Members of the Every Cure team have made significant strides over the last 15 years in advancing 21 repurposed treatments for conditions such as idiopathic multicentric Castleman Disease (iMCD), angiosarcoma, and COVID-19. See below for more information about these repurposed treatments. Every Cure is working towards identifying and advancing 15-25 more repurposed treatments by 2030. Check back here for updates on repurposing opportunities that we are advancing.
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This approach means that we don’t just hope that the right study will be conceptualized and applied for by a researcher. We identify the right study and then recruit the right researcher with the right skill set to perform the study and provide the necessary funding and tissue samples. Most importantly, any idea can potentially turn into a study rather than just ideas conceived by the researchers that can perform the studies.
After selecting the top priority project , recruiting the foremost expert in that field , and obtaining the necessary funds and samples, Every Cure assists with all aspects of successful execution of the study.
We establish a research agreement, coordinate contracts among collaborators, provide project management support, and contribute scientific advice throughout the process.
For every study, Every Cure works with patients and physicians around the world to coordinate obtaining the necessary samples (e.g., blood, saliva, left over lymph node tissue, etc). Obtaining high-quality samples is a major challenge in rare disease research.
Every Cure proactively seeks to obtain tissue samples for future studies, because researchers can’t do research without patient samples. Every Cure international community of researchers needs samples from patients so that we can continue to drive forward our search for a cure! These samples help us to better characterize this disease and will lead to greater knowledge about current and potential treatments.
After performing the studies and publishing the data, Every Cure works to ensure these findings are disseminated among researchers, physicians, patients and loved ones around the world as quickly as possible. We accomplish this through physician/researcher meetings, Patient Summits, online portals for patients, physicians and researchers, social media and online Every Cure resources.
When battling a rare disease, it is essential new findings are shared with a wide audience as quickly as possible.
Then,Every Cure shares these results with the medical community to inspire new ideas for research and the cycle repeats.
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Repurposing Analysis
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Identify Target
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Match to Drug
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Pre-Clinical Validation
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Treat/Track Patients
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Clinical Trial
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Treatment Guidelines
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Widespread Use
Leader(s): Dr. Chip Chambers, DADA2 Foundation
Key Publications:
Coarsi R et al. Long-term efficacy of etanercept in ADA2 deficiency
Mutant Adenosine Deaminase 2 in a Polyarteritis Nodosa Vasculopathy
Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2
About:
Deficiency of Adenosine Deaminase 2 (DADA2) is a rare and life-threatening genetic disorder characterized by inflammation, and blood vessel damage, and progressive strokes. Etanercept, a TNF inhibitor approved for the treatment of multiple autoimmune diseases was identified as a potential repurposed treatment for DADA2 by X (lets share some of the story). Treatment of DADA2 patients with etanercept has been groundbreaking, leading to improvements in clinical symptoms and a reduction in deadly strokes. Based on the role of etanercept as a life-saving treatment for DADA2 and evidence of its long-term efficacy from observational studies (Coarsi R et al.’s study; no clinical trials were performed), treatment guidelines were developed by Dr. Chip Chambers and the DADA2 Foundation (Lee P et al.’s international consensus statement) with guidance and support from Dr. David Fajgenbaum
Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum Kazu Yoshizaki, Castleman Disease Collaborative Network
Key Publications:
Yoshizaki K et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease
About:
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. In 1989, Yoshizaki et al discovered that interleukin-6 was a key cytokine in iMCD. This breakthrough led to the development of targeted therapies against IL-6 signaling, including tocilizumab, an anti-IL-6 receptor therapy. Concurrently, Janssen repurposed an anti-IL-6 therapy (siltuximab) that was initially developed for multiple myeloma and tested its efficacy in iMCD. A Phase II clinical trial resulted in the regulatory approval of siltuximab for iMCD, marking a significant milestone in the treatment of this rare disease. Following this, a Phase IV study was conducted by Dr. David Fajgenbaum at the University of Pennsylvania and Castleman Disease Collaborative Network to address a conditional approval requirement by the European Medicines Agency (EMA). Reflecting its established role in iMCD management, siltuximab is now recommended as a first-line treatment for iMCD in clinical guidelines.
Leader(s): Charles Vite, UF College of Veterinary Medicine
Key Publications:
Geberhiwot T et al. Consensus clinical management guidelines for Niemann-Pick disease type C
About:
Niemann-Pick disease type C (NPC) is a rare progressive genetic disorder characterized by an inability of the body to transport cholesterol and other fatty substances (lipids) inside of cells. Miglustat, originally developed for Gaucher disease, has been repurposed as a therapeutic option for NPC based on its ability to inhibit glucosylceramide synthase, potentially reducing the buildup of glycosphingolipids that contribute to the pathology of NPC. Co-Founder Tracey Sikora’s first experience with drug repurposing began with a 2012 paper in the Journal of Neuropathology & Experimental Neurology studying this drug-disease pair. Since, miglustat has been included in NPC clinical guidelines.
Leader(s): Dr. Martin Landray, University of Oxford
Key Publications:
The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19
About:
At the onset of the COVID-19 pandemic in early 2020, the medical community was grappling with a novel and rapidly spreading virus with no known treatments. Initially, based on the mixed results from prior studies on the role of corticosteroids in treating viral illnesses, the use of corticosteroids for COVID-19 was generally recommended against. However, a turning point came when Fajgenbaum et al. undertook the CORONA Project, a comprehensive initiative to track and analyze the use of various treatments against COVID-19 globally. In their report, published in Infectious Diseases & Therapy in 2020, they noted the widespread use of corticosteroids and highlighted potential benefits despite prior recommendations to the contrary. The empirical evidence for the efficacy of corticosteroids, particularly dexamethasone, was further solidified by the RECOVERY randomized controlled trial (RCT) conducted in the UK, which reported a significant reduction in mortality among hospitalized COVID-19 patients, especially those requiring oxygen. The results of this landmark study were published in the New England Journal of Medicine in 2021. In light of these findings, dexamethasone has become widely recommended for the management of COVID-19 in hospitalized patients, particularly for those on supplemental oxygen, marking a major update in the treatment guidelines and offering a glimmer of hope in the fight against the pandemic.
Leader(s) : Simran Sindhu, University of Arizona
Key Publications:
Sindhu S et al. Angiosarcoma treated successfully with anti-PD-1 therapy – a case report.
von Mehren M et al. Soft Tissue Sarcoma, Version 2.2022
About:
Angiosarcoma (AS) is a cancer that forms in the lining of blood vessels and lymph vessels. In 2016, metastatic angiosarcoma was considered a uniformly fatal condition, but the promise of PD1 inhibitors in cancer therapy was beginning to be recognized. A key development was reported by Kim in PLOS ONE in 2013, highlighting increased PDL1 staining, which is significant since PDL1 is a target for PD1 inhibitors. Despite these findings, there had been no recorded instances of AS patients being treated with any approved PD1 inhibitors such as pembrolizumab, which was initially approved for melanoma. Addressing this gap, Fajgenbaum and his team confirmed increased PDL1 staining in an AS patient and, in a pioneering approach, treated an AS patient with the PD1 inhibitor pembrolizumab, in 2016—a treatment strategy that had not been previously reported for this condition. Remarkably, by 2023, the initial patient remained alive and well, and several more patients had been treated successfully with this method. The promising outcomes have since initiated multiple clinical trials investigating PD1 inhibitors for AS, leading to the recommendation of PD1 inhibitors for AS in NCCS Guidelines marking a significant shift in the treatment paradigm for this aggressive cancer.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
Arenas D et al. Increased mTOR activation in idiopathic multicentric Castleman disease.
About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition, with existing treatments proving effective in only 34-50% of patients. The identification of mTOR as a novel therapeutic target through serum proteomics, as reported by Fajgenbaum in the Journal of Clinical Investigation. In 2014, Fajgenbaum became the first Castleman patient ever to take sirolimus, an FDA-approved mTOR inhibitor, which was initially approved for organ transplant rejection. Further validation came from immunohistochemical studies by Arenas in Blood, 2020, which confirmed heightened mTOR activation in iMCD tissues. This led to the launch of an NIH-funded clinical trial in 2019, with Pfizer donating the sirolimus for the study, reflecting a collaborative effort towards a potential new standard of care. In recognition of these developments, iMCD treatment guidelines were updated in 2018 to include sirolimus as a recommended therapy, as published by van Rhee in Blood, underscoring the integration of targeted therapy into clinical practice for iMCD management.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
About
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. A significant step forward was made when a study published in Lancet Haematology in 2016 identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target. Rituximab, known as an FDA-approved multiple myeloma drug for depleting B cells, was thereby considered for iMCD treatment. While in vitro studies to validate this approach are still in progress, retrospective evaluations of iMCD patients treated with rituximab, reported in the Annals of Hematology in 2018, have provided some empirical support. Despite the lack of dedicated clinical trials for rituximab in iMCD, its inclusion as a second-line therapy in the iMCD treatment guidelines, offering hope for a segment of the patient population previously limited by the efficacy of available treatments.
Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum Kazu Yoshizaki, Castleman Disease Collaborative Network
Key Publications:
Yoshizaki K et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease
Zhang M et al. UCD with MCD-like inflammatory state: surgical excision is highly effective
About:
Unicentric Castleman disease (UCD) is a subtype of Castleman Disease which involves a single enlarged lymph node or multiple enlarged lymph nodes within a single lymph node station. In 1989, Yoshizaki et al discovered that interleukin-6 was a key cytokine in Castleman. This breakthrough led to the development of targeted therapies against IL-6 signaling, including tocilizumab, an anti-IL-6 receptor therapy. Evidence from a 2021 study in Blood Advances we collaborated on identified cases of UCD with an MCD-like inflammatory state which suggested common biological behavior. As such, while siltuximab has been traditionally utilized first-line in the treatment of iMCD, it has been identified as a potential treatment for investigation in the context of unresectable unicentric Castleman disease (UCD) and added to international evidence-based guidelines.
Leader(s): Drs. David Fajgenbaum and Fritz van Rhee, Castleman Disease Collaborative Network
Key Publications:
About:
Unicentric Castleman disease (UCD) is a subtype of Castleman Disease which involves a single enlarged lymph node or multiple enlarged lymph nodes within a single lymph node station. Rituximab has demonstrated potential in iMCD as a second- and third-line treatment and is actively used in cases of iMCD where siltuximab is ineffective or unable to be utilized. However, it is being actively investigated as a therapy in the setting of unresectable UCD and discussed in corresponding international evidence-based guidelines for UCD by an expert committee convened by the Castleman Disease Collaborative Network.
Leader(s): Drs. Yu-jun Dong and David Fajgenbaum, Castleman Disease Collaborative Network
Key Publications
Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
Fajgenbaum D. HHV-8-negative/idiopathic multicentric Castleman disease UpToDate Guidelines
About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition, with existing treatments proving effective in only 34-50% of patients. In the quest for effective treatments for iMCD, the identification of autoantibodies suggested B/plasma cells as potential targets, as reported in Lancet Haematology in 2016. This insight led to the consideration of Velcade (bortezomib), a plasma cell inhibitor, as part of a combination therapy with Cytoxan (cyclophosphamide) and dexamethasone, known as VCD, which was initially approved for multiple myeloma. While in vitro studies are still confirming this approach, sporadic literature reports and a clinical trial by Zhang et al in Leukemia & Lymphoma in 2022 have highlighted improvements in iMCD patients treated with VCD. VCD has been formally adopted into iMCD treatment UpToDate guidelines.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review
Fajgenbaum D. HHV-8-negative/idiopathic multicentric Castleman disease UpToDate Guidelines
About
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. The exploration of treatments for iMCD took a significant turn with the discovery of autoantibodies in iMCD patients, highlighting B cells and plasma cells as promising targets. This finding, reported by Liu in Lancet Haematology in 2016, paved the way for investigating thalidomide, a plasma cell modulator, as part of the TCP regimen, which also includes Cytoxan (cyclophosphamide) and prednisone. This regimen was initially approved and utilized in multiple myeloma. While full validation of this therapeutic approach is still underway, anecdotal evidence from the medical literature suggests some iMCD patients have benefited from TCP therapy. Empirical support for TCP’s efficacy was further provided by a clinical trial conducted by Zhang et al, published in Blood in 2019, which reported patient improvements. TCP has been formally adopted into iMCD treatment UpToDate guidelines.
Leader(s): Dr. David Fajgenbaum, Castleman Disease Collaborative Network
Key Publications:
About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition, with existing treatments proving effective in only 34-50% of patients. The discovery of the JAK/STAT pathway as a key therapeutic target for idiopathic multicentric Castleman disease (iMCD), as highlighted in Pierson’s 2021 study in Blood Advances, marked a pivotal advance in treatment research. This led to ruxolitinib, a JAK inhibitor initially approved for myelofibrosis, to be identified as a promising treatment for iMCD. This identification was supported by immunohistochemistry studies, also conducted by Pierson, which demonstrated increased JAK activation in iMCD tissues. Building on this foundation, Lust et al. reported in Pediatric Blood Cancer in 2021 the first use of ruxolitinib in iMCD patients, initiating a novel treatment approach. Concurrently, the Center for Cytokine Storm Treatment & Laboratory (CSTL) is spearheading the launch of a clinical trial in partnership with Incyte to further assess ruxolitinib’s effectiveness.
Leader(s): Professor Edward Mills TOGETHER Investigators, Angelo, CORONA Team
Key Publications
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During the early stages of the COVID-19 outbreak in 2019, the global medical community was in urgent search of treatments for the novel coronavirus. Amidst this, hyperinflammation was identified as a potential mechanism contributing to the high mortality rate associated with the virus. The connection between fluvoxamine and COVID-19 began to form when Rosen et al. published findings in Science Translational Medicine in 2019, revealing that fluvoxamine could modulate sigma-1 receptor (sigma-1R) activity which is associated with hyperinflammation. This discovery offered a potential pathway through which fluvoxamine could be repurposed to mitigate the severe inflammatory response seen in COVID-19. Following this revelation, pilot clinical trials were initiated to evaluate the efficacy of fluvoxamine in treating COVID-19 patients. Concurrently, the CORONA Project, utilizing a comprehensive algorithm, identified fluvoxamine as a promising candidate and advocated for its inclusion in the National Institutes of Health’s (NIH) ACTIV-6 trial, a platform designed to test a variety of repurposed drugs. Further evidence supporting the use of fluvoxamine came from a 2022 publication in The Lancet. The TOGETHER trial, a randomized platform clinical trial, evaluated the effect of early treatment with fluvoxamine on reducing the risk of requiring emergency care and hospitalization among patients with COVID-19. The results of this trial provided crucial clinical data, bolstering the case for fluvoxamine as a potentially beneficial treatment for reducing severe outcomes in COVID-19 patients.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
Wing A et al. Transcriptome and unique cytokine microenvironment of Castleman disease
About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition, with existing treatments proving effective in only 34-50% of patients.In a significant advance in finding treatments for iMCD, Pierson’s serum proteomics research highlighted complement activation, including C5, as a novel therapeutic target. This led to the identification of eculizumab, a C5 inhibitor initially approved for Myasthenia Gravis. Validation through transcriptomics by Wing underscored this pathway’s role in iMCD. Moving from theory to application, the first group of iMCD patients received eculizumab in 2020, with their progress being documented in the University of Pennsylvania’s patient registry.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications
About
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. The potential use of adalimumab for iMCD first arose from serum proteomic studies by Pierson, published in Blood Advances in 2021, which highlighted TNF as a novel therapeutic target. Adalimumab, an anti-TNF agent which is FDA-approved for conditions such as Rheumatoid Arthritis, emerged as a potential treatment for iMCD. While formal validation studies are pending, the initial application of adalimumab in iMCD patients began in 2023 which was recently published as an ASH conference abstract. Despite the absence of a clinical trial to rigorously assess its efficacy in iMCD, these preliminary treatments represent a forward step in exploring adalimumab’s role in managing this severe disease.
Leader(s): Dr. Frits van Rhee David Fajgenbaum, Castleman Disease Collaborative Network
Key Publications
Khan M et al. Daratumumab for POEMS Syndrome
About
The exploration of novel treatments for POEMS syndrome, a rare paraneoplastic disorder associated with plasma cell dyscrasia, has led to interest in targeting specific cellular pathways. Daratumumab, a monoclonal antibody against CD38, known as an FDA-approved agent for multiple myeloma, has emerged as a potential therapy for POEMS syndrome. Recently, a patient was getting ready to go onto hospice care until daratumumab was administered ultimately saving his life. This places daratumumab in the early stages of investigation within the context of POEMS Syndrome, with significant research and clinical testing required to establish its efficacy and safety for this new indication.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
Yoshimi A et al. Genetic basis for iMCD-TAFRO
About
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition, with existing treatments proving effective in only 34-50% of patients. The potential use of Trametinib for iMCD took a promising turn with the identification of a MEK2 mutation through genomic sequencing by Yoshimi in Oncogene, 2020. Trametinib, a MEK inhibitor already approved by the FDA for melanoma, aligned as a potential treatment, showing encouraging responses in subsequent in vitro studies. However, the path from research to clinical application remains to be charted, as trametinib has not yet been used to treat iMCD patients, leaving a significant opportunity for future exploration and validation in a clinical setting.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
Phillips A et al. Increased mTORC2 pathway activation in lymph nodes of iMCD-TAFRO
About:
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. A new treatment for idiopathic multicentric Castleman disease (iMCD) occurred with the identification of activation of both mTORC1 and mTOR2 pathways in iMCD, as revealed by immunohistochemistry (IHC) in research by Phillips published in the Journal of Clinical and Cellular Immunology in 2022, directed attention to a new potential therapeutic target. Sapanisertib, an inhibitor of both mTORC1 and mTOR2 and initially approved for Squamous Lung Cancer was targeted as a potential therapeutic agent for iMCD. The journey of sapanisertib from a promising theoretical match to a validated treatment option is still in the preliminary stages.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
About:
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. The potential use of anifrolumab for idiopathic multicentric Castleman disease (iMCD) represents a novel approach, building on the foundational work of Pai et al., who identified interferon-alpha (IFNa) as a promising therapeutic target in their 2020 publication in JCI Insight. Anifrolumab, an anti-IFNa agent originally developed for systemic lupus erythematosus (SLE), has thus been pinpointed as a potential therapeutic option for iMCD. This repositioning of anifrolumab from SLE to iMCD treatment is based on the shared mechanism of targeting IFNa, suggesting that the immunomodulatory effects of anifrolumab could be beneficial in the context of iMCD’s pathophysiology. However, the application of anifrolumab in iMCD is still in the conceptual phase, with further research needed to validate its effectiveness and safety for iMCD patients.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
About:
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. Emapalumab’s exploration as a potential treatment for iMCD stems from Mumau’s abstract presented at the 2022 American Society of Hematology (ASH) conference suggesting that interferon-gamma (IFNy) could be a viable therapeutic target for iMCD. This finding pivoted attention towards emapalumab, an anti-IFN-gamma therapy initially developed for hemophagocytic lymphohistiocytosis (HLH), as a promising candidate for iMCD treatment due to its mechanism of action. This places emapalumab in the early stages of investigation within the context of iMCD, with significant research and clinical testing required to establish its efficacy and safety for this new indication.
Leader(s): Dr. David Fajgenbaum, University of Pennsylvania
Key Publications:
Pierson S et al. CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease.
About:
Idiopathic multicentric Castleman disease is a rare and deadly cytokine storm disorder that occurs for an unknown cause. A new insight for effective treatments for iMCD occurred when serum proteomics pinpointed CXCL13 as a novel therapeutic target as published in Nature Communications by Pierson in 2022. This discovery led to the identification of anti-CXCL13/CXCR5 drugs that were initially approved for rheumatoid arthritis as potential treatments for iMCD. Preliminary evidence supporting the efficacy of these treatments came from a xenograft mouse model of iMCD, which showed improved survival following CXCL13 inhibition, with these findings currently under review for publication. This progress represents a hopeful advancement in the development of targeted therapies for iMCD, potentially offering new avenues for treatment where previous options were limited.
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