Erdheim-Chester Disease Global Alliance

The ECD Global Alliance is dedicated to enhancing all research and knowledge of Erdheim-Chester disease through supporting leading medical research. The ECD Global Alliance funds research dedicated to exploring the diagnosis, cause, treatments, and cure of Erdheim-Chester Disease.

In addition, the organization works with research teams and patients around the world to facilitate communication between the two groups.

2022 Grant Period Open: Currently Requesting Letters of Intent

The ECD Global Alliance is soliciting Letters of Intent for funding research projects focused on the study of Erdheim-Chester Disease. Two (2) one-time grants will be awarded to two qualified investigators conducting original research with goals that translate to the patient-centered needs of earlier detection, better treatment with fewer adverse effects, and/or better symptom management.

Maximum Amount to be Awarded: Up to 200,000 USD per project

Duration of Grant: 2 Years

LOI Deadline: October 17, 2022

International proposals are welcomed.

The purpose of the ECD Global Alliance is to help those affected by Erdheim-Chester Disease. As such, the Alliance’s mission is to provide support, promote research, raise awareness, and share educational material related to ECD.

Erdheim-Chester Disease is a rare non-Langerhans cell histiocytic neoplasm. The disorder is characterized by excessive production and accumulation of histiocytes that infiltrate the loose connective tissue of the body. Unless successful treatment is found, organ failure can result. Erdheim-Chester Disease usually affects adults, although childhood cases have been documented. It can affect both men and women. Disease involvement may include long bones of the legs and arms, skin, tissues behind the eyes, lungs, brain, pituitary gland, kidney, abdominal cavity, heart, adrenal glands, and more rarely other organs.

The ECD Global Alliance is interested in receiving LOIs for any study that can lead to an increase in knowledge related to the pathophysiology, diagnostics, treatments, and symptom/side effect mitigation of Erdheim-Chester Disease and other histiocytic disorders. All studies, whether basic science, clinical or epidemiological will be considered.

Funded projects should be patient-centered, with research questions and outcome measures that are relevant to patients. The submitted study proposal must include collaboration plans among investigators from different institutions, with international collaborations encouraged.

To apply, contact us.

Recent Grant News

Dr. Francesco Pegoraro

The ECD Global Alliance has awarded the 2021 ECD Research Grant to Dr. Francesco Pegoraro, with Meyer University Children’s Hospital, Florence, Italy. The winning proposal, Exploring the genetic landscape of Erdheim-Chester disease by integrating GWAS and -omic data, was selected for funding for $50,000. The ECDGA is honored to be funding this groundbreaking work and believes it will result in a brighter future for ECD patients and a better understanding of histiocytosis. View Press Release

Dr. Gaurav Goyal

Dr. Gaurav Goyal is an Assistant Professor of Hematology-Oncology and ECD Care Center lead physician at the University of Alabama Birmingham. In collaboration with Uplifting Athletes, Dr. Goyal has been awarded a $20,000 grant for a Histiocytic Disorders Survivor Study (HDSS). Results from the study will be used to help devise guidelines for the follow-up care of ECD and other histio patients and develop intervention strategies in the future to mitigate long-term complications. The study aims to utilize the ECDGA Patient Registry to understand the spectrum of long-term health conditions that patients with ECD struggle with, including quality of life and chronic pain. View Press Release

Please check back soon for the 2022 open enrollment period. We are looking for new ideas and researchers to further the understanding of ECD and its treatment.

Grant Applications and Review Process

A call for Letters of Intent (LOI) is sent out to all known avenues for dissemination and is posted on the ECD Global Alliance website. Submitted LOIs are reviewed by a committee of qualified researchers and clinicians.  The investigators submitting projects that hold the most promise for making a significant and lasting advance in the knowledge and treatment of ECD are then invited to submit a complete proposal.

A Grant Application Review (GAR) Committee made up of qualified researchers is assembled to review submitted application proposals. Individuals on the committee first review each application independently. The GAR Committee then comes together as a group to share comments and discuss each application submitted. This committee provides the ECD Global Alliance Board of Directors with a ranking order of the applications. The Board of Directors then makes the final funding decision and notifies the applicants. Letters of Intent are submitted via an LOI submission form and are reviewed per an LOI Review Process and criteria. Invited proposals are then submitted and reviewed according to the ECDGA  Grant Application Process.

Previous Grants Awarded

In April 2010, only one month after receiving a 501(c)(3) designation, the ECD Global Alliance (ECDGA) announced it would be awarding a $50,000 ECD research grant and requested proposals to the international medical research community.  In November 2010, the first grant recipient was chosen. The organization has awarded seven $50,000 research grants to study Erdheim-Chester Disease, as well as a $316,000 grant to establish an ECD Patient Registry.

2019 ECDGA Grant Awarded to Nicole Coufal, MD, PhD

In 2019, a $50,000 young investigator award was granted to Nicole Coufal with the University of California, San Diego. Study Title: “Pathophysiology of Neurodegenerative Erdheim-Chester Disease and Langerhans Cell Histiocytosis” The long-term goal of this project is to not only improve the understanding of ECD and LCH-associated neurodegeneration but to generate hypotheses and models that will allow for novel drug screening paradigms to ultimately improve the treatment of the devastating neurological form of this disease.

2017 ECDGA Grant Awarded to Benjamin H. Durham, MD

Memorial Sloan-Kettering Cancer Center in New York received a 2017 research grant in the amount of $50,000.  Principal investigator, Benjamin H. Durham, MD, leads the study Defining the Cell-of-Origin of Erdheim-Chester Disease.  The bone marrow cells from ECD patients will be studied to try to determine the cells that cause ECD.  With this information, it may be possible to create a successful model of ECD that can be used for future studies by scientists from around the world.  A secondary goal of this study will be to compare the gene profile of ECD cells with the cells of other blood cancers that are often seen in ECD patients. Dr. Durham is a hematopathologist and molecular genetic pathologist who has previously identified various genetic mutations associated with ECD.  These findings have led to immediate therapeutic options for patients.

Interim Report Read more…

Through comprehensive genomic sequencing analyses of the largest group of children and adults (266 patients) sequenced to date with histiocytic neoplasms of which the largest subgroup is Erdheim-Chester disease (ECD), several new and targetable kinase genetic alterations have now been discovered in ECD and other histiocytoses. The discovery of BRAFV600E mutations in these diseases around 8 years ago resulted in our understanding of these disorders as a type of cancer with future studies leading to the FDA-approval of vemurafenib for adult patients with BRAFV600E-mutated ECD (Hyman, D et al. NEJM 2015). However, it is still not clear what cell types lead to the development of ECD and other histiocytoses (Mass E, et al. Nature 2017) nor are all the genetic alterations in this disease defined. Here we identify the first examples of recurrent CSF1R kinase mutations in any disease, as well as numerous additional new kinase alterations driving ECD and other histiocytoses.

The discovery of CSF1R mutations is significant because (1) CSF1R defines the monocyte/macrophage lineage and, therefore, reveals histiocytic neoplasms as derived from monocytes/macrophages, and (2) there are numerous inhibitors of CSF1R in development (and one is already FDA-approved for other diseases). We also demonstrate the first example of clinical responses to ALK inhibition in ALK-rearranged histiocytosis as well as evidence of preclinical responses to CSF1R inhibition in CSF1R-mutant cells. These data are highly clinically important and will be of immediate interest due to the excitement about CSF1R inhibition in cancer, RET inhibition, and precision medicine for rare disorders such as ECD.

2015 ECDGA Grants Awarded

(Janku, et al) Filip Janku, MD, Ph.D., and Abdel-Wahab, MD were awarded a $50,000 grant for their project, “Understanding and targeting novel molecular alterations in Erdheim-Chester Disease without the BRAFV600E mutation.” The purpose of this study is to discover treatable mutations found in BRAF-negative ECD patients and test in the lab which treatments will most likely work best for these patients. Final Report Read more…

As part of an international collaboration between Drs. Janku, Abdel-Wahab, and collaborators in France, the first comprehensive genomic analysis of ECD including both whole-exome sequencing (WES) paired with whole transcriptome analysis (by RNA-seq) was performed. This effort identified a number of recurring activating mutations and fusions in ECD and has since been published/
In addition, WES, RNA-seq, and targeted genomic analysis of ECD and related histiocytoses in the investigators’ clinical practices continue to be performed. To date, we have performed WES in ~40 ECD patients and have identified additional targeted genetic alterations not identified in the above publication.
Furthermore, targeted next-generation sequencing (NGS) or PCR of archival tissue samples and/or blood-derived cell-free (cf) DNA samples from 25 patients treated at MD Anderson and UCSD Moores Cancer Center were performed. Initial data were presented at the Annual ECD International Medical Symposium in September 2016. Since then the data set has been expanded to include samples from 9 patients treated at the Memorial Sloan Kettering Cancer Center (Dr. Eli Diamond) and 2 additional patients from MD Anderson.

Eli L. Diamond, MD, and Vaios Hatzoglou, MD were awarded a $43,000 grant for their project, “A Clinical, Structural, and Functional Neuroimaging Study of Cognition in Erdheim-Chester Disease.” The purpose of this study is to understand the neurological/cognitive effects of ECD. Interim Report Read more…

Researchers at Memorial Sloan Kettering Cancer Center are conducting a study about brain structure and brain function in ECD patients, funded by the ECD Global Alliance. What has prompted this study is the observation that ECD patients have difficulties with thinking and memory, often impairing normal work and function, as well as early data that ECD may change the brain’s structure and volume even without ECD tumors. Participants will undergo an MRI scan of the brain with special additional components, as well as thinking and memory testing. Potential participants are welcome to contact the study lead, Dr. Eli Diamond, at diamone1@mskcc.org.

Marina Ferrarini, MD, and Lorenzo Dagna, MD were awarded $50,000 for their project, “Tailoring Treatment for Erdheim-Chester Disease.” The Ferrarini and Dagna study focuses on understanding how malignant cells in ECD patients accumulate and interact with neighboring normal cells to fuel the disease, causing lesions and tumors to form. With this understanding, the discovery of a treatment strategy that can interrupt the processes, stopping the disease from progressing, may be possible. Final Report Read more…

Our study focuses on a better understanding of the pathogenic events operating inside ECD lesions, as well as the mechanisms exerted by selected drugs/new molecules on mutated histiocytes. This is expected to result in the discovery of novel strategies providing ECD patients with treatments that are more effective and with fewer side effects than those currently available. So far we have identified molecules and pathways that may have a key role in disease progression; we plan to investigate how these molecules act to fuel the disease and also to test the efficacy of potentially available inhibitors. In order to validate these findings and improve treatment for ECD patients, we are also taking advantage of state-of-the-art bioreactor technology. The bioreactor, originally developed by NASA spatial research, works under conditions of simulated microgravity, allowing the tissue to remain viable during culture and offering the unprecedented possibility to test and compare the effectiveness of treatments. We were able to apply this technology, which we have already exploited for other diseases, also to ECD tissues. We have collected information on the mechanisms exerted by available drugs, particularly kinase inhibitors, on ECD lesions, unveiling new putative therapeutic targets, in particular metabolic pathways, that can be further exploited to design new combination therapies. Finally, we have identified Chromogranin A, a pro-hormone associated with inflammation and heart failure, as a possible marker of cardiac disease also in ECD. This molecule can be detected in plasma samples and can be potentially used as a novel non-invasive procedure to monitor cardiovascular involvement and response to treatment in ECD patients.

2014 ECDGA Grant Awarded to Eli Diamond, MD

The 2014 grant was awarded to principal investigators Eli Diamond, MD from Memorial Sloan-Kettering Cancer Center in New York, and Matthew Collin from Newcastle University in the UK, for the “Design and Creation of a Global Registry Database for Erdheim-Chester Disease.”  The patient registry will be a collection of standardized information about the ECD group of patients to evaluate specified outcomes defined by this particular disease.  The data will serve a scientific, clinical purpose.  This is expected to be a two (2) year effort with a budget of $316,000 being granted from the ECD Global Alliance.

2013 ECDGA Grant Awarded to Omar Abdel-Wahab, MD

In September 2013, the ECD Global Alliance announced a $50,000 grant, awarded to Omar Abdel-Wahab, MD, David Hyman, MD, and Eli Diamond, MD from Memorial Sloan-Kettering Cancer Center in New York (MSK), New York for the study described as, “Somatic Genetic Alterations in the Pathogenesis and Therapy of Histiocytic Disorders.”  As described in the MSK press release, the aim of this study is to:

1.  Identify recurrent somatic genetic events in addition to BRAFV600E mutations in patients with ECD.

2.  Identify the cell of origin in ECD.

3.  Identify the optimal targeted therapy in histiocytic disorder patients with mutations activating kinase signaling.

Final Report Read more…

The phase II study of Vemurafenib in ECD and LCH patients bearing the BRAFV600E mutation was completed. This study was carried out in the context of an international study sponsored by Roche and the results were submitted to the New England Journal of Medicine with Dr. Hyman as the lead author. The results of this study will result in FDA approval of vemurafenib for ECD and LCH patients with the BRAFV600E mutation in the U.S.
In addition, a phase II clinical trial of the MEK inhibitor cobimetinib for ECD patients without the BRAFV600E mutation was opened. This trial is sponsored by Genentech and is open for patient enrollment as of Spring 2015.

As a corollary to the vemurafenib clinical trial, a collaborative study was performed with Dr. Filip Janku at MD Anderson Cancer Center to understand the utility of cell-free

DNA analysis to identify and track the BRAFV600E mutation in ECD patients. This work revealed that plasma and urinary cell-free DNA-based detection of the BRAFV600E mutation are more sensitive than conventional tissue-based BRAFV600E mutation testing.
These findings were recently published in Cancer Discovery and featured as the cover article.

As a collaborative effort with Drs. Julien Haroche and Jean-Francois Emile the largest genomic study of ECD patients to date was completed, which identified the true frequency of the BRAFV600E mutation in ECD as well as several, additional, novel therapeutically targetable mutations in ECD patients (including NRAS, KRAS, and PIK3CA mutations). This work was published in Blood and featured on the cover of Blood and in an “Inside Blood” Editorial.

2012 ECDGA Grant Awarded to Julien Haroche, MD, PhD

In April 2012, the organization announced a grant awarded to Laurent Arnaud, MD, Ph.D. and Julien Haroche, MD, Ph.D. from Hôpital Pitié-Salpêtrière in Paris, France for the study described as, “Understanding dendritic cell lineages in Erdheim-Chester disease: towards a non-invasive diagnosis.”  The aim of this study was to understand the primary mechanisms involved in the pathogenic differentiation of histiocytes in ECD, as well as to use these data to derive a screening & diagnostic test for ECD that would rely on blood sampling without the need for a biopsy.

Final Report Read more…

Twenty-seven patients diagnosed with ECD were evaluated.  The group was composed of WT and V600E genotypes and of treated and untreated patients.  Six different treatments were used across those patients who were treated.  Results showed notable differences among the WT and BRAF V600E patients not treated and treated.

2011 ECDGA Grant Awarded to Lorenzo Dagna, MD

The ECD Global Alliance 2010 grant was awarded to Lorenzo Dagna, MD at San Raffaele Scientific Institute in Milano, Italy for the study described as, “Hypoxia and inflammation in Erdheim-Chester disease microenvironment: insights on the pathogenesis and implications for therapy proposal.“  The aim of this study was to better define the microenvironment inside ECD lesions and to evaluate the possibility of using specific drugs, already available for human usage, as a means to find new therapeutic options for the disease.  The study ran from January 2011 until June 2012.  The results of this study can be found in the Journal of Clinical Oncology, Vol. 310, 2012, in an article entitled, “Tumor Necrosis Factor as a Master Regulator of Inflammation in Erdheim-Chester Disease: Rationale for the Treatment of Patients with Infliximab.”

Last updated: October 12, 2022