I’m so proud of my team at the University of Pennsylvania’s Center for Study & Treatment of Lymphadenopathies & Cytokine Storms. Today, five years worth of research into mechanisms involved in the idiopathic multicentric Castleman disease (iMCD) cytokine storm, which has major implications for other cytokine storms like COVID19, were published in two high-impact journals.
Our paper in the journal Blood extended our findings from our 2019 Journal of Clinical Investigation paper revealing mTOR as a therapeutic target in the iMCD cytokine storm and reporting the effectiveness of sirolimus in three patients (I was patient #1). In this study, we also uncovered a potential new therapeutic target (JAK1/2). Daniel Arenas did an amazing job leading this project! Click here for the full text.
In our paper in the Journal of Clinical Investigation Insight, we performed flow cytometry and single cell RNAseq to characterize and dissect what is happening in the peripheral blood of patients during an iMCD cytokine storm. We found increased T cell activation, decreased CD16 expression on monocytes/NK cells, and a strong Type I Interferon (IFN-I) signature. Interestingly, these features have recently been observed in similar studies of COVID19. We also found that the IFN-I-stimulated mTOR hyperactivation can be abrogated with JAK1/2 inhibition, further supporting JAK1/2 inhibition as a potential new therapeutic approach. Ruth-Anne Pai did an amazing job leading this project and performing the various assays. Click here for the full text.
It feels really good knowing that we connected on two punches at iMCD today, and it feels just as good knowing that these punches are also helping to understand how to better treat COVID19.
David Fajgenbaum, MD, MBA, MSc, is a groundbreaking physician-scientist, disease hunter, speaker, and bestselling author of the acclaimed memoir, Chasing My Cure: A Doctor’s Race to Turn Hope Into Action. Best known as the ‘doctor who cured himself’ (Doctor Cure Thyself, NY Times), Fajgenbaum went from being a beast-like college Quarterback to receiving his last rites while in medical school and nearly dying four more times battling Castleman disease. To try to save his own life, he spearheaded an innovative approach to research and discovered a possible treatment that has put him into an extended remission. Now, he is spreading this approach to other diseases (His method could save millions, CNN) and sharing lessons he learned about living from nearly dying through Chasing My Cure, which has been translated into five languages and named one of the “Best Non-Fiction Books of 2019” by Next Big Ideas Club.