JAK1/2 as a Central Regulator of iMCD Pathogenesis and Novel Therapeutic Target
Awardee: David Fajgenbaum
Institution: University of Pennsylvania
Award Amount: $64,590
Funding Period: February 1, 2021 - January 31, 2022
Summary: Idiopathic multicentric Castleman disease (iMCD) is a poorly understood disease involving life-threatening immune hyperactivation and cytokine production (a cytokine storm). About 1500 patients of all ages are diagnosed in the US each year and there is a 35% 5-year mortality rate. Siltuximab, which inhibits a key cytokine involved in the immune hyperactivation in iMCD, is the only FDA-approved therapy and is effective in one-third of patients. Dr. Fajgenbaum’s lab in the Center for Cytokine Storm Treatment and Laboratory (CSTL) recently identified another key mechanism of immune hyperactivation in iMCD called JAK/STAT that may be a promising target to direct treatments at. Through the Orphan Disease Center's grant, the CSTL is studying JAK/STAT in iMCD lymph node samples and the role of JAK inhibition as an iMCD treatment. If promising, the CSTL will develop a protocol for a proof-of-concept clinical trial of a JAK inhibitor (ruxolitinib) in iMCD patients. These studies will improve understanding of iMCD biology and may translate into more effective therapies.