February 26, 2024
Respiratory syncytial virus (RSV) causes lower respiratory tract infection in millions each year and is the leading cause of hospitalization in young children. It is also responsible for over a hundred thousand hospitalizations each year among the immunocompromised and the elderly. Sam Lai, Ph.D., professor in the Division of Pharmacoengineering and Molecular Pharmaceutics at the UNC Eshelman School of Pharmacy, and his lab, have created an inhaled “muco-trapping” monoclonal antibody that effectively treats RSV infections, called Mota-MT.
“Building off of our experience with COVID and the challenge that comes with vaccine hesitancy, our team was motivated to explore an alternate strategy for treating RSV,” said Lai.
A number of RSV vaccines have been approved the past 12 months, but their long-term efficacy and safety still need to be determined. In addition, less than 10% of eligible adults have elected to get vaccinated, underscoring the continued need for treatment that can be given soon after symptoms emerge. There have also been many failed investigational therapies for RSV that were administered by systemic or oral dosing, which didn’t address the fact that RSV is primarily confined to the airways. This means that no RSV treatment is currently available.
This led Lai’s team to develop an inhaled therapy that fights RSV directly in the airways. They showed the molecule – Mota-MT – can effectively immobilize RSV in fresh human airway mucus. In large animal studies, inhaled Mota-MT was able to eliminate infectious viral titers to non-detectable levels within just three days, and reverse inflammation and bronchiolitis in the lung to levels comparable to uninfected animals, despite only initiating treatment when the lung is already heavily infected. The inhaled treatment of Mota-MT may offer faster symptom relief and reduce rates of RSV-hospitalization since the treatment can be taken at home soon following diagnosis, using a handheld nebulizer, without arranging to visit a health care office. Their research was recently published in Advanced Science and is moving on to Phase 1 clinical trial this year.
“A safe, effective and easy-to-dose treatment is sorely needed for RSV,” said Lai. “Most prior efforts with small molecule antivirals ultimately proved to be unsafe in the most vulnerable populations. We are excited not only by the prospect of a treatment that could benefit millions each year, but also by the outstanding safety profile with antiviral antibodies. It greatly reduces the clinical development risks. We hope to obtain key clinical proof-of-concept within the next two years.”
Lai’s research spans the interface of immunology and engineering, with a particular emphasis on developing novel bioactive molecules that can better reinforce mucosal health. A decade ago, his lab discovered that antibody molecules can be tuned to interact with mucins, the key building block of mucus that gives it its sticky texture. This allows antibodies to bind bacteria or virus at mucosal surfaces, trap them in mucus and block the spread of the infection. Alison Schaefer, a Ph.D. student in biomedical engineering, is a co-first author on the work, which also involved various collaborators at Carolina including Anthony Hickey, Ph.D., Raymond Pickles, Ph.D., and Priya Kumar, M.D. Inhalon Biopharma has licensed the technology and is leading the clinical development efforts.
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