How Global Work Groups are Advancing Ectodermal Dysplasias Research

March 7, 2023March 7, 2023 Category: Research Posted by Mary Fete

For four days in October, 2021, 80 experts from around the world came together to chart a course for the future of ectodermal dysplasias research. The ultimate goal was “Translating Discovery to Therapy.” The International Ectodermal Dysplasias Research Conference in Charlotte, North Carolina was truly a landmark event in our 40-year history. NFED Board of Directors (BOD) and Scientific Advisory Council (SAC) members also participated in the Conference.

At the end of the conference, the group outlined next steps and deliverables. Several work groups were established to work in specialized areas. We plan on supporting multiple innovative research initiatives over the next several years!

We want to share this update with you now, but stay tuned for more exciting updates in the future.

Registry and Biobank Work Group

Work Group Members: Anil Vora (NFED BOD); Becky Abbott, MPH (NFED); Clayton Butcher, MD (NFED SAC); Christine Bodemer, MD, PhD (Necker Enfants Malades Hospital); Francesca Fusco, PhD (Institute of Genetics and Biophysics); Kayla Hollenkamp (NFED Work Group Assistant); Jacques Monnet, MBA (IP – France); Maranke Koster, PhD (NFED SAC); Mary Fete, MSN, RN, CCM (NFED); Matilde Valeria Ursini, PhD (Institute of Genetics and Biophysics); Tim Wright, DDS, MS (NFED SAC/BOD).

The NFED plans to launch a new patient registry and biobank, which will be a database of important genetic and health information for ectodermal dysplasia patients. Patient registries can be a powerful tool for any disease. The registry can track the course of disease, look at various treatment options and evaluate their effectiveness and outcomes. Registries can be helpful in looking at prognosis, disease outcomes and quality of life. Registries are also helpful in many other areas when looking at various syndromes and diseases.

An important aspect of the registry is the ability to survey different patient populations within the ectodermal dysplasias community to allow patients to indicate their areas of priority in regard to research and treatment. We believe it is crucial to incorporate the patient voice and recognize patient survey responses to inform our research priorities and guide us in determining areas of need.

The new registry will be hosted by Genetic Alliance. We are in the process of finalizing the details so please watch for updates!

Wound Healing Work Group

Work Group Members: Becky Abbott, MPH (NFED); Daniel Aberdam, PhD (INSERM); Brad Amendt, PhD (University of Iowa); Mary Fete, MSN, RN, CCM (NFED); Tim Fete, MD, MPH (NFED SAC); Encarna Guillen-Navarro, MD, PhD (Virgen de la Arrixaca University Hospital); Smail Hadj Rabia, PhD (INSERM); Kayla Hollenkamp (NFED Work Group Assistant); Maranke Koster, PhD (NFED SAC); Peter Marinkovich, MD (Stanford University); Sarah Millar, PhD (Icahn School of Medicine – Mt. Sinai); Maria Morasso, PhD (NIH); Shirley Parraga (East Carolina University); Elaine Siegfried, MD (NFED SAC); Stefano Sol, PhD (Harvard Medical School); Virginia Sybert, MD (Past NFED SAC); Tim Wright, DDS, MS (NFED SAC/BOD).

The Wound Healing Work Group is composed of an international group of scientists, clinicians, and patient advocates. The objective of the Work Group is to create a roadmap for developing new wound-healing therapies, specifically for individuals affected by ankyloblepharon-ectodermal defects-cleft lip and/or palate (AEC), ectrodactyly-ectodermal dysplasia-clefting (EEC), and Goltz syndromes.

The group’s discussions have centered on the current barriers to therapy development. These barriers include limited understanding of the nature of the wounds and their normal progression and a lack of access to patient educational materials and treatments. To begin to overcome these barriers, the Work Group has identified two short-term priorities.

1. Natural History Study of Wound Healing – Many patients affected by AEC, EEC, and Goltz syndrome experience large wounds or wounds that do not heal naturally. However, our knowledge on the behavior of these wounds is very limited. For example, we do not know how they normally heal, how long it takes for wounds to heal, if they recur in the same areas, and how often new wounds develop. It is important to better understand these characteristics, so that the effectiveness of therapeutic interventions can be properly evaluated.

To this end, the NFED will develop a protocol to study the natural history of wound healing. Drs. Maranke Koster and Peter Marinkovich are the project leads. We are currently evaluating mobile device apps that are designed to image and measure wounds at various stages. The apps are designed to be user-friendly, and can be used at home to image the wounds. The images will then be analyzed by our research team. The hope is that if we can better understand the history of these wounds, treatments can be implemented at various stages.

2. Wound Healing Workshop – The NFED is planning a work group meeting and workshop focused on wound healing at the end of 2023. The objectives are two-fold. First, we will bring experts together to discuss next steps and funding opportunities.

Second, we will invite individuals affected by wound healing challenges to participate in the workshop and to contribute skin biopsies and blood samples. These samples are desperately needed by researchers so they can develop treatments and cures for these devastating wounds. These samples will be used by researchers to gain a better understanding of the diseases, thereby facilitating the development of new and better therapies.

Funding research to find treatments for wound healing is a high priority for the NFED. Stay tuned!

Prevalence Work Group Update

Work Group Members: Becky Abbott, MPH (NFED); Brad Amendt, PhD (University of Iowa); Clayton Butcher, MD (NFED SAC); Maria Carmen-Martinez-Romero, PhD (Virgen de la Arrixaca University Hospital); Angus Clarke, DM, FRCP, FRCPCH (Cardiff University); Mary Fete, MSN, RN, CCM (NFED); Tim Fete, MD, MPH (NFED SAC); Francesca Fusco, PhD (Institute of Genetics and Biophysics); Kathy Grange, MD (NFED SAC); Encarna Guillen-Navarro, MD, PhD (Virgen de la Arrixaca University Hospital); Kayla Hollenkamp (NFED Work Group Assistant); Mark Kiel, MD, PhD (NFED SAC); Maranke Koster, PhD (NFED SAC); Richard Lewis, MD, MS (NFED SAC); Beau Meyer, DDS, MPH (NFED SAC); Jacques Monnet, MBA (IP – France); Karl Nelsen, PA-C (NFED BOD); Holm Schneider, MD, PhD (University Hospital Erlangen); Clark Stanford, DDS, PhD, MHA (NFED SAC); Matilde Valeria Ursini, PhD (Institute of Genetics and Biophysics); Anil Vora (NFED BOD); Kara Withrow, MS, CGC (GeneDx); Tim Wright, DDS, MS (NFED SAC/BOD); Matija Zelic, PhD (Sanofi Corp.).

The Prevalence Work Group is composed of professionals from North America and Europe with a special interest in basic science, genetics and/or clinical care of the ectodermal dysplasias. The Work Group has been meeting regularly since April 2022.

The key goal of the Work Group is to evaluate databases and partnerships to establish more accurate and valid prevalence estimates of the more common ectodermal dysplasias.

Initial discussions led to the following potential information sources:

1. State records: such as health surveys of children enrolled in public education.
2. Surveying physicians and dentists, assessing the population of ectodermal dysplasia patients for whom they provide care.
3. Insurance claims.
4. Electronic medical record searches.
5. Literature review for prevalence numbers already published.
6. Various health systems.
7. Kaiser Permanente and other groups that are both provider and payer, therefore perhaps more interested in learning more about the prevalence and spectrum of ectodermal dysplasias, to manage cost through better preventive management.

Prevalence Work Group member, Jacques Monnet, provided prevalence data published in Orphanet. Orphanet is a European initiative that aims to improve the management and treatment of rare diseases. It comprises a database dedicated to information on rare diseases and orphan drugs, and offers services adapted to the needs of patients and their families, health professionals, and researchers.

The primary areas of effort currently are:

1. Working with The University of Missouri School of Medicine Health Management and Informatics (HMI) Department to search either the large electronic medical record database of Cerner EMR or a large consortium of PCORI (Patient Centered Outcomes Research Institute) medical institutions across the Midwest and West.

This work came to a stall following the announcement of the retirement of the Department Chair of HMI, with whom we were working directly. We have now arranged to meet with the director of the University of Missouri/Cerner/Oracle consortium to try to move forward again.

2. Working with The Ohio State University School of Dentistry, Nationwide Children’s Hospital and PEDSnet (PEDSnet is a consortium of 11 of the USA’s premier pediatric hospitals/health care systems), all of which use EPIC electronic medical records.

PEDSnet is a pediatric learning health system dedicated to discovering and implementing new ways of providing the best care and improving health outcomes for children. They have a department of scholars and researchers dedicated to using a sophisticated approach to searching the millions of electronic medical records available to them for data collection. Preliminary meetings with PEDSnet have been very positive and it seems likely that this could be a rich source for defining prevalence rates of the most common ectodermal dysplasia syndromes.

The NFED is looking at other options as well to see if we can obtain good prevalence numbers for the syndromes.

Diagnostics Work Group Update

Work Group Members: Becky Abbott, MPH (NFED); Brad Amendt, PhD (University of Iowa); Clayton Butcher, MD (NFED SAC); Maria Carmen-Martinez-Romero, PhD (Virgen de la Arrixaca University Hospital); Angus Clarke, DM, FRCP, FRCPCH (Cardiff University); Mary Fete, MSN, RN, CCM (NFED); Tim Fete, MD, MPH (NFED SAC); Francesca Fusco, PhD (Institute of Genetics and Biophysics); Kathy Grange, MD (NFED SAC); Encarna Guillen-Navarro, MD, PhD (Virgen de la Arrixaca University Hospital); Kayla Hollenkamp (NFED Work Group Assistant); Mark Kiel, MD, PhD (NFED SAC); Maranke Koster, PhD (NFED SAC); Richard Lewis, MD, MS (NFED SAC); Beau Meyer, DDS, MPH (NFED SAC); Jacques Monnet, MBA (IP – France); Karl Nelsen, PA-C (NFED BOD); Holm Schneider, MD, PhD (University Hospital Erlangen); Clark Stanford, DDS, PhD, MHA (NFED SAC); Matilde Valeria Ursini, PhD (Institute of Genetics and Biophysics); Anil Vora (NFED BOD); Kara Withrow, MS, CGC (GeneDx); Tim Wright, DDS, MS (NFED SAC/BOD); Matija Zelic, PhD (Sanofi Corp.).

The Diagnostics Work Group is composed of individuals from Europe and North America, each of whom has a professional interest in the basic science, genetics and/or clinical care of individuals affected by ectodermal dysplasias. The group has been meeting regularly since April of 2022.

The key goal of the Work Group is to examine opportunities to establish the diagnosis of an ectodermal dysplasia during pregnancy or as early as possible after birth of an affected individual.

Explore methods to support the stated key goal:

1. Advocate to include as many ectodermal dysplasia genes as possible on prenatal screening panels.
2. Advocate for screening for fetal tooth germs on mid-term prenatal ultrasound studies, so that individuals likely to have hypodontia will be identified in time to enroll in potential in-utero treatment protocols.
3. Advocate for continued efforts to develop and disseminate non-invasive prenatal diagnosis (NIPD) capabilities for x-linked hypohidrotic ectodermal dysplasia (XLHED) and potentially other ectodermal dysplasias.

Work to pursue the above plans include:

1. Recruited Kara Withrow, MS, CGC, Senior Genetics Counselor from GeneDx to join the Work Group and serve as a resource regarding genomics. Ms. Withrow provided an extensive review of current prenatal screening panels available in the United States. She also provided information on a large-scale, postnatal screening study being conducted at Columbia University in collaboration with GeneDx and other parties.

The Diagnostic Work Group has established contact with the chief investigator of this study and is preparing background information to submit for addition of the more common ectodermal dysplasias to this study. The intent of the study is to identify individuals affected by rare disorders for which potential cures or treatments might be available currently or in the foreseeable future so that intervention can be initiated as early as possible in infants or young children.

2. The Diagnostics Work Group has had multiple interactions with the American Institute of Ultrasound in Medicine and has provided the AIUM with extensive documentation of the efficacy of assessing tooth germs in mid-trimester. The desire of the Work Group is to have the AIUM make a formal recommendation for assessing tooth germs in mid-trimester prenatal ultrasound studies. We are currently waiting on the response of the Clinical Standards Committee for Obstetrical Ultrasounds of the AIUM. In addition to the efforts with the AIUM, one of the workgroup members has agreed to contact the European counterpart of the AIUM with the same request.

3. Dr. Michelle Wood, collaborator with Dr. Angus Clarke in Wales, gave a detailed presentation on the science behind and the progress with the XLHED Non-Invasive Prenatal Diagnosis (NIPD) study in Wales. Unfortunately, their institution is unable to move forward with this study. The Diagnostic Work Group is currently working to identify other lab(s) which could take on this NIPD research with XLHED.

Conference Proceedings Published

In December 2022, the American Journal of Medical Genetics published a conference summary of our work during 2021’s International Ectodermal Dysplasias Research Conference. Read the article, “Rare Diseases of the Ectoderm: Translating Discovery to Therapy,” to learn more.