Research funded in 2019 by The Ehlers-Danlos Society

In 2019, The Ehlers-Danlos Society funded the following studies:

To view further research funded by The Ehlers-Danlos Society, please click here.

The Ehlers-Danlos Society aspires to offer grants annually, with calls for clinical research proposals early in the year and for basic science later in the year. We will also offer grants of varying value to reflect the different nature of researcher requirements, including microgrants.

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Hypermobile Ehlers-Danlos syndrome/Hypermobility spectrum disorders (hEDS/HSD) are characterized by generalized joint hypermobility, musculoskeletal pain, and minor systemic manifestations without a known molecular basis. Hence, its recognition remains an exclusion diagnosis based on a new set of clinical criteria.

From a point of scientific view, detailed knowledge of the pathogenetic mechanisms is an essential starting point for the development of targeted management/therapies for highly disabling signs that considerably reduce the quality of life and working ability of hEDS/HSD patients. Therefore, unraveling the complexities underlying the etiology of hEDS/HSD and their pathogenetic link with musculoskeletal pain will surely help in having a more feasible diagnostic assessment and/or prognostication of the disorder, and improving the knowledge in mechanisms of musculoskeletal pain generation and chronicization.

Musculoskeletal pain is a great burden for the general population in most developed countries. The proposed research may have a translational relevance and impact on the National Health Systems, considering the huge number of hEDS/HSD patients (several hundred patients with hEDS/HSD clinically evaluated in our Center) and thus reaching a definite diagnosis will stop the expensive and lengthy diagnostic process for these individuals.

Furthermore, the disclosure of the pathogenetic background of these patients will lead to the development of targeted management/therapies that will decrease the prescription of ineffective drugs and unnecessary evaluation, ameliorating patients’ management and treatment of the disease, likely contributing to the improvement of their healthcare.

In this scenario, the findings that will derive from the present research activity could address towards future research for the identification of serum diagnostic biomarkers, which might be a promising approach for non-invasive diagnostic tests for hEDS/HSD patients.

Research Fund: $50,000
Primary Investigator:
Marina Colombi, PhD
Full Professor of Medical Genetics
Department of Molecular and Translational Medicine Institution
University of Brescia
Viale Europa, 11 – 25123
Brescia, Italy

Read update: Read the report. 

We know that the lifespan for individuals with vEDS is shortened compared to unaffected family members but we are uncertain if the timing and nature of surgical and medical intervention for some of the catastrophic complications improve outcomes and, if not, what would be a better form of treatment or surveillance.

Our own records of some 1250 individuals with vEDS often provide only rudimentary details of the complications. We plan to obtain the medical records from this group and others through the ED Society registry and the vEDS Collaborative study from about 1000 individuals with vEDS documented by genetic testing.

We want to discover if medical intervention can be substituted for surgery, or if endovascular vascular treatment can be substituted for open surgical treatment, and we want to know if there are details of the surgery and post-operative care that can be changed to facilitate long-term survival.

To do this study we will obtain detailed medical records from about 1000 individuals with COL3A1 mutations and review their history and interventions. We will then determine if medical treatment can suffice in some situations and whether stenting is better than open surgery. We will also determine if fluid overload, a common event after surgery, is a great hazard in this group.

Research Fund: $75,000
Primary Investigators:
Sherene Shalhub, MD, PhD, and Peter Byers, MD
University of Washington
1959 NE Pacific Street
Box 35641
Seattle, WA 98195

Chronic pain is a major complaint in EDS patients. It is, to a variable extent, observed in all EDS subtypes, and a frequent reason for seeking medical help. It has a severe impact on daily activities, quality of life, and psychosocial functioning. Severe chronic pain can even shorten life expectancy. Nonetheless, currently used pain therapies do not result in adequate pain relief, and are associated with serious health risks. Chronic EDS pain thus represents an unmet medical.

Despite it being a huge clinical problem, it is at present unclear how pain starts and evolves over time in the different EDS subtypes. Most EDS subtypes are caused by defects in the biosynthesis of connective tissue, the tissue that supports and protects the body. Connective tissue is found in between other tissues everywhere in the body, including the nervous system. We hypothesize that aberrations of the connective tissues, caused by the genetic defects underlying EDS, lead to structural and/or functional changes in the peripheral and central nervous system and that these changes generate and maintain EDS-associated pain.

In order to explore this hypothesis, we will:
(1) assess and characterize pain and explore pain mechanisms in a cohort of cEDS and hEDS
patients, using validated questionnaires and experimental pain testing.
(2) assess pain-related behaviors in a validated mouse model for cEDS. Animal models provide the advantage of allowing in-depth studies of affected tissues, e.g. nervous tissue. We will document whether the pain is accompanied by anatomical, molecular, and cellular changes over time in the peripheral and central nervous tissues using state-of-the-art imaging and sequencing techniques.

We anticipate that our study will provide unprecedented insights into EDS-associated pain and associated changes in the nervous system. Our ultimate goal is to identify potential therapeutic targets for the development of better pain therapies for all EDS subtypes.

Research Fund: $75,000
Primary Investigator:
Fransiska Malfait MD, PhD
Senior Clinical Investigator, Head of Clinic Department
Center for Medical Genetics Institution: Ghent University
Corneel Heymanslaan 10
9000 Ghent

Ehlers-Danlos Syndrome (EDS) is a heterogeneous group of inherited disorders characterized by well-recognised signs and symptoms in various organs and tissues of the body. The mutations that cause EDS, especially vascular EDS, are many and varied in their nature. They also occur in several genes that encode both enzymes and structural proteins.

The best way to make sense of these disease-causing mutations is to collect them systematically and put linked accounts of the mutations and patient symptoms into a database. This allows researchers and clinicians to spot trends and improve decision-making in health care.

The Ehlers-Danlos Syndrome Variant Database provides comprehensive access to sequence variant data relating to the genetic basis of the various types of Ehlers-Danlos syndrome. There is excellent evidence that the database is widely used by both researchers and clinicians.

Mutation data have been collected for more than thirty years and are currently hosted in a purpose-built database that allows easy and free access to the data. Until about two years ago the maintenance of the data in the database, including the addition of new data, was a manageable task that could be accomplished without help or financial support. However, the rate of accumulation of new mutation data, brought about by the development of new diagnostic tests, has resulted in the need for financial support to ensure that the database can be maintained to the same high standard that was previously achievable.

The database software that is currently used is outdated and unsupported and proper funding of this endeavor would allow the database software and the disease-causing variant data content to be brought up to date.

A comprehensive program of updates and improvements to the database is proposed, including a change to where the database will be hosted. These measures will ensure an improved user experience and also safeguard the long-term viability of the database. This would bring about much-needed improvements to what the database offers the EDS community: researchers, medical staff, and the patients themselves.

Research Fund: $75,000
Primary Investigator:
Raymond Dalgleish PhD
Professor of Human Genetics
Department of Genetics & Genome Biology Institution
University of Leicester
Leicester, LE1 7RH

Hypermobility Ehlers-Danlos syndrome (hEDS) is the most common of the 13 EDS types. It is also the only type without identified causative genes. This study supports the analysis of gene expression (RNAseq) in people with hEDS compared with normal controls.

The goal is to identify genes that are differentially expressed in hEDS, thus pointing to relevant pathogenic processes and supporting candidate genes found in whole genome sequencing.

Research Fund: $69,020
Primary Investigator:
Christina M. Laukaitis, MD, PhD, FACP, FACMG
Director, Genetic Consultation and Counseling Services, UAHS Center for Applied Genetics and Genomic Medicine

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