After days of wearing a device that stimulated nerves by her left ear, Jennifer Iacono, 29, of Columbia had an epiphany.

“My brain has been reset to the original factory settings, is the best way to describe it,” she said, clear of the brain fog, memory problems and even some of the chronic pain that normally clouds her mind. “My brain is so quiet. I didn’t realize how much noise I had until it got turned off.”

Her remarkable response, as well as others, to a noninvasive and deceptively simple treatment is one reason researchers at the Medical University of South Carolina are excited about a clinical trial there for patients with an overlooked and underdiagnosed disease that plagues young women.

Called hypermobile Ehlers-Danlos syndrome or hEDS, it is primarily a connective tissue disorder once dismissed as relatively benign disease of loose joints and skin and relatively rare. It is actually far more prevalent than previously believed, affecting maybe 1 in 500 and can affect major organs like the heart and the digestive system as well as causing chronic pain, fatigue and major autoimmune problems. More than 90 percent of those affected are female and more than three-quarters have a family history of it.

The most common problems are chronic pain and joint dislocations, abnormal scarring and more than a third have heart issues. But they are also more likely to have major problems with the gut and many suffer from a debilitating heart condition called postural orthostatic tachycardia syndrome or POTS. That array of symptoms is one of the things that prevents patients from getting the correct diagnosis and treatment, said Russell “Chip” Norris, whose lab at MUSC has become a major source of research into the genetic causes and impact of the disease.

“When you deal with that patient population, it’s almost overwhelming,” he said. “How do you develop something that can treat these patients because they are so different?”

The autonomic nervous system, which affects many of the body responses that happen involuntarily, like breathing and heart rate, is also involved in many of the bodily functions that appear to go awry with hEDS. A major component of the autonomic nervous system is the vagus nerve, the longest nerve in the body, which connects the brain to major organs like the heart and gut as well as the central nervous system. And that nerve and nervous system is where the MUSC team is focusing.

MUSC has used non-invasive stimulation of the vagus nerve to help premature newborns learn how to feed, and others to fight drug withdrawal symptoms, a treatment that is also being tried in adults with chronic pain and opioid withdrawal. Dr. Bashar Badran, whose Neuro-X Lab at MUSC has been collaborating on many of the nerve stimulation trials, likens the vagus nerve to a master control switch.

“It is an activator of an entire system,” he said. And, with such broad effects, it could allow the therapy to have a diverse impact. In this clinical trial, there are a broad range of symptoms they know patients can have, which would also include fatigue, depression, anxiety and gastrointestinal issues.

“So we thought we should test all of them,” Badran said. “The best way to do that is via diffuse therapeutics like this where you just place it on the ear.”

And it appears to be low-risk so far.

“It’s safe,” Badran said. “And it is relatively inexpensive.”

It is a double-blinded study, so neither the patients nor the researchers know if the patient is getting the real treatment or a simulation. The patients wear the device for a couple of hours each day for four weeks, and all will definitely get the stimulation for half of that time, meaning some will get two weeks and some will get four.

One of the advantages of this system is it is wearable and can be done at home, meaning patients don’t have to keep coming back to the clinic to receive treatment, said Steven Kautz, chair of the Department of Health Sciences and Research in the College of Health Professions at MUSC and a stroke and neurorehabilitation researcher.

He is part of the team that recently received a second year of funding from MUSC to continue the research, which for now involves patients in South Carolina. But they already have a waiting list of 30 patients who live outside the state and they are proposing a pilot project that involves mailing the equipment and virtual guidance. That data could allow them to propose a much broader expansion.

“We want to get the data so we can convince the funding agencies this is a scalable solution for people nationwide,” Kautz said. The researchers have a grant proposal before the Advanced Research Projects Agency for Health, or ARPA-H, a federal agency looking to provide accelerated funding for transformative health research. The MUSC researchers are applying for a program that focuses on women’s health that they hope could start in the fall.

While the trial is ongoing and they are still collecting data, they have some early “signals” that the stimulation may be having an effect, Badran said. These appear to be with easing symptoms with gut dysfunction and chronic pain. But it could be having an overall effect of pulling a dysfunctional nervous system back into a healthy state, Kautz said.

“If you can renormalize it, it can be a lasting effect,” he said.

This is personal for Kautz. His daughter, Emma, has hEDS and went from being a bright 9th grader with plans on becoming a trauma surgeon to now being bed-ridden with chronic pain and other maladies.

Part of the cruelty of the disease is physicians don’t know about it or don’t take it seriously, Kautz said.

The girls have been “told by their doctors that it is in their head and that they are not tough enough, they need to be tougher and do more,” he said.

“Especially when you have a young teenage girl, the dismissal of the patient’s symptoms is really enormous,” Norris said, and has an impact.

Many go years before they get the correct diagnosis. Iacono, nearing 30, has been affected by it her whole life but only received her diagnosis a few years ago.

One reason it is easy to dismiss, the researchers believe, is that it primarily affects women.

If it were a syndrome that affected young men, sidelining the quarterback of the football team as suddenly bed-ridden, “there would have been a war on this disease 50 years ago because it would have been seen as such a horrible problem,” Kautz said.

It also wears on the families when doctors cannot provide them hope for something better. Kautz hopes this is it.

“I’m super-excited that this could be the kind of thing that moves the needle,” he said.