Administering repurposed drug to treat TB via lungs vs. orally shows promise

November 15, 2016, American Association of Pharmaceutical Scientists
This photomicrograph reveals Mycobacterium tuberculosis bacteria using acid-fast Ziehl-Neelsen stain; Magnified 1000 X. The acid-fast stains depend on the ability of mycobacteria to retain dye when treated with mineral acid or an acid-alcohol solution such as the Ziehl-Neelsen, or the Kinyoun stains that are carbolfuchsin methods specific for M. tuberculosis. Credit: public domain

Tuberculosis (TB) is responsible for more than 1.8 million deaths each year, according to the World Health Organization, yet there has been little significant improvement in therapies in the past 20 years. This chronic disease is systemic, meaning it affects not only the lungs but also other organs, such as the lymph nodes and spleen. But a promising new treatment may be on the horizon.

New research being presented today at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition demonstrates that administering a commonly used to treat TB via the lungs as opposed to oral administration is as effective at a fraction of the dose—estimated up to 10 times less—used in the standard treatment of care. The research also shows this treatment has the potential to reduce toxicity to the body and its organs. The 2016 AAPS Annual Meeting and Exposition is taking place in Denver Nov. 13 - 17.

Pyrazinamide (PZA), a first line agent used in treating TB, is administered orally. PZA is thought to act as a "prodrug," converting to pyrazinoic acid (POA), which is the "active moiety" (the part of a drug that makes the drug work the way it does), by microbial enzymatic action. A significant mechanism of PZA resistance is a mutation of the enzyme associated with the conversion to POA. It has historically been determined that oral POA is not effective against disease, and even recent research has shown limited antituberculosis activity for high oral doses.

Delivery of POA and its hydrolysable ester, n-propyl POA (PAE), can provide the active moiety, mitigating resistance. Given locally to the lungs, it can circumvent oral bioavailability issues and might require less drug to reduce the burden in the lungs, which is a major site of infection and transmission for TB.

"When it comes to TB therapy, there have not been a lot of new drugs introduced to market during the past two decades, and progress is slow despite enormous effort in new drug discovery," said Phillip Durham, a biochemist at RTI International in Raleigh-Durham, N.C.

"What we've done in our research," continued Durham, "is to use a derivative of a drug that has been around for many years—Pyrazinoic acid—and repurposed the drug to deliver it to the lungs, with some very promising results."

The study demonstrated that the aerosol was as effective in the lungs and and outperformed the high dose oral PZA in the spleen. Because oral PZA may have toxic side effects, reducing the dose while providing the same level of efficacy has tremendous potential to benefit patients worldwide.

"For drugs that are not orally bioavailable, the alternative is often injection," said Durham. "Given the dose required, daily therapy, and the physical health of the patients, inhaled therapy has the potential to be far less painful, does not generate biohazardous waste like HIV contaminated needles (HIV/TB coinfection is a problem), and does not need to be kept cold, which is required by many injectables."

Explore further: New nanomedicine approach aims to improve HIV drug therapies

Related Stories

New nanomedicine approach aims to improve HIV drug therapies

October 21, 2016
New research led by the University of Liverpool aims to improve the administration and availability of drug therapies to HIV patients through the use of nanotechnology.

Tuberculosis drug may also target visceral leishmaniasis

May 25, 2016
A drug that has already been approved for treatment of tuberculosis could also be a powerful tool to combat another of the developing world's major diseases, researchers at the University of Dundee have found.

Statins have benefits for asthma sufferers

May 26, 2015
Statins continue to show that their benefits extend beyond their original focus of lowering high cholesterol. With the increasing prevalence of asthma, scientists are studying the effects of statins in the lungs. In a new ...

Development of drugs for local treatment of oral conditions

June 23, 2016
On June 24, 2016, at the 94th General Session & Exhibition of the International Association for Dental Research, researcher W. Peter Holbrook, University of Iceland, will present a study titled "Development of Drugs for Local ...

Recommended for you

A new approach to developing a vaccine against vivax malaria

September 21, 2018
A novel study reports an innovative approach for developing a vaccine against Plasmodium vivax, the most prevalent human malaria parasite outside sub-Saharan Africa. The study led by Hernando A. del Portillo and Carmen Fernandez-Becerra, ...

Pre-clinical success for a universal flu vaccine offers hope for third generation approach

September 21, 2018
Researchers from the University of Oxford's Department of Zoology have demonstrated pre-clinical success for a universal flu vaccine in a new paper published in Nature Communications.

Researchers define possible molecular pathway for neurodegeneration in prion diseases

September 21, 2018
A new study has shed light on the mechanisms underlying the progression of prion diseases and identified a potential target for treatment.

Fighting a deadly parasite: Scientists devise a method to store Cryptosporidium, aiding vaccine research efforts

September 21, 2018
In May, just before one of the hottest summers on record, the U.S. Centers for Disease Control and Prevention issued a warning about diseases lurking in recreational water facilities like swimming pools and water playgrounds. ...

Scientists make significant discovery in the fight against drug-resistant tuberculosis

September 20, 2018
A team of scientists have identified a naturally occurring antibiotic that may help in the fight against drug-resistant Tuberculosis.

Anti-cancer drugs may hold key to overcoming antimalarial drug resistance

September 20, 2018
Scientists have found a way to boost the efficacy of the world's most powerful antimalarial drug with the help of chemotherapy medicines, according to new research published in the journal Nature Communications.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.