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Latent tuberculosis: is there a role for thioridazine?
1Tuberculosis Research Laboratory 151, Department of Veterans Affairs Medical Center, 5901 East Seventh Street, Long Beach, CA 90822, USA. Chuck.Sohaskey@va.gov
Recent Patents on Anti-Infective Drug Discovery
|May 10, 2011
Summary
Thioridazine effectively targets dormant Mycobacterium tuberculosis in latent tuberculosis models. This inexpensive drug shows promise for treating drug-resistant tuberculosis, potentially offering a new therapeutic avenue.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Tuberculosis (TB) affects one-third of the global population, primarily as latent infection.
- Latent TB is characterized by a positive tuberculin response without active symptoms.
- Current treatment challenges include the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB.
Purpose of the Study:
- To investigate the efficacy of thioridazine against latent Mycobacterium tuberculosis.
- To evaluate thioridazine as a potential treatment for drug-resistant latent TB.
- To explore the advantages of thioridazine in combating MDR/XDR TB.
Main Methods:
- Utilized in vivo murine models and the in vitro Wayne model to study latent TB.
- Observed the respiratory profile changes of M. tuberculosis during the shift to a non-replicating state.
- Assessed the sensitivity of dormant M. tuberculosis to thioridazine.
Main Results:
- Dormant M. tuberculosis in both models demonstrated sensitivity to thioridazine.
- Thioridazine's primary target is the respiration of M. tuberculosis.
- Thioridazine is inexpensive, well-characterized, and unlikely to induce further drug resistance.
Conclusions:
- Thioridazine presents a viable option for treating drug-resistant latent tuberculosis, alone or in combination therapy.
- Its low cost, effectiveness against resistant strains, and favorable resistance profile make it attractive.
- Further research into thioridazine analogs suggests potential for future MDR/XDR TB treatments.
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