Tuberculosis and the Need for New Treatments

Global Impact of Tuberculosis

Tuberculosis (TB) affects millions worldwide. In 2017 alone, this bacterial disease claimed the lives of 1.6 million individuals and impacted countless others. Traditionally, TB is treated with antibiotics, but the lengthy treatment duration and the emergence of antibiotic-resistant strains necessitate alternative therapies.

Innovative Approaches to Treatment

Researchers are exploring TB treatments that do not depend on antibiotics. Some studies suggest that vitamins may play a role in preventing the disease. A research team from Ireland and the United Kingdom is investigating the potential of a derivative of Vitamin A, known as all-trans-retinoic acid (ATRA), as a treatment for tuberculosis. Previous research indicated that ATRA could effectively kill TB bacteria by activating the immune system to eliminate invasive bacterial cells.

Development of Inhalable ATRA Microparticles

Research Objectives

The Irish researchers aimed to enhance the administration of ATRA by formulating it into inhalable microparticles. This method would allow the drug to be delivered directly to the lungs, the primary site of TB infection, thereby optimizing its therapeutic effect.

Experimental Methodology

The study involved infecting mice with tuberculosis and allowing the bacteria to proliferate in their lungs for two weeks. Subsequently, the researchers administered the drug directly into the windpipe of the infected mice, simulating inhalation via an inhaler. This process was repeated every two days, and the mice were euthanized and dissected after three doses to evaluate the treatment’s impact.

Results of the Study

Typically, TB bacteria cluster in the lungs, leading to the formation of lesions that impair lung function. The treatment with ATRA microparticles significantly reduced the size of these lesions and decreased the number of viable TB bacteria by nearly 99%. Concerns about the effectiveness of ATRA in microparticle form compared to its standalone form were addressed; the results indicated that the microparticle formulation did not diminish ATRA’s efficacy.

Future Directions for ATRA Microparticles

Clinical Testing Ahead

This study presents a promising inhalable treatment option for tuberculosis that does not rely on antibiotics, making it potentially effective even against antibiotic-resistant strains. However, further clinical trials in human patients are essential to validate the safety and efficacy of this innovative treatment.

References

O’Connor, G., Krishnan, N., Fagan-Murphy, A., Cassidy, J., O’Leary, S., Robertson, B. D., Keane, J., O’Sullivan, M. P. & Cryan, S.-A. Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-Retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis infection. European Journal of Pharmaceutics and Biopharmaceutics 134, 153-165 (2019). https://doi.org/10.1016/j.ejpb.2018.10.020

RCSI researchers develop new tuberculosis treatment. Royal College of Surgeons in Ireland. http://www.rcsi.ie/index.jsp?p=100&n=110&a=11709