A cure may be in sight for patients with achalasia, a condition that causes difficulty swallowing due to esophageal contractility issues.
Researchers at Vanderbilt University Medical Center have linked the rare condition to active varicella zoster virus in the esophagus, opening the door to antiviral treatment to alleviate symptoms.
“Prior therapies for this condition were all brute force palliative options such as cutting the muscle or using large dilators to break open the muscle in myotomies. But it didn’t actually cure the condition, and we knew patients at some point would get a repeat procedure,” explained Rishi Naik, M.D., an assistant professor of gastroenterology, hepatology and nutrition at Vanderbilt.
“By actually understanding the etiology of their conditions, we may now not only offer them a therapy, but a potential cure.”
Naik and colleagues are now enrolling in a Phase 3 clinical trial to test whether common shingles medications might benefit patients with achalasia and prevent virus reactivation.
Clues In Clinic
The work was born out of Vanderbilt’s Swallowing and Esophageal Disorders Center, where Naik treats the specialty conditions alongside Michael Vaezi, M.D., Ph.D., and Dyanesh Patel, M.D. and others.
Over time, the providers began to notice a trend among new patients.
“Listening to their stories, it wasn’t uncommon that someone had a prior or recent history of shingles and subsequently developed problems swallowing,” Naik said. “We started thinking that maybe the shingles virus was reactivating, causing achalasia.”
In a study investigating the association, Naik and colleagues found 12 of 15 older adults presenting to Vanderbilt with achalasia had detectable varicella zoster virus DNA in their saliva. The virus appeared to inhabit neurons beyond those that feed the characteristic skin rash associated with shingles. For some patients, the virus seemed to trigger swallowing issues instead.
Treatment Testing
Achalasia is rare: fewer than two adults per 100,000 globally have it, according to the team’s own published management guidelines. A large center is required for answers.
“Having such a high volume, we’re able to pick up on signals in a very rare condition,” Naik explained.
A high patient volume also allowed the researchers to tease apart achalasia subtypes. For their current trial, they’re enrolling adults with achalasia subtypes II and III, based on their findings that these patients tend to have higher viral loads and may benefit most from antiviral therapy.
Enrolled patients will self-administer valacyclovir three times daily for four months. The research team will reassess viral load, phenotype and reactivation one year later using non-invasive biologic samples. Halfway through the trial so far, Naik says he is seeing promise in terms of symptom relief for some participants, though more analysis is needed.
“We’re checking their saliva and blood for active virus. Long-term, we imagine any patient who comes in could undergo this kind of test to confirm diagnosis and then, in real-time, determine if they are a candidate for this already FDA-approved medication,” Naik said.
By gathering biologic samples, the researchers may also learn genetic factors that contribute to viral reactivation in the esophagus or the etiology behind other symptoms.
“It’s possible that other viruses may trigger other motility disorders. Moving forward, looking at all patients who have difficulties swallowing, maybe different viruses cause different symptoms,” Naik said.
More Options for Patients
The bottom line, Naik says, is that patients now have options.
“What we’re seeing overall is that early recognition of a rare condition allows us to really disrupt the therapeutic options,” he said. “Even if the diagnosis is not quite clear, is definitely worth sending over for consult, because the earlier in the process, the more likely patients are going to respond to therapeutics.”
Vanderbilt employs high-resolution manometry to aid rapid diagnosis of esophageal motility disorders. The cutting-edge technique measures pressures in the esophagus to determine sphincter function and the direction of peristalsis.
“Patients have options, and more are coming. I think we’re looking towards a cure for their condition.”
Following a diagnosis, the other current option for achalasia treatment is peroral endoscopic myotomy. The Vanderbilt team is participating in a multicenter, national randomized trial to better understand the efficacy of this contemporary approach in treating swallowing disorders. Naik says this includes cellular analyses and long-term follow up.
“Patients have options, and more are coming. I think we’re looking towards a cure for their condition. I think the patients have grown to be very helpful and understanding toward the need to develop a personalized approach for their disease processes,” Naik said.
