The use of a beta blocker is being investigated by Every Cure as a potential therapy for a rare neurodegenerative disease. Early evidence suggests the drug may benefit patients by enhancing lysosomal function. We are conducting preclinical studies to validate these mechanisms and evaluate real-world evidence supporting its potential impact.

Every Cure is exploring the use of an epigenetic modifier to improve outcomes in a muscle degenerative disorder. Early preclinical evidence suggests this strategy may enhance the effectiveness of existing therapies when used in combination. We are conducting additional preclinical studies to evaluate feasibility, clarify dosing considerations, and potential for meaningful benefit.

Every Cure is exploring the use of an antifibrotic therapy as a potential treatment for a rare pediatric multisystem disorder. Building on evidence of antifibrotic activity across multiple diseases, we are conducting preclinical studies to evaluate this approach’s potential to reduce fibrosis and improve outcomes in disease models.

Every Cure is exploring the use of an approved oral therapy as a treatment for a rare pediatric neurological condition. We are conducting early preclinical studies to evaluate whether this drug’s secondary pharmacological activity could address the underlying genetic mechanism of the disease and help determine whether the opportunity warrants further development.

The use of a metabolism-modifying therapy for a progressive fibrotic lung disease is an active program at Every Cure. Building on preclinical models and real-world evidence, we are working to strengthen the clinical evidence by supporting ongoing and planned clinical studies.

Every Cure is advancing the use of an immune-modulating therapy for a rare vascular malignancy. Evidence from published case reports suggests meaningful clinical activity, and we are establishing the feasibility of a prospective clinical study to test this hypothesis.

The use of an angiotensin receptor blocker for a rare blistering disorder is an active program at Every Cure. Building on multiple in vitro studies, a phase I/II trial, and a case series, we are working to strengthen the clinical evidence in order to help more patients with this painful condition.

Every Cure is investigating the use of an mTOR inhibitor for an inflammatory granomatous disease. We are exploring a prospective clinical trial to fill existing evidentiary gaps and move this repurposing opportunity closer to real world use.

Every Cure is advancing the use of an amino acid for a rare mitochondrial disease. We aim to build on the existing strong mechanistic rationale and early clinical signals with real-world evidence studies, assay development,and clinical research.

Every Cure is investigating the use of sirolimus as a potential treatment for a rare neurocutaneous disorder called Sturge-Weber syndrome (SWS). Building on encouraging early clinical data, we are supporting a multicenter longitudinal registry to better understand long-term outcomes and generate the evidence needed to guide patient care.

Program under development. Details to be added when available.

Every Cure is collaborating with the researchers who first identified Bachmann-Bupp Syndrome (BABS), Dr. Andre Bachmann of Michigan State University, College of Human Medicine and Dr. Caleb Bupp of Corewell Health, on a repurposing opportunity with the drug DL-alpha-difluoromethylornithine (DFMO). BABS is a rare, genetic disorder that causes symptoms including neurodevelopmental delay, alopecia (hair loss), and hypotonia (poor muscle tone). DFMO (also known as eflornithine) has historically been used to treat African sleeping sickness and female facial hair growth, and it is currently approved for the prevention of recurrence of neuroblastoma. Building on encouraging off-label use and mechanistic experiments pioneered by Dr. Bachmann and Dr. Bupp, we aim to perform preclinical experiments further supporting the molecular underpinnings of this disease, a retrospective study of all identified patients to date, and prepare for a regulatory submission to bring this potential therapy to more children in need.

See key publications:

Improvement of dermatological symptoms in patients with Bachmann–Bupp syndrome using difluoromethylornithine treatment

Repurposing With Purpose: Treatment of Bachmann-Bupp Syndrome With Eflornithine and Implications for Other Polyaminopathies

Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation

Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features

Repurposing eflornithine to treat a patient with a rare ODC1 gain-of-function variant disease

Key Collaborators

• Dr. Andre Bachmann of Michigan State University, College of Human Medicine

• Dr. Caleb Bupp of Corewell Health

The use of lidocaine for breast cancer is an active program at Every Cure. Building on the foundational work of prior researchers, we are working to ensure that the doctors and surgeons who would administer this treatment are aware of the evidence and able to access it. In parallel, the team is exploring opportunities to strengthen the evidence base by verifying existing data and assessing the potential for additional preclinical research.

See key publication by Rajendra A. Badwe, MS, et al. 

Glabellar injection of Botox for major depressive disorder is an active program at Every Cure that builds on a foundation of over a dozen clinical studies showing a significant and clinically meaningful benefit.

See key publication

Every Cure is pursuing a repurposing opportunity for lenalidomide-dexamethasone in a rare histiocytosis condition called Rosai-Dorfman-Destombes disease (RDD). Building on evidence from a Phase II study and extensive case reports demonstrating safety and clinical benefit, we are working to raise awareness among clinicians and researchers about its potential for broader use in this rare disorder and to ensure that all patients who could benefit have access to the therapy.

See key publication and learn more. 

Key Collaborators

• Dr. Luke Chen of Dalhousie University

• Histiocytosis Association 

The use of calcium folinate for cerebral folate deficiency associated with speech and other neurodevelopmental delays was an active program at Every Cure. Building on the foundational work of prior researchers, we worked to ensure that individuals who may have cerebral folate deficiency were aware of the available evidence.

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Lead Investigator: Dr. David Fajgenbaum, University of Pennsylvania

Key Publications

Fajgenbaum D et al. Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6 blockade–refractory idiopathic multicentric Castleman disease

Arenas D et al. Increased mTOR activation in idiopathic multicentric Castleman disease.

Van Rhee F et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease

About:
Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction. Few treatment options existed in 2014. In 2014, Fajgenbaum identified mTOR as a novel therapeutic target through serum proteomics, flow cytometry, and immunohistochemistry and became the first Castleman patient ever to take sirolimus, an FDA-approved mTOR inhibitor, which was initially approved for organ transplant rejection. This discovery and the use of sirolimus in Dr. Fajgenbaum and two other patients was published in the Journal of Clinical Investigation. Fajgenbaum and his team performed additional studies to confirm heightened mTOR activation in other iMCD patients (Arenas et al, Blood, 2020). This led to the launch of an NIH-funded clinical trial and the inclusion of sirolimus in iMCD treatment guidelines.

Leader(s): Dr. Chip Chambers, DADA2 Foundation 

Key Publications:

Coarsi R et al. Long-term efficacy of etanercept in ADA2 deficiency

Cooray S et al. Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2)

Lee P et al. Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

About

Deficiency of Adenosine Deaminase 2 (DADA2) is a rare and life-threatening genetic disorder that primarily causes severe inflammation and damage to blood vessels leading to early strokes, but it can also present with immunodeficiency and bone marrow failure. By chance, doctors discovered that tumor necrosis factor (TNF) inhibitors—medications such as Etanercept, Adalimumab, and Infliximab, already approved for multiple autoimmune diseases—could be repurposed to treat DADA2. This breakthrough has been transformative: not a single patient treated with TNF inhibitors has suffered a stroke since starting therapy, an unprecedented result in rare disease care. Because the evidence is so strong, clinical trials were never conducted and likely never will be. Building on this discovery, treatment guidelines were developed by Dr. Chip Chambers and 38 world-wide experts on DADA2, together with the DADA2 Foundation, through an international consensus guidelines (Lee P. et al.) with support from Dr. David Fajgenbaum. Today, most patients with DADA2 worldwide are effectively treated with TNF inhibitors, giving them safer and healthier lives.

Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum, Kazu Yoshizaki, Castleman Disease Collaborative Network

Key Publications

Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review

Dong Y et al. Effectiveness of rituximab-containing treatment regimens in idiopathic multicentric Castleman disease

iMCD Guidelines

About

Idiopathic multicentric Castleman disease is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. Fajgenbaum and his team published a study in Lancet Haematology in 2016 that identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target and rituximab as a potential treatment. Fajgenbaum worked with collaborators to perform retrospective evaluations of iMCD patients treated with rituximab, revealing a role for rituximab which was reported in the Annals of Hematology in 2018. Despite the lack of dedicated clinical trials for rituximab in iMCD, rituximab was included as a second-line therapy in the iMCD treatment guidelines.

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

Van Rhee F et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease

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. While interleukin-6 (IL-6) has been known to play a key role in multicentric Castleman disease (MCD) for years, Fajgenbaum collaborated with Lu Zhang and colleagues in 2021 study in Blood Advances which identified cases of UCD with an MCD-like inflammatory state, suggesting common biological behavior and possibly a role for IL-6. Based on anecdotal data from siltuximab in unresectable UCD, Fajgenbaum and colleagues advocated for the inclusion of siltuximab in international evidence-based guidelines for unresectable UCD.

Leader (s): Drs. Frits van Rhee, Corey Casper, David Fajgenbaum, Kazu Yoshizaki, Castleman Disease Collaborative Network

Key Publications:

Van Rhee F et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease

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. Based on work done by Fajgenbaum and colleagues, rituximab in the setting of unresectable UCD was included in international evidence-based guidelines for UCD.

Leader(s): Dr. David Fajgenbaum, University of Pennsylvania 

Key Publications:

About: POEMS syndrome is a rare paraneoplastic disorder involving monoclonal plasma cells, debilitating neuropathy, and life-threatening multi-organ system dysfunction with limited treatment options. Carfilzomib-cyclophosphamide-dexamethasone is a treatment often used for multiple myeloma. Given the similarities between multiple myeloma and POEMS syndrome and a high score for these agents and related agents in an early version of Every Cure’s algorithms, carfilzomib-cyclophosphamide-dexamethasone was administered to a POEMS patient in January 2024 who was getting ready to go onto hospice care, which ultimately saved his life (NYT link here). In Summer 2024, this treatment approach was described by a separate group in a conference research article.

Lead Investigator: Drs. Lu Zhang, Jian Li (Peking Union University Medical Center), and David Fajgenbaum, University of Pennsylvania 

Key Publications

Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review

Zhang L et al. A prospective, multicenter study of bortezomib, cyclophosphamide, and dexamethasone in relapsed/refractory iMCD

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 involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. Fajgenbaum and his team published a study in Lancet Haematology in 2016 that identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target and 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. A clinical trial by Fajgenbaum and colleagues in Zhang et al (Leukemia & Lymphoma, 2022) highlighted improvements in iMCD patients treated with VCD. VCD has been included in UpToDate guidelines for iMCD treatment.

Lead Investigator: Drs. Lu Zhang, Jian Li (Peking Union University Medical Center), and David Fajgenbaum, University of Pennsylvania 

Key Publications

Liu A et al. Idiopathic multicentric Castleman’s disease: a systematic literature review

Zhang L et al. Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease

Fajgenbaum D. HHV-8-negative/idiopathic multicentric Castleman disease UpToDate Guidelines

About

Idiopathic multicentric Castleman disease is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. Fajgenbaum and his team published a study in Lancet Haematology in 2016 that identified the presence of autoantibodies in iMCD patients, implicating B cells as a potential therapeutic target and  thalidomide, a plasma cell modulator, along withCytoxan (cyclophosphamide) and prednisone (TCP regimen). This regimen was initially approved and utilized in multiple myeloma. A clinical trial performed by Fajgenbaum and colleagues (Zhang et al, Blood, 2019) reported patient improvement. TCP has been included in UpToDate guidelines for iMCD treatment.

Leader(s): Dr. Frits van Rhee and David Fajgenbaum, Castleman Disease Collaborative Network

Key Publications

Khan M et al. Daratumumab for POEMS Syndrome

About

POEMS syndrome is a rare paraneoplastic disorder involving monoclonal plasma cells, debilitating neuropathy, and life-threatening multi-organ system dysfunction with limited options. Given the important role that plasma cells play in POEMS syndrome and the fact that daratumumab, a monoclonal antibody against CD38 that is FDA approved for the treatment of multiple myeloma, is effective at eliminating plasma cells, Drs. van Rhee and Fajgenbaum decided to try daratumumab in a POEMS syndrome patient who responded well.

Leader(s): Drs. Frits van Rhee and David Fajgenbaum, Castleman Disease Collaborative Network 

Key Publications:

Van Rhee F et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease

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. After Fajgenbaum and colleagues demonstrated the potential of sirolimus in iMCD, they investigated its role in unresectable UCD, demonstrated its effectiveness in the first unresectable UCD patient treated, and included it in international evidence-based guidelines for UCD.

Lead Investigator: Dr. David Fajgenbaum, University of Pennsylvania 

Key Publications

Pierson S et al. Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease

Lust H et al. Idiopathic multicentric Castleman disease with TAFRO clinical subtype responsive to IL-6/JAK inhibition: A pediatric case series

About

Idiopathic multicentric Castleman disease (iMCD) is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. In 2021 Fajgenbaum and colleagues discovered that the JAK/STAT pathway is a key therapeutic target for iMCD, which was highlighted in Pierson et al, Blood Advances, 2021). This led to ruxolitinib, a JAK inhibitor initially approved for myelofibrosis, to be identified as a promising treatment for iMCD and the first iMCD patient treated with ruxolitinib (Lust et al, Pediatric Blood Cancer, 2021). Currently, the Center for Cytokine Storm Treatment & Laboratory (CSTL) is spearheading the launch of a clinical trial to further assess ruxolitinib’s effectiveness in iMCD.

Leader(s): Dr. David Fajgenbaum, University of Pennsylvania 

Key Publications

Pierson S et al. Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease

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 involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. In 2018, Fajgenbaum and colleagues discovered complement activation as a potential therapeutic target in iMCD (Pierson et al, AJH, 2018). This led to the identification of eculizumab, a C5 inhibitor initially approved for Myasthenia Gravis. A separate study also involving Dr. Fajgenbaum also identified a complement signature from transcriptomic analyses (Wing et al). Based on these findings, the first few iMCD patients were given eculizumab in 2020, with their progress being documented in the University of Pennsylvania’s Castleman disease patient registry.

Leader(s): Dr. David Fajgenbaum, University of Pennsylvania, and Luke Chen, UBC-Vancouver 

Key Publications

Pierson S et al. Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease

Mumau M et al. A Translational Approach to Identifying and Targeting TNF Signaling in Idiopathic Multicentric Castleman Disease

About

Idiopathic multicentric Castleman disease is a rare and potentially fatal hematologic condition involving systemic inflammation and life-threatening multi-organ system dysfunction with limited treatment options. In 2023, Fajgenbaum and colleagues combined together results from serum proteomics analyses, in vitro studies, and an early version of Every Cure’s AI platform to identify TNF as a novel therapeutic target. Adalimumab, an anti-TNF agent which is FDA-approved for conditions such as rheumatoid arthritis, was utilized in a highly treatment refractory patient, who has been in remission for over two years. This case was published in the New England Journal of Medicine. 

Lead Investigator(s): Jung Ryul Kim and Kyu Yun Jang, Chonbuk National University Medical School, Korea

Key Publications

Kim J et al. Tumor Infiltrating PD1-Positive Lymphocytes and the Expression of PD-L1 Predict Poor Prognosis of Soft Tissue Sarcomas

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 rare and deadly cancer that forms in the lining of blood vessels and lymph vessels. In 2016, metastatic angiosarcoma was considered a uniformly fatal condition. However, an important study was performed by Kim (PLOS ONE, 2013) on five AS patients, which highlighted increased PDL1 staining in 4 of 5 AS patients. Though PDL1 expression can often indicate that a PD1 inhibitor may be effective, there had been no published instances in 2016 of AS patients being treated with an approved PD1 inhibitor such as pembrolizumab, which was initially approved for melanoma. When Dr. Fajgenbaum encountered a patient in 2016 with metastatic AS who was out of options, he requested  PDL1 staining, which confirmed increased expression and, in a pioneering approach, treated an AS patient with the PD1 inhibitor pembrolizumab. Remarkably, as of 2025, this patient has remained in remission for over 9 years, and many more patients have been treated successfully with this treatment. The promising outcomes have since led to multiple clinical trials investigating PD1 inhibitors for AS and the recommendation of PD1 inhibitors for AS in NCCN Guidelines marking a significant shift in the treatment paradigm for this aggressive cancer.