- Drug Repurposing
The Center for Cytokine Storm Treatment & Laboratory (CSTL) and the Castleman Disease Collaborative Network (CDCN), under the leadership of Dr. David Fajgenbaum, are committed to the discovery of new uses for existing drugs to save patients’ lives. There are ~1,500 drugs currently FDA approved to treat ~2,500 of the ~10,000 human diseases. No treatments exist for over 7,000 diseases, many of which are rare and deadly.
The CSTL and CDCN have pioneered the following approach to drug repurposing for idiopathic multicentric Castleman disease (iMCD) and other rare diseases: 1) perform in-depth studies of high-quality biospecimens to identify cell types, signaling pathways, and genes/proteins that may be involved in a given disease, 2) validate the discovery using an orthogonal method, 3) utilize bioinformatic tools and drug databases to identify drugs already FDA-approved for another condition that modulate the target, 4) administer the drug off-label (giving a drug for a use other than what it is approved for) or through a clinical trial, and 5) systematically track the impact of the drug on the given disease.
This approach has led to the discovery and clinical development of two drugs for the treatment of iMCD. Dr. Fajgenbaum, also a patient with iMCD, began testing one of these drugs on himself in 2014 and is in his longest remission ever (more here). The CSTL opened up a clinical trial of this drug last fall. For more about this approach, check out this video.
CORONA (COvid Registry of Off-label & New Agents)
Given the global crisis occurring due to COVID19 and the urgent need to identify effective therapeutics, the heightened risk of COVID19 to Castleman disease patients and other patients with immunological disorders and immunocompromise, and the CSTL’s expertise regarding drug repurposing, the CSTL has begun directing efforts toward fighting COVID19 (while maintaining focus and efforts on our other high-priority studies.)
Our overarching vision: A world where data on all treatments that have been used against COVID19 are stored in a central, high-quality database and analyzed so that physicians currently treating COVID19 patients know what treatments are most likely to help their patients and so that clinical trials can be appropriately prioritized.
Phase 1: COMPLETED
Our team reviewed 2500+ papers & extracted data on over 9,000 COVID19 patients from published papers on PubMed and archive databases. We found 115 repurposed drugs that have been used for COVID19 and analyzed data on which ones seem most promising for clinical trials. This data is open source and can be used by physicians to treat patients and prioritize drugs for trials. The CDCN will keep this database updated as a resource for this global fight. In parallel, we are re-analyzing and identifying trends across research studies to create a COVID19 Immune Map to dissect the immune response to COVID19 that could guide therapeutic decisions. Repurposed drugs give us the best chance to help COVID19 as quickly as possible!
Read our systematic literature review published in Infectious Diseases and Therapy at the following link: Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review
Read the Press Release from PennMedicine at the following link: PennMedicine Press Release
Phase 2: Continue to update CORONA
Our team continues to work diligently to maintain an updated listing of all treatments reported to be used in COVID19 patients from papers in PubMed. We are also re-analyzing publicly available COVID19 single cell transcriptomic data alongside our iMCD data to search for novel insights and therapeutic targets.
You can visit the following link to access a database viewer built and managed by Matt Chadsey, owner of Nonlinear Ventures: COVID19 Drug Repurposing Database Viewer
If you are a physician treating COVID19 patients, please visit the FDA's CURE ID app to report de-identified information about drugs you've used to treat COVID19 in just a couple minutes.
Click here for up-to-date treatment guidelines from the NIH.
Check out the following links for more information about CORONA:
Dr. Fajgenbaum describing the CORONA project on Fresh Air.
Dr. Fajgenbaum describing the CORONA project on 6ABC.
Dr. Fajgenbaum describing the CORONA project on KTLA.
Dr. Fajgenbaum describing the CORONA project on FOX5.
Dr. Fajgenbaum describing the CORONA project on ABC7.
Dr. Fajgenbaum describing the CORONA project on WRAL.
CORONA project highlighted in the Boston Globe.
CORONA project highlighted by Diane Sawyer on 20/20.
CORONA project highlighted by CNN.
The CDCN is proud to be joining the fight against COVID19. Check out this video to learn how the CDCN is helping in the fight against COVID19!
You can email email@example.com if you are interested in contributing to this project by reviewing through published papers and extracting out information about drugs being used to treat COVID19.
Or, if you’d prefer, you can donate to support and enable this critical work at: https://cdcn.org/join-the-fight/donate/
We are grateful to our Phase I team members who have taken on this urgent need:
David Fajgenbaum, CSTL Director
Johnson Khor, CSTL Coordinator and COVID19 Project Lead
Sheila Pierson, CSTL Clinical Research Director
Ruth-Anne Langan, UPenn PhD Student and COVID19 Data Analyst
Alek Gorzewski, ACCELERATE Data Analyst and COVID19 Data Analyst
Mark-Avery Tamakloe, ACCELERATE Data Analyst and COVID19 Data Analyst
Tori Powers, ACCELERATE Data Analyst and COVID19 Data Analyst
Rozena Rasheed, CastleBank Coordinator and COVID19 Data Analyst
Mileva Repasky, CDCN Chief Patient and Development Officer and COVID19 Data Analyst
Bruna Martins, Medidata Global Digital Marketing Manager and COVID19 Data Analyst
Eric Rodrígues-López, UPenn PhD Student and COVID19 Data Analyst
Joseph Kakkis, UPenn BS Candidate and COVID19 Data Analyst
Madison McCarthy, Brown University BS Candidate and COVID19 Data Analyst
Anne Taylor, OSU MD Candidate and COVID19 Data Analyst
Erin Napier, University of Hawaii MD Candidate and COVID19 Data Analyst
Lia Keyser, Brown University BA Recipient and COVID19 Data Analyst
Dr. Duncan Mackay, PennMedicine Physician and COVID19 Data Analyst
Alex Beschloss, UPenn MD Candidate and COVID19 Data Analyst
Anna Wing, UPenn MD Candidate and COVID19 Data Analyst
Ashwin Amurthur, UPenn MD Candidate and COVID19 Data Analyst
Beatrice Go, UPenn MD Candidate and COVID19 Data Analyst
Casey Kim, UPenn MD Candidate and COVID19 Data Analyst
James Germi, UPenn MD Candidate and COVID19 Data Analyst
Joanna Jiang, UPenn MD Candidate and COVID19 Data Analyst
Laura Miyarnes, UPenn MD Candidate and COVID19 Data Analyst
Michael Mayer, UPenn MD Candidate and COVID19 Data Analyst
Philip Angelides, UPenn MD Candidate and COVID19 Data Analyst
Sarah Frankl, UPenn MD Candidate and COVID19 Data Analyst
Vivek Nimgaonkar, UPenn MD Candidate and COVID19 Data Analyst
Steve Bambury, University of Pittsburgh BS Candidate and COVID19 Data Analyst
Nick Goodyear, Temple University BS Candidate and COVID19 Data Analyst
Megan Fisher, Georgetown University BS Candidate and COVID19 Data Analyst
Karen Gunderson, Physician Assistant and COVID19 Data Analyst
We are grateful to our Phase II team members who have continued this important work:
Alex Beschloss, Anne Taylor, Ashwin Armurthur, Aura Enache, Beatrice Go, Biliana Rotse, Bruna Martins, Cheng Cheng, David Bright, Derek Ansel, Dorothy Kenny, Edward Shadiack, Evaggelia Nassis, Florence Porterfield, Gary Gravina, Hadis Williams. Heather Farley, Helen Eisenach, James Germi, Jayson Wisk, Jenna Pacheco, Joanna Jiang, Joseph Kakkis, Joshua Deffenbaugh, Karen Gunderson, Kate Chang, Kevin Freiert, Kristen Stegeland, Lindsay Muratore, Maggie Reilly, Margareta Sorenson, Matt Pepper, Megan Fisher, Meggie Goodridge, Meryt Hanna, Monica Lucurara, Nicole Engelhardt, Philip Angelides, Philip Rybczynski, Sarah Frankl, Sarah VanFleet, Shah Makujina, Trisha Paryil, Vivek Nimgaonkar