UCLA researchers from the Department of Medicine have identified drug combinations that can speed up treatment of tuberculosis by being delivered intranasally as well as orally.
BACKGROUND: Tuberculosis (TB) is an airborne disease caused by the bacterium Mycobacterium tuberculosis, affecting more than 10 million people worldwide each year. The standard treatment for drug-sensitive TB involves a six-month course of combination antibiotics, while drug-resistant TB may require therapy lasting up to fifteen months or longer. These lengthy TB treatment regimens often result in serious side effects and increase the risk of drug resistance. Therefore, better therapies are critical to decrease treatment duration and to combat the emergence of drug-resistant TB.
INNOVATION: Researchers at UCLA have used an artificial intelligence-based approach to identify several combinations of drugs that can speed up TB treatment and shown that when part of one of the regimens is administered intranasally as well as orally, treatment is further accelerated. The combination of oral and inhalational therapy more rapidly reduces TB lung burden and shortens treatment duration necessary to achieve a relapse-free cure. UCLA researchers selected two antibiotics of one of the best Parabolic Response Surface oral regimens and delivered them intranasally into TB-infected mice on top of oral administration of the whole four-drug regimen. They found that intranasal administration of the antibiotics on top of oral administration improved treatment outcomes and accelerated relapse-free cure when compared to only oral administration of the regimen; the improvement in outcome was quantified through measurements of TB lung burden during treatment and 3 months after treatment was terminated to confirm that relapse-free cure had been obtained. In summary, UCLA researchers have identified a combination of TB antibiotics that can be administered intranasally as well as orally to TB-infected mice to improve treatment response and accelerate relapse-free cure. These findings provide potential for novel therapeutics against TB.
POTENTIAL APPLICATIONS:
- Treatment of TB
- Treatment of other bacterial lung diseases
- Methods for inhalational drug delivery
ADVANTAGES:
- Shortens TB treatment length
- Improves relapse-free cure
DEVELOPMENT-TO-DATE: UCLA researchers have tested the efficacy of adding intranasal administration of two drugs of a four-drug TB drug regimen on top of oral delivery of the entire four-drug TB drug regimen in a mouse model of pulmonary TB and demonstrated more rapid reduction in the lung burden of TB bacilli and faster attainment of relapse-free cure.
Related Papers (from the inventors only):
Lee, B.-Y., D.L. Clemens, S. Masleša-Galic, S. Nava, C.-Y. Lo. J.I. Zink, and M.A.
Horwitz. 2025. Adding intranasal to oral administration of an ultra-rapid near universal drug regimen accelerates relapse-free cure of tuberculosis in mice. J. Infect. Dis. Published online 11 June 2025. doi:https://doi.org/10.1093/infdis/jiaf315 https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaf315/8160502?utm_source=authortollfreelink&utm_campaign=jid&utm_medium=email&guestAccessKey=d3b91282-5e0c-4546-912e-3b93e297af5b
Horwitz, M.A., D.L. Clemens, and B-Y. Lee. 2019. AI-enabled parabolic response surface approach identifies ultra-short-course near-universal TB drug regimens. Adv. Therap. 3:1900086. Published online 19 Sept. 2019. PMCID: PMC6988120 https://onlinelibrary.wiley.com/doi/full/10.1002/adtp.201900086
Clemens, D.L., B-Y. Lee, A. Silva, B.J. Dillon, S. Masleša-Galić, S. Nava, X. Ding, C-M. Ho, and M.A. Horwitz. 2019. Artificial intelligence enabled parabolic response surface platform identifies ultra-rapid near-universal TB drug treatment regimens comprising approved drugs. PLoS One 14(5): e0215607. Published 10 May 2019. PMID: 31075149. PMCID: PMC6510528. doi: 10.1371/journal.pone.0215607. https://doi.org/10.1371/journal.pone.0215607
KEYWORDS: Intranasal, Inhalation therapy, Tuberculosis, Mycobacterium tuberculosis, artificial intelligence, Parabolic Response Surface, vehicle