Funded Research – 2018

The HEDGE study represents the most comprehensive, collaborative effort to date in seeking to understand the underlying causes of hypermobile Ehlers-Danlos syndrome at the level of genes and gene expression. If we can achieve a better understanding of the underlying genetics and the gene expression abnormalities, we may be able to develop diagnostic tests and find more specific treatments for hypermobile EDS—and, potentially, the hypermobility spectrum disorders.

There have been great strides in biotechnology over the last two decades and the ability to understand and find treatments for genetic syndromes is at a turning point. Detailed research into the underlying issues causing hEDS and HSD will help determine where to target therapy. This genome sequencing study is the next step in our overall project to make the hope of these new technologies a reality.

The HEDGE study is the first and only population study in hypermobile Ehlers-Danlos syndrome to sequence 1000 people. Unlike studies of specific families, HEDGE is designed to provide information about causative genetic variants in the hEDS population by using statistical methods to identify variants that occur more commonly in hEDS. Studies in specific families have uncovered variants that appear to cause hEDS findings in a family, but no studies to date have yet shown findings that are thought to affect more than about 2% of people with hEDS. HEDGE is directed at understanding the remaining 98%.

Research Fund: $1,000,000
Primary Investigator:
The Hypermobility Biology Network

Research Updates: May 2022

People with hypermobility spectrum disorder (HSD) often have pain, coordination problems, and low tolerance to activity and exercise. Body awareness training, such as Feldenkrais, may help people manage these challenges. This pilot study will have a convenience sample of 10 individuals with symptomatic HSD participating in a 12-session Feldenkrais program to teach body and movement awareness.

Feldenkrais is a form of movement retraining aimed at improving efficiency and reducing muscle guarding and pain during movement.  It uses guided visualization techniques during small movements to help the individual explore using stabilizing muscles in a safe range of motion.  It is a type of mindful movement that has been used successfully for managing chronic pain.

The goal of this pilot study is to see whether participants in the Feldenkrais program report decreased pain, improved function, and improved self-efficacy (confidence in their ability to take care of themselves). If there are improvements in any of these outcomes, we hope to be able to determine whether these changes are related to improved self-awareness (interoception) or decreased fear of movement (kinesiophobia).

Another potential benefit from this research will be to establish a research design framework for clinicians interested in performing similar pilot studies using other body awareness therapy approaches such as Pilates, Tai Chi, etc. Clinician-led pilot studies such as these can lead to future, more definitive randomized control studies.

Research Fund: $5,000
Primary Investigator:
Leslie Russek, PT, DPT, Ph.D., OCS
Physical Therapy Department
Clarkson University
Potsdam, NY, 13699-5880

Multidisciplinary pain management is recommended as best practice to not only reduce pain but also to improve functional ability when providing care to children and adolescents with chronic pain.

As children with hypermobile Ehlers-Danlos syndrome (hEDS)/hypermobility spectrum disorder (HSD) have an increased risk of injury and prolonged recovery time post-injury, standard multidisciplinary pain programs may not be as effective for children with hEDS/HSD.

However, we currently don’t know if the chronic pain experience and associated symptoms of children with hEDS/HSD are similar to that of their non-hEDS/HSD peers. We also don’t know if the outcomes from multidisciplinary pain management are different for children with hEDS/HSD than that of their unaffected peers. A better understanding of these differences may assist us to develop tailored multidisciplinary chronic pain management programs for children with hEDS/HSD.

Children attending the main pediatric chronic pain clinics in Sydney, Australia, have been recruited into this study which is currently underway. We are measuring how many children attending have generalized HSD (G-HSD) or hEDS. Each child completes questionnaires about their pain, fatigue, mental health, and other symptoms at the initial presentation and again six months later, including their global impression of change and satisfaction with multidisciplinary pain management services. However, children with G-HSD reported significantly lower functional abilities than their non-hypermobile peers.

The results of this study will provide critical data to assess the potential need for future studies assessing the efficacy of a hypermobility-specific intervention designed to reduce the pain of children and adolescents with G-HSD/hEDS and allow for immediate translation of findings into current clinical practice.

$5,000
Primary Investigator:
Verity Pacey B App Sci (Phty), PhD
Senior Lecturer
Department of Health Professions | Faculty of Medicine and Health Sciences
G815, 75 Talavera Rd
Macquarie University, NSW 2109, Australia​

Several types of EDS have been identified and may affect structures in the mouth including early onset​ ​inflammation of the tissues around the teeth, abnormally shaped roots, and functional problems in muscles​ ​and the temporomandibular joint, which impede diagnosis and treatment.

Sleep-disordered breathing (SBD) has recently been reported in EDS and is often associated with specific characteristics of the​ ​craniofacial profile.

The aim of this Danish study is to examine the teeth, chewing function, th​e ​craniofacial profile, and upper respiratory tract of patients with EDS compared to healthy age and gender-matched control group. The hypothesis of the study is that there will be differences in teeth, function,​ ​craniofacial profile, and upper respiratory tract between patients with EDS and a healthy control group.

The​ ​results will contribute to a better understanding of the characteristics of EDS and thus improve diagnostics and treatment of EDS. In addition, this new knowledge is relevant for dentists as many dentists meet​ ​patients with EDS in their daily clinic.

$5,000
Primary Investigator:
Liselotte Sonnesen
Leder af specialtandlægeuddannelsen i Ortodonti
Specialtandlæge i Ortodonti, ph.d., dr.odont
Det Sundhedsvidenskabelige Fakultet

Fagområde Ortodonti
Københavns Universitet
Nørre Allé 20
2200 København NDIR 35326670

In the past 15 years, scientific advances have led to acceptance amongst medical professionals that​ ​bowel symptoms are very common in hypermobility-related disorders, in particular, the hypermobile​ ​Ehlers-Danlos (hEDS) subgroup. This group of patients has a problem with the extracellular matrix​ ​(ECM) which is the scaffold that keeps joints and organs intact. Patients with hEDS experience symptoms similar to those who have Irritable Bowel Syndrome thereby​ ​constituting a strong link​ ​between the two types of conditions.

If we can find the basis for this link, we can design or optimize​ ​medications to manage the bowel symptoms that address the main abnormality in the tissues that causes these disorders. Thus it will be easier to intervene with patients susceptible to abdominal (tummy) pain​ ​constipation and/or rectal prolapse using existing or novel treatments. Finally, it will make a major​ ​difference for patients to know what is the root of their problem, which is not currently the case in the​ ​majority of patients with functional gut disorders (where the cause is not known).

Previously we have characterized a type of ECM tissue called Tenascin X (TNX) in the mouse and​ ​human gut and found that it is important for gut function. We now want to understand why abdominal pain​ ​is common in patients with hEDS and in TNX deficiency. If a clearer picture of why pain is common in​ ​patients with connective tissue disorders is found, it would pave the way for better diagnosis and​ ​treatment. We have obtained a TNX knockout mouse (where the TNX gene has been removed), developed purpose-designed techniques, and investigated TNX’s role in several gut functions.

In​ ​particular, we have studied how TNX influences the function of nerves that control sensation and​ ​movement of the gut. For this research grant, we would like to use the TNX-KO mouse model to explore the reason​ ​for increased pain in TNX deficient and hEDS patients. We have obtained stomach and gut biopsies​ ​from patients diagnosed with hEDS, which we will study to see how different pain nerves look​ ​compared to biopsies from normal people.

$5,000
Primary Investigator:
Dr. Rubina Aktar
Queen Mary University of London​