Ehlers-Danlos Syndrome Research

Deciphering the Genetic and Molecular Foundations of EDS

The Ehlers-Danlos Syndromes

Ehlers-Danlos syndrome (EDS) is a group of genetic connective tissue disorders characterized by joint hypermobility, skin hyper-extensibility, and tissue fragility. There is phenotypic and genetic variation among the 14 subtypes. Professor Rodney Graham, a lead EDS expert, once said "No other condition in the history of modern medicine has been neglected in such a way as Ehlers-Danlos Syndrome."

The Norris lab is ready to change that.

Hypermobile Ehlers-Danlos Syndrome

The most common disease you've never heard of

Hypermobile EDS (hEDS) is the most common type of EDS, estimated to affect around 1 in 500 individuals, with varying degrees of severity and presentation. Despite its prevalence, hEDS has remained a neglected condition in the medical and scientific fields. To date, there are no treatments or cures for hEDS beyond symptom management.

Living with hEDS can be challenging, as it often involves a range of symptoms that vary from person to person. These can include:

Joint Hypermobility: Increased flexibility and range of motion in the joints, which can lead to joint instability and pain.
Chronic Pain: Persistent and often severe musculoskeletal pain that can affect daily life.
Skin Hyperextensibility: Skin that is more elastic and prone to easy bruising and scarring.
Fatigue: Overwhelming fatigue that is not relieved by rest.
Gastrointestinal Issues: Digestive problems, such as gastroparesis, irritable bowel syndrome (IBS) or gastroesophageal reflux disease (GERD).
Cardiovascular Symptoms: Mitrovalve prolapse, vascular compression syndromes, and blood pressure issues.
Comorbid Conditions: hEDS frequently occurs with conditions such as dysautonomia/POTS and mast cell activation disorder (MCAD).

Hypermobility Spectrum Disorder (HSD) is a related connective tissue disorder characterized by joint hypermobility, musculoskeletal symptoms, and connective tissue issues. HSD is diagnosed based on clinical evaluation and similarly to EDS, has a range of possible joint and systemic manifestations. Further research is needed to better understand HSD.

Current EDS Initiatives

EDS/HSD Survey

EDS and HSD are related to a wide array of comorbid conditions, but comprehensive clinical overviews of these conditions are lacking in scientific literature. We are gathering a large data set of the multisystemic problems related to EDS and HSD to inform the direction of future research studies of EDS and HSD at the Norris Lab and beyond.

hEDS Genetic Registry

The Norris lab seeks to advance the understanding of hEDS through cutting-edge research into the genetic factors that underlie this complex condition. Through our comprehensive genetic registry and collaborative research efforts, we hope to improve diagnosis and treatment for individuals living with hEDS.

Ehlers-Danlos Mouse Models

Using state of the art CRISPR-Cas9 mediated genome editing, the Norris lab is working to develop mouse models of every subtype of Ehlers-Danlos. To advance the research into these diseases, we plan to make these mouse models available to other research institutions at no charge.

Patient-Scientist Initiative

The Norris lab belives that patients are the experts in their own diseases and has pioneered the "patient scientist" model of research. We offer multiple opportunities for students with hEDS who have an interest in research or medicine to gain experience in the lab.

Areas of Research

Family Genetics

We are using whole exome sequencing (WES) to understand genetic changes that contribute to hEDS within families that have enrolled in our hEDS registry. By studying the genetic makeup of affected individuals as well as their unaffected relatives, we aim to identify key genetic changes and pathways that can improve diagnosis and treatment.

Population Genetics

To understand common genetic variants associated with hEDS, we are working on genome wide association studies (GWAS) using genetic samples from our hEDS registry. Through GWAS, we aim to identify specific genetic markers that play a role in hEDS, and specific variants that play a role in different EDS phenotypes and comorbidities. Similar to our family genetic studies, this data with help to improve our understanding of the disease, with the goal of developing better diagnostic tools and therapies.

Mast Cells

Frequently observed with EDS is Mast Cell Activation Syndrome (MCAS), characterized by heightened mast cell activity and degranulation, resulting in a range of allergic symptoms. We are working to understand the intricate connection between connective tissue dysfunction and mast cell activation. Our aim is to enhance the management of both MCAS and EDS, offering a more comprehensive approach to improving the lives of affected by these conditions.

Connective Tissue Biology

hEDS patients are known to have weak connective tissue, leading to joint hypermobility and instability. To understand the altered connective tissue present in hEDS patients, we are using a variety of biological models including in vitro and in vivo systems. We are analyzing the expression of key proteins involved in connective tissue formation and maintenance, such as collagen, elastin, and enzymes involved in post-translational modifications to look for differences in protein expression patterns. Insights from these studies will guide further research into the biological mechanisms behind hEDS.

Biomarker Discovery

There is a clinical need for the development of diagnostic tools for hEDS and HSD. Using plasma and serum samples from hEDS and HSD patients, we are using proteomic approaches to identify potential biomarkers that can be used to develop an accurate and sensitive diagnostic test. This would improve diagnostic capabilities and allow for earlier and accurate diagnosis in people with hEDS and HSD.

Dermatological Pathologies

Rare Types of EDS

While hEDS is not considered a rare disease, the other subtypes of EDS are exceeding rare, with some subtypes only reported in a few families worldwide. Research on these conditions is lacking, even in cases where the genetic cause is known. We are interested in studying the underlying biology of rare subtypes of EDS, and have developed a mouse model repository to do so.

Gastrointestinal Manifestations

The scientific literature on gastrointestinal manifestations has previously established symptoms associated with hEDS such as abdominal pain, nausea, and constipation, with little literature assessing functional GI disorders in hEDS. Therefore, we are conducting a medical chart review of patients with hEDS, to investigate the type and prevalence of gastrointestinal pathologies, diagnostic testing approaches, interventions and treatment approaches, and the presence of additional comorbidities.

Vagus Nerve Stimulation

The vagus nerve is one of the longest nerves in the body, extending from the brainstem down to the abdomen, and it plays a key role in regulating various involuntary bodily functions. In collaboration with Dr. Steven Kautz, Dr. Bashar Badran, and Dr. Heather Boger, we are currently conducting a clinical trial centered on Vagus Nerve Stimulation (VNS). Our study will use both mouse models of hEDS and patient participants to investigate the efficacy of VNS as a treatment for symptoms and comorbidities associated with EDS.

Musculoskeletal Biorepository

In collaboration with Dr. Josef Eichinger, we are creating a biorepository of 10,000 patient samples from synovial fluid joints for current and future research. The study aims to generate a bank of these synovial fluid tissue samples, detect biomarkers of early disease stages of various conditions (including orthopedic manifestations of EDS), and eventually develop therapeutics to reduce the need for orthopedic surgical interventions.

Tethered Cord Syndrome

Tethered cord syndrome is a comorbid condition observed in some patients with EDS. The symptoms can include lower back pain, balance problems, lower extremity weakness, sensory loss, and bowel and/or bladder incontinence, which all overlap with other neurological disorders causing diagnostic challenges. In collaboration with Dr. Sunil Patel, we will be studying filum terminale tissue collected during surgical interventions, with the goal of understanding the biological mechanism of tethered cord syndrome. We will also be studying blood and cerebrospinal fluid samples to identify biomarkers of early disease.