Research into the development of reflux treatments that specifically target pepsin was discussed recently on Fox News 92.5, a US radio station broadcasting news and talk programming.
The discussion featured Dr Nikki Johnston, Professor of Otolaryngology at the Medical College of Wisconsin, in conversation with Jason Lewis, a former US Congressman and radio host.
Dr Johnston has spent much of her academic career investigating the role of pepsin in reflux-related disease, particularly laryngopharyngeal reflux (LPR), often referred to as silent reflux. She is also a co-founder of N-Zyme Biomedical, which is developing pepsin-targeted treatments.
During the chat, she outlined a therapy currently in clinical development that aims to inhibit pepsin directly, rather than focusing solely on suppressing gastric acid.
Pepsin and reflux-related tissue damage
Pepsin is a digestive enzyme produced in the stomach to help break down food. In reflux, it can move upwards with stomach contents and be left behind in the throat and airway.
Even when acid is reduced, pepsin can remain active. Research shows it can be absorbed by cells in the throat and continue to cause irritation and inflammation, even in non-acid reflux.
As Dr Johnston explained during the broadcast: “Pepsin, which is the main digestive enzyme in the stomach, is actually taken up by the cells and transported through parts of the cell where it becomes reactivated. This is a novel mechanism by which pepsin induces cellular injury independent of the acidity, and therefore independent of taking a PPI.”
This helps explain why many people with LPR continue to experience throat symptoms despite taking acid-suppressing medication.
A different therapeutic approach
Dr Johnston’s team has identified that fosamprenavir, a drug originally developed for HIV treatment, can bind to and inhibit pepsin. Rather than eliminating pepsin entirely, which would interfere with normal digestion, the aim is to prevent pepsin from causing harm when it reaches sensitive tissues outside the stomach.
N-Zyme is developing both systemic and locally delivered formulations of the drug. One approach under investigation involves delivering a low dose directly to the throat, where LPR-related injury occurs. Because the larynx and upper airway are readily accessible, local delivery may allow effective treatment while minimising overall drug exposure.
In related work, Dr Johnston has also explored inhaler-based approaches to deliver treatment directly to laryngeal tissues in LPR, building on the same principle of targeting pepsin-related injury at the site of damage.
Discussing the research on air, Dr Johnston highlighted that this strategy could be particularly relevant for patients whose throat symptoms have failed to improve with standard reflux medications.
“About 80 per cent of patients with LPR, or silent reflux, do not respond to acid suppression PPI medication,” she explained.
Clinical development, not clinical use
The therapy discussed during the broadcast remains in clinical development, with patient enrolment for trials beginning in the US. It is not yet approved for routine clinical use, and further studies are needed to establish safety and effectiveness.
Nevertheless, the work reflects a growing recognition within reflux research that pepsin plays a central role in ongoing disease, particularly in conditions such as LPR where acid suppression alone has clear limitations.
Reflux affects tens of millions of people worldwide, and long-term pepsin exposure has been associated with chronic throat symptoms, airway inflammation and more serious complications, including an increased risk of laryngeal cancer.
As research continues, pepsin-focused treatments represent an important area of investigation, particularly for patients with persistent symptoms who have not responded to conventional acid-based approaches.
Pepsin and reflux testing
At Peptest, pepsin is recognised as a key biomarker of reflux. Our Peptest diagnostic test detects pepsin in saliva, helping clinicians identify reflux events, including non-acid reflux, that may otherwise be missed.
Understanding whether pepsin is present can play an important role in the assessment of reflux-related symptoms and in guiding further investigation and management, particularly in suspected LPR. Learn more about how Peptest detects pepsin and what a positive result means: The Role of Pepsin in Reflux
Peptest detects pepsin — the stomach enzyme that marks reflux — in a saliva sample. Collected at home, analysed in our UK laboratory, results back within 48 hours.
- Results in 48 hours
- No GP referral needed
- UK laboratory
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