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May 2026Some breakthroughs come from the bench. Others bubble up from the bottom.
The first are built via decades of research by dedicated scientists who construct and test hypotheses and connections using the scientific method. The second take shape when persistent patients push physicians to consider possibilities beyond what they learned in medical school.
Both can result in practice-changing paradigm shifts.
Currently, otolaryngology is considering the potential impact of two emerging innovations: gene therapy for auditory and vestibular disorders and growing recognition and acceptance of retrograde cricopharyngeal dysfunction (RCPD), colloquially known as “can’t burp syndrome.” Gene therapy, of course, is the result of decades of rigorous research and has moved from the laboratory outward. RCPD moved in the opposite direction, gaining momentum after patients connected on Reddit and pressed clinicians to consider a symptom cluster that had long been overlooked.
Otolaryngologists are both curious and cautious—excited to help patients, eager to understand the science, and already exploring implications for the future.
The Dawn of Intracochlear Restorative Medicine
By year’s end, the U.S. Food and Drug Administration is expected to approve the first gene therapy for hearing loss (Prime Therapeutics. https://tinyurl.com/md62d3n2), and otolaryngology may officially enter the era of intracochlear restorative medicine. [After the May issue went to press, the FDA approved Regeneron’s gene therapy on April 23, 2026.]
Regeneron Pharmaceuticals is seeking regulatory approval of DB-OTO (BioSpace. https://tinyurl.com/4cz62rva; Biopharmadive. https://tinyurl.com/muyss2z2), a dual adeno-associated virus (AAV) gene therapy that delivers a functional copy of the otoferlin (OTOF) gene to inner hair cells in the cochlea and has been shown in clinical trials to dramatically improve hearing in children with OTOF-related deafness. Nine of 12 children who received DB-OTO during the first-in-human registrational study of the therapy achieved clinically meaningful improvements in hearing by 24 weeks. Six could hear soft speech without assistive devices, and three achieved normal hearing sensitivity (N Engl J Med. doi:10.1056/NEJMoa2400521).
“What’s truly remarkable is that suddenly, within one month after the delivery of the gene into the ears of human children, they went from completely deaf to sensing sound,” said Zheng-Yi Chen, DPhil, an associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear and associated professor of otolaryngology–head and neck surgery at Harvard Medical School, both in Boston, who was involved in the very first trial to test the efficacy of gene therapy in treating OTOF-related congenital deafness.
In that study, published in The Lancet in 2024, five of six children demonstrated substantial hearing recovery, with ABR thresholds improving by 40–57 dB at speech frequencies (Lancet. 2024;403(10441):2317-2325).
“The earliest injected patients are now past three years, and their hearing almost matches the normal level. And they can have a conversation. Now they hear, they can speak, they understand,” Dr. Chen said.
In little more than a decade, gene therapy for hearing loss has progressed from a hard-to-fund idea to a viable clinical reality.
From First Success to Broader Possibilities
“The first grants I put in for developing gene therapy for hearing loss were not well received,” said Gwenaelle S. Géléoc, PhD, an associate professor of otolaryngology–head and neck surgery at Harvard Medical, who has been researching gene therapy for approximately 12 years. “The idea was that there were therapies available—hearing aids and cochlear implants—so gene therapy just wasn’t needed. But although cochlear implants are great technology, they’re not perfect. A lot of patients don’t do well with them and in fact end up not using them.”
Device-aided hearing is also not the same as biological hearing. Hearing aids and cochlear implants provide access to sound, but cochlear implants, in particular, do not recreate the nuanced frequency discrimination, sound localization, or speech perception in noise that characterize typical hearing.
That’s one reason researchers continued to pursue gene therapy, despite the widespread availability of auditory aids. The other was the potential to truly revolutionize the treatment of hearing loss, a condition affecting approximately one out of seven people in the U.S. (Hearing Loss Association of America. https://tinyurl.com/nd5ydp98), and more than 430 million people globally (World Health Organization. https://tinyurl.com/nw4vfezt).
Congenital deafness affects 1.7 per 1,000 babies born in the U.S.—a prevalence on par with Down syndrome and substantially higher than many rare genetic disorders (N Engl J Med. doi:10.1056/NEJMoa2400521; National Institute on Deafness and Other Communication Disorders. https://tinyurl.com/h3fkz7ze; Down Syndrome Education International. https://tinyurl.com/mt8bdp9s). More than half of those cases are related to genetic alterations (University of Miami Miller School of Medicine. https://tinyurl.com/49sxt5k7). OTOF-related deafness only accounts for one to three percent of cases of congenital deafness, but it was an attractive target for researchers because cochlear hair cells remain structurally intact.
“Gene therapy doesn’t restore structure; it restores that function of a cell that lacks a protein from a genetic defect,” said John Greinwald, MD, professor of otolaryngology–head and neck surgery and director of genetics of the division of pediatric otolaryngology at the Cincinnati College of Medicine in Ohio.
The ear itself is also an attractive target for gene therapy because it is a “privileged organ,” Dr. Greinwald said. “You can deliver therapy directly to the ear without making it systemic.”
The therapy that is approaching approval is only for OTOF-related deafness; however, researchers are already working on genetic therapy for other forms of deafness, including GJB2-related hearing loss, Usher syndrome, and even autosomal dominant deafness-41 and autosomal dominant deafness-2A (Hear Res. doi:10.1016/j.heares.2020.107932; Advances in Motion. https://tinyurl.com/6r9jc9ms). Researchers are also investigating the use of other delivery methods for gene therapy.
“AAV vectors have a small packaging capacity, so large genes cannot fit. Think about trying to squeeze an elephant into a MINI Cooper!” Dr. Géléoc said. “In our lab, we’re using a different approach to target these large genes. We design short antisense oligonucleotide sequences (ASOs), which are short strings of DNA, to target a specific region of a gene. We use these ASOs as a molecular bandage covering the deleterious mutation and restoring expression of the protein.”
Beyond a Single Gene: Implications for Practice
Already, Dr. Chen is getting multiple emails from parents, wondering if they should pursue cochlear implantation for their children or seek gene therapy. At present, gene therapy is not a practical alternative for most children: Approval of the first candidate is still pending, additional therapies remain in clinical development, and eligibility is limited to patients with particular genetic mutations. But the field is evolving quickly and already affecting practice.
The advent of genetic therapy for hearing loss is likely to lead to an increase in genetic testing; in fact, genetic testing may become the standard of care for infants who fail their newborn hearing screening. Some clinicians believe the advent of gene therapy may also prompt reconsideration of newborn hearing screening protocols. Because certain forms of genetic deafness—such as OTOF-related auditory neuropathy—can be missed by otoacoustic emission (OAE)-based screening alone, broader use of automated auditory brainstem response (AABR) testing may warrant discussion as treatment options expand.
“This may change the paradigm of how we screen newborns,” Dr. Greinwald said.
Researchers and clinicians also expect to see an explosion of new treatment options over the next five to 10 years as scientists develop and test therapies to target additional genetic causes of hearing loss.
“I think we are soon moving into a new era where patients with hearing loss will have the option of no treatment, hearing aids, cochlear implants, or gene therapy,” Dr. Géléoc said, noting that cochlear implantation will remain an important option for patients who have severe hearing loss that is not amenable to gene therapy.
Experience to date also suggests that the window for intervention may be broader than previously assumed. In clinical trials, children treated well beyond infancy—including two participants who were 16 years old at the time of intervention—demonstrated measurable improvements in hearing in the treated ear. Although long-term language outcomes remain under study, early findings suggest that auditory and speech perception gains may be possible even in patients treated later than the age historically considered optimal for intervention.
Best practices will likely still emphasize early detection and early intervention, however. Dr. Greinwald foresees a not-too-distant future in which newborns who do not pass their initial hearing screening are quickly referred for diagnostic ABR testing, followed by early otolaryngology evaluation, genetic testing, and any additional workups. By three months of age, he says, families and clinicians will be encouraged with targeted genetic intervention—if a treatable mutation is identified and the family elects to proceed.
“This is the dawn of intracochlear restorative medicine,” Dr. Greinwald said. Otolaryngology is moving from assistive technologies toward biological correction of disease.
A very different kind of restorative breakthrough is unfolding in laryngology, where retrograde cricopharyngeal dysfunction (RCPD) has emerged from online patient communities to become a condition that can, in many cases, be effectively cured.
RCPD: Recognition in the Age of Reddit
Nancy Jiang, MD, a clinical associate professor of otolaryngology–head and neck surgery at Stanford University School of Medicine, in Stanford, Calif., encountered her first patient with retrograde cricopharyngeal dysfunction (RCPD), otherwise known as “can’t burp syndrome,” in 2019. The patient told her about the condition; Dr. Jiang, like most other physicians at the time, had never heard of “can’t burp syndrome.” When she looked for more information, she found a 2019 OTO Open paper by Robert Bastian, MD, “Inability to Belch and Associated Symptoms due to Retrograde Cricopharyngeal Dysfunction: Diagnosis and Treatment,” the first paper to propose RCPD as a distinct clinical syndrome and to demonstrate that the symptom complex was both diagnosable and treatable (OTO Open. doi:10.1177/2473974X19834553).
“I was extremely skeptical,” Dr. Jiang said, “and I almost fell off my chair laughing when I read that patients were coming from Reddit.”
Indeed, the first patient Dr. Bastian treated was a young man who’d experienced a lifetime of uncomfortable bloating, gurgling, and inability to burp that interfered with his daily life. Ten other physicians dismissed his symptoms and complaints.
“Nobody seemed to believe me that this problem even existed,” the patient later told Undark magazine (Undark. https://tinyurl.com/dk8kkvu6).
He approached Dr. Bastian after seeing an online video in which the otolaryngologist described using botulinum toxin to treat certain throat disorders. He asked whether the same treatment might help him. Dr. Bastian injected the patient’s cricopharyngeus muscle with botulinum toxin, and his symptoms soon subsided. The patient was so pleased that he shared his experience on Reddit. His post attracted the interest of others with similar symptoms—some of whom sought out Dr. Bastian for treatment. By the time he published his paper, he’d treated 121 individuals.
Today, the Reddit “r/noburp” forum (established in 2014) has more than 17,000 members, and awareness of “no burp syndrome” is spreading both on TikTok and at otolaryngology conferences.
“It quickly went viral in the field of otolaryngology because, I think, we were all seeing patients start to pop up in our clinics with questions about this,” Dr. Jiang said. Awareness is still largely confined to laryngologists, however.
From Symptom Cluster to Clinical Entity
RCPD is defined by an easily recognizable symptom cluster: a lifelong inability to belch, along with a consistent history of gastrointestinal bloating, flatulence, and chest or throat gurgling. These symptoms typically cause significant distress and discomfort, often impacting affected individuals’ social and professional lives.
To relieve the discomfort and pressure, some patients “make themselves ‘air vomit,’ where they stick a finger down their throat to trigger the gag reflex and let the sphincter open,” said Tom Carroll, MD, director of the Brigham and Women’s Hospital program for Voice, Swallowing, and Upper Airway in Boston. Patients also report intolerance and avoidance of carbonated drinks.
Many, like Dr. Bastian’s initial patient, have seen multiple physicians over the years and have undergone extensive gastrointestinal testing. These tests may reveal gastric air distention or a lax esophagus, but are usually otherwise unremarkable. Research studies have shown that when patients with suspected RCPD undergo high-resolution impedance manometry during a carbonated drink challenge, they demonstrate abnormal air movement and elevated upper esophageal sphincter pressures consistent with impaired retrograde gas venting (Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2024.12.014; Laryngoscope. doi:10.1002/lary.31811); however, manometry is not currently recommended or required for diagnosis.
At present, diagnosis is based on clinical history and symptoms. If the patient has ever been able to burp, it’s not RCPD, Dr. Carroll said. Such patients should be evaluated further.
Injection of botulinum toxin into the cricopharyngeus muscle can be life-changing—and, it appears, possibly life-lasting—for affected patients, for reasons that aren’t yet fully understood. The physiological effects of botulinum toxin only persist for a few months, but patients who experience symptom relief after injection often maintain the ability to belch long after treatment.
One working theory is that affected individuals’ “brain pathways decided to eliminate this normal reflexive thing for some reason,” Dr. Carroll said. Botulinum toxin injection into the cricopharyngeus muscle reduces sphincter tone, allowing easier venting of trapped gas. As the toxin’s effect wears off, individuals may learn how to voluntarily control the muscles and initiate belching.
“I’ll be the first to tell you that I don’t fully understand what we’re doing right now. It doesn’t make any sense,” said Joshua Schindler, MD, associate professor of otolaryngology and division chief of laryngology at Oregon Health and Science University in Portland, Ore. He treated his first patient with suspected RCPD in 2019 after reviewing the Bastian paper and concluding that the potential benefit outweighed the risk. The patient was thrilled with the result.
“She said everything in her life was better,” Dr. Schindler said. He’s since treated numerous other RCPD cases—sometimes as many as four a day—with 95% of his referrals coming from Reddit, he said.
Beyond Anecdotes: Implications for Practice
RCPD remains an emerging diagnosis without established evidence-based treatment algorithms. Botulinum toxin dosing varies from practitioner to practitioner, based on personal experience and anecdotal evidence. Currently reported dosing practices range from 50 units of botulinum toxin to 100 units or more. Some patients come in requesting specific doses, which, understandably, leads some physicians to ask, “Who’s running this?”
Most patients—approximately 70%, according to Dr. Carroll—only require one injection, on one side of the muscle, for sustained relief. About half of those who can’t satisfactorily belch after receiving one injection will experience relief after a second injection of botulinum toxin to the other side of the muscle.
Those numbers, though, may not be accurate or reflective of wider practice. That’s why Dr. Carroll and others have initiated a multicenter, prospective survey-based study to assess patients’ symptoms before and up to a year after injection.
“We need more data,” he said. “We need to understand the natural course of this because currently, we meet these people once and never see a lot of them again.”
Ideally, physicians and scientists would also rigorously test the effectiveness of botulinum toxin for RCPD in clinical trials. But that’s extremely difficult to do in an era where patients trumpet the success of their treatment online.
“The moment that gets done, science is very hard to accomplish because nobody wants to enter a placebo-controlled randomized trial where they have to undergo general anesthesia and they may or may not get the drug,” Dr. Schindler said.
Otolaryngology—and medicine at large—needs to figure out how to responsibly deal with social media-driven diagnoses and requests, as this trend shows no signs of abating. Dr. Jiang recommends beginning by listening to patients.
“These patients are suffering. Don’t dismiss them and don’t downplay their symptoms,” she said.
At the same time, physicians need to approach emerging diagnoses and treatments with curiosity and caution in equal measure. As noted in a recent JAMA Otolaryngology–Head and Neck Surgery article, “it remains essential to emphasize that online symptom recognition should prompt evaluation rather than replace it” (JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2025.5216).
It is on individual otolaryngologists and the otolaryngology community at large to balance openness to patient-driven discovery with the discipline of scientific validation. Some breakthroughs begin at the bench; others bubble up from patients. Both deserve careful listening, careful study, and careful stewardship.
Jennifer Fink is a freelance medical writer based in Wisconsin.
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