of Pennsylvania Perelman School of Medicine
The Children’s Hospital of Philadelphia – Philadelphia, Pennsylvania USA

Date of Award
December 2013

Amount of Award
$50,000

Layperson Summary
Hemophagocytic lymphohistiocytosis (HLH) is a rare and poorly understood group of diseases affecting the immune system. Children with HLH experience excessive build-up and activation of various types of white blood cells within their organs, including the liver, brain and bone marrow. If not properly recognized and treated, HLH can damage the organs and lead to death. Currently, the treatment for HLH is aimed at quieting down the over-active immune system with immunosuppressive drugs, such as steroids and chemotherapy medications. While this approach is effective in some patients, these drugs exhibit significant side effects and less-than-optimal results. Consequently, the death rate for HLH is high and measures up to 50%. To win the battle against HLH, we need to think “outside of the box” and come up with better ways to beat this disorder.

In this Histiocytosis Association proposal, we plan to test whether a new class of drug known as a “JAK inhibitor” is more effective as a treatment for HLH. The JAK inhibitors work by blocking the effects of chemicals known as “cytokines” on the cells of the body. Under normal circumstances, activated immune cells secrete cytokines to help protect against infection. However, in HLH, activated immune cells secrete very high levels of certain cytokines that are actually harmful to the body. We believe that the JAK inhibitors will be good medications for HLH patients because they provide a new way to dampen cytokine-driven inflammation. In support of this notion, we find that a JAK inhibitor known as “ruxolitinib” decreases the signs of disease in mice with HLH. To determine whether ruxolitinib or other JAK inhibitors will be effective as a treatment for HLH, we will treat mice that have various forms of HLH with different JAK inhibitors and see if this reduces the signs of inflammation. If these studies are successful, they will provide us with important information so that we can design a clinical trial to test whether the JAK inhibitors are similarly helpful for children or adults with HLH. Ruxolitinib and some of the other JAK inhibitors are already FDA-approved and known to be safe in adults. Therefore, we expect that it will be very straightforward to test the effects of these drugs in patients with HLH.