An MUSC research team has received the 2023 Blue Sky Award to further the understanding and treatment of an often mischaracterized and dismissed disease, hypermobile Ehlers-Danlos syndrome (hEDS), using vagus nerve stimulation (VNS).
The team is led by stroke rehabilitation researcher Steven Kautz, Ph.D., chair of the Department of Health Sciences and Research in the College of Health Professions, and Russell "Chip" Norris, Ph.D., professor in the Department of Regenerative Medicine and Cell Biology in the College of Medicine. Other team members include Heather Boger, Ph.D., professor in the Department of Neuroscience, and Bashar Badran, Ph.D., professor in the Department of Psychiatry and Behavioral Sciences.
The Blue Sky Award is granted to an interdisciplinary team to assess the utility and value of a creative, daring idea that is unlikely to receive traditional funding due to its high-risk, high-reward nature.
This type of intrepid research can bring clinical breakthroughs. A breakthrough is urgently needed for hEDS, which is not well-understood but is devastating for many.
Members of the MUSC research team know this devastation firsthand.
"I have two children, both of whom have Ehlers-Danlos syndrome," said Kautz. He detailed that his children, both in their 20s, have been significantly affected by EDS. "My daughter is bedridden and has had her life completely disrupted from the time she became a teenager."
Likewise, the Norris lab has a personal investment in improving the lives of those with hEDS. It was Cortney Gensemer, Ph.D., an hEDS patient herself, who joined the Norris lab as a graduate student and led the team to study the disease.
"As a patient-scientist, I have a unique perspective in the lab," said Gensemer. "Combining my scientific background, personal experience and connection to the patient community allows me to contribute to knowledge in the field and push the boundaries of what we know about hEDS."
The lab now has many other members, from volunteers to interns to coordinators, who either have been diagnosed with hEDS or are close to someone who has been.
Underestimating hEDS
Often incorrectly believed to be a rare, non-serious condition, hEDS affects the entire body in significant ways. At least 1 in 500 people have the disease, well above the 1 in 3,000 threshold at which a disease is considered rare.
"The vast majority of patients have a terrible time managing their care because physicians simply don't believe hEDS is real, and they think it's all in their head." -- Dr. Russell "Chip" Norris
hEDS is a connective tissue disorder that causes joint and muscle pain, joint dislocation, gastrointestinal discomfort, sleep disturbances, tingling or other unpleasant sensations on the skin and a whole host of other symptoms. People with hEDS often experience these symptoms at varying levels of severity at different times, making the disease unpredictable. Managing the disease is estimated to cost patients more than $100,000 per year, with some having costs of over $1 million in that time frame. It is anything but benign, said Kautz.
"My goal is to make some small contribution to helping hEDS patients by understanding the mechanisms that lead to this disease." -- Dr. Heather Boger
Troublingly, half of all people with hEDS report considering suicide due to both the physical effects of the disease and the failure of care providers to recognize the disease, resulting in a lack of proper care to address pain, comorbidities and/or hEDS' myriad, often debilitating conditions.
"The vast majority of patients have a terrible time managing their care because physicians simply don't believe hEDS is real, and they think it's all in their head," said Norris.
One of the Blue Sky Award recipients' goals is to change damaging medical misconceptions about hEDS by elucidating the biological mechanisms underlying the disease. They also hope to assess the potential of VNS as a treatment for hEDS.
A new approach to hEDS
VNS is already used to treat stroke, which brought it to Kautz's attention. It's also used to treat everything from depression to Parkinson's disease. However, the MUSC team is one of the first to test it in hEDS.
The vagus nerve is one of the longest nerves in the body, starting in the brain and traveling to the abdomen. When stimulated, it can affect a variety of body systems and processes.
For this project, the team will use a novel technique for stimulating the vagus nerve to target a variety of symptoms in volunteers from their database of 7,000 hEDS patients.
"We're using an electrical form of brain stimulation that'll be applied to your ear," said Badran. "Our work over the last decade has suggested that stimulating that nerve in the ear activates parts of the brain that are influenced by activation of the vagus nerve."
"We're using an electrical form of brain stimulation that'll be applied to your ear. Our work over the last decade has suggested that stimulating that nerve in the ear activates parts of the brain that are influenced by activation of the vagus nerve." -- Dr. Bashar Badran
The team will also monitor patients' hEDS symptoms to see which ones are lessened by VNS.
To learn more about how hEDS symptoms develop and how VNS is affecting those symptoms, Boger will use VNS on mice with hEDS symptoms.
"My goal is to make some small contribution to helping hEDS patients by understanding the mechanisms that lead to this disease," said Boger.
"My hope is that this is the start of a bigger research program that would be able to look at hEDS from the animal model molecular level up to trials for improving quality of life for people with hEDS." -- Dr. Steven Kautz
In addition to understanding what is happening in the body during hEDS, the team also wants to understand why and how VNS helps to ease hEDS symptoms.
"We also need to understand why VNS could provide relief for these patients," Norris said. "When you start understanding treatment mechanisms, you have a lot more options for understanding the disease, which we know very little about."
Blue skies ahead
The dark days when hEDS was downplayed and misunderstood may soon give way to blue skies, thanks to this team's cutting-edge interdisciplinary research.
"It's really only at places like MUSC where you can bring together clinicians and researchers and basic scientists to put together a team that will start to lay the fundamental scientific groundwork for studies that can make a big impact in people's lives across the world," said Badran.
Several members of the team are already on the forefront of hEDS research, continuing to examine the genetic components of the disease. And there is much more on the horizon beyond the study funded by the Blue Sky Award.
"My hope is that this is the start of a bigger research program that would be able to look at hEDS from the animal model molecular level up to trials for improving quality of life for people with hEDS," said Kautz.
