Nav: Home

Statins cut tuberculosis treatment time in mice

March 15, 2016

In a study using mice, the Johns Hopkins University School of Medicine infectious disease experts have added to evidence that statin drugs -- known primarily for their cholesterol-lowering effects -- can significantly reduce the time it takes to clear tuberculosis infection.

"If our results hold up in humans, the use of statins as adjuncts to standard drug treatment could confer substantial benefits to public health and the nearly nine million new TB patients diagnosed worldwide each year," says study author Petros Karakousis, M.D., associate professor of medicine in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine. "Because statins like the one we tested are already approved by the U.S. Food and Drug Administration and have a long history of safety in patients, the new data might substantially accelerate their repurposing for tuberculosis patients."

First-line treatment for tuberculosis, which consists of a combination of four antibiotics, should in theory cure all drug-susceptible infections if strict compliance can be assured. However, says Karakousis, a curative course of treatment usually requires six to nine months, with a minimum of 18 months for drug-resistant forms of the lung disease. To assure compliance, most patients in developed countries undergo directly observed therapy, in which a trained health care worker provides the prescribed drugs and watches patients swallow every dose -- a strategy that mitigates spread of the disease but diverts resources from other needed medical care. In many developing countries, patients stop taking their antibiotics early when their symptoms abate, contributing to continued spread of tuberculosis in the community and the emerging problem of drug resistance.

Because new drugs that might shorten treatment duration are few in number and years from clinical use, Karakousis says his team's focus has been on repurposing already approved medicines that bolster the first-line regimen.

Toward that goal, the researchers focused on simvastatin, used by millions in the U.S. alone to reduce heart disease risk. In recent years, evidence has emerged that statins work, in part, by reducing inflammation by modulating the immune system, says Karakousis' colleague and study author Noton Dutta, Ph.D., research associate in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine.

In a report published just days before World TB Day by the Journal of Antimicrobial Chemotherapy, the Johns Hopkins team described its initial experiments with TB-infected cells growing in petri dishes. The researchers found that statins didn't directly kill the tuberculosis bacterium, but the addition of statin to infected cells helps stop bacterial growth. The combination of statins and standard drugs cleared the tuberculosis bacteria more efficiently than cells receiving just the usual drugs.

Moving to infected mice, the researchers gave either the first-line regimen or those drugs plus simvastatin to animals six weeks after they were exposed to the tuberculosis bacteria in doses analogous to those standard for human patients. By counting the number of bacteria that remained in the animals' lungs over the course of treatment, the researchers found that adding the statin reduced the time to infection-free lungs from 4.5 months to 3.5 months.

Similarly, after 2.5 months, 3.5 months and 4.5 months of the standard treatment, mice had infection relapse rates of 100 percent, 50 percent and 0 percent. Adding simvastatin lowered the relapse rate to 50 percent after 2.5 months and to 20 percent after 3.5 months.

Together, says Karakousis, the results suggest that simvastatin could be an attractive candidate drug to reduce the amount of time patients with tuberculosis must be treated with the standard regimen, and he adds that preliminary data also suggest that other statins have similar effects. Consequently, he and his colleagues are currently studying other members of this class of drugs to identify the most effective statin for adjunctive therapy and the most effective dose.

Other important considerations in selecting the optimal statin, he adds, include cost and the potential for drug interactions with antiretroviral drugs used to treat HIV infection, which is common in patients with tuberculosis in many parts of the world.

The World Health Organization estimates that the cost of standard tuberculosis treatment is about $2,000 per patient in industrialized countries, but that amount rises more than a hundredfold for patients with drug-resistant strains of the disease. Statins vary widely in cost, with some generic versions costing as little as $4 per month through discount programs run by major chain stores to more than $600 per month for name-brand drugs not covered by insurance. In general, statins are well-tolerated by most patients. Severe side effects, such as liver or muscle damage, are extremely rare.
Michael Pinn of Johns Hopkins also participated in this research. The study also includes researchers from the Public Health Research Institute, New Jersey Medical School, Rutgers University and the State University of New Jersey.

Funding support for this study was provided by the National Institute of Allergy and Infectious Diseases, the AIDS Clinical Trials Group, and the Johns Hopkins University Center for AIDS Research.

Johns Hopkins Medicine

Related Tuberculosis Articles:

Old target, new mechanism for overcoming tuberculosis resistance
In strains of tuberculosis that have developed drug resistance mutations, researchers have identified a secondary pathway that can be activated to reinstate drug sensitivity.
Researchers use tiny 3-D spheres to combat tuberculosis
Researchers at the University of Southampton have developed a new 3-D system to study human infection in the laboratory.
How the tuberculosis vaccine may protect against other diseases
The tuberculosis vaccine is well known to help protect against other infectious diseases, as well as cancer, but the exact mechanisms have not been clear.
Tuberculosis bacteria find their ecological niche
An international team of researchers have isolated and analyzed genetically tuberculosis bacteria from several thousand patients from over a hundred countries.
Tuberculosis and HIV co-infection
The HIV virus increases the potency of the tuberculosis bacterium (Mtb) by affecting a central function of the immune system.
Scientists explain why Russian tuberculosis is the most infectious
Scientists conducted a large-scale analysis of the proteins and genomes of mycobacterium tuberculosis strains that are common in Russia and countries of the former Soviet Union and found features that provide a possible explanation for their epidemiological success.
Tuberculosis elimination at stake
New data released by the European Centre for Disease Prevention and Control and WHO/Europe show that an estimated 340,000 Europeans developed tuberculosis in 2014, corresponding to a rate of 37 cases per 100,000 population.
Curcumin may help overcome drug-resistant tuberculosis
New research indicates that curcumin -- a substance in turmeric that is best known as one of the main components of curry powder -- may help fight drug-resistant tuberculosis.
Stopping tuberculosis requires new strategy
Unless there is a major shift in the way the world fights tuberculosis -- from a reliance on biomedical solutions to an approach that combines biomedical interventions with social actions -- the epidemic and drug resistance will worsen, say researchers at Harvard T.H.
Tulane researchers working on new tuberculosis vaccine
Researchers at the Tulane National Primate Research Center are leading efforts to find a new vaccine for tuberculosis, one of the world's deadliest diseases.

Related Tuberculosis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Moving Forward
When the life you've built slips out of your grasp, you're often told it's best to move on. But is that true? Instead of forgetting the past, TED speakers describe how we can move forward with it. Guests include writers Nora McInerny and Suleika Jaouad, and human rights advocate Lindy Lou Isonhood.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...