Nav: Home

How an AI solution can design new tuberculosis drug regimens

November 21, 2019

ANN ARBOR--With a shortage of new tuberculosis drugs in the pipeline, a software tool from the University of Michigan can predict how current drugs--including unlikely candidates--can be combined in new ways to create more effective treatments.

"This could replace our traditional trial-and-error system for drug development that is comparatively slow and expensive," said Sriram Chandrasekaran, U-M assistant professor of biomedical engineering, who leads the research.

Dubbed INDIGO, short for INferring Drug Interactions using chemoGenomics and Orthology, the software tool has shown that the potency of tuberculosis drugs can be amplified when they are teamed with antipsychotics or antimalarials.

"This tool can accurately predict the activity of drug combinations, including synergy--where the activity of the combination is greater than the sum of the individual drugs," said Shuyi Ma, a research scientist at the University of Washington and a first author of the study. "It also accurately predicts antagonism between drugs, where the activity of the combination is lesser. In addition, it also identifies the genes that control these drug responses."

Among the combinations INDIGO identified as showing a strong likelihood of effectiveness against tuberculosis were:

A five-drug combination of tuberculosis drugs Bedaquiline, Clofazimine, Rifampicin, Clarithromycin with the antimalarial drug P218. A four-drug combination of Bedaquiline, Clofazimine, Pretomanid and the antipsychotic drug Thioridazine. A combination of antibiotics Moxifloxacin, Spectinomycin--two drugs that are typically antagonistic but can be made highly synergistic by the addition of a third drug, Clofazimine.

All three groupings were in the top .01% of synergistic combinations identified by INDIGO.

"Successful combinations identified by INDIGO, when tested in a lab setting, showed synergy 88.8% of the time," Chandrasekaran said.

Tuberculosis kills 1.8 million people each year and is the world's deadliest bacterial infection. There are 28 drugs currently used to treat tuberculosis, and those can be combined into 24,000 three- or four-drug combinations. If a pair of new drugs is added to the mix, that increases potential combinations to 32,000.

These numbers make developing new treatment regimens time-consuming and expensive, the researchers say. At the same time, multidrug resistant strains are rapidly spreading.

At a time when new drugs are in short supply to deal with old-but-evolving diseases, this tool presents a new way to utilize medicine's current toolbox, they say. Answers may already be out there, and INDIGO's outside-the-box approach represents a faster way of finding them.

INDIGO utilizes a database of previously published research, broken down and quantified by the authors, along with detailed information on the properties of hundreds of drugs.
-end-
The team's research results appear in mBio. The work was supported by the National Institutes of Health and the U-M Precision Health and MCubed initiatives.

Study: Transcriptomic Signatures Predict Regulators of Drug Synergy and Clinical Regimen Efficacy against Tuberculosis

Systems Biology LabAdditional contact: Jim Lynch, 313-727-5045, lynchja@umich.edu

University of Michigan

Related Tuberculosis Articles:

Blocking the iron transport could stop tuberculosis
The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply.
Tuberculosis: New insights into the pathogen
Researchers at the University of Würzburg and the Spanish Cancer Research Centre have gained new insights into the pathogen that causes tuberculosis.
Unmasking the hidden burden of tuberculosis in Mozambique
The real burden of tuberculosis is probably higher than estimated, according to a study on samples from autopsies performed in a Mozambican hospital.
HIV/tuberculosis co-infection: Tunneling towards better diagnosis
1.2 million people in the world are co-infected by the bacteria which causes tuberculosis and AIDS.
Reducing the burden of tuberculosis treatment
A research team led by MIT has developed a device that can lodge in the stomach and deliver antibiotics to treat tuberculosis, which they hope will make it easier to cure more patients and reduce health care costs.
Tuberculosis: Commandeering a bacterial 'suicide' mechanism
The bacteria responsible for tuberculosis can be killed by a toxin they produce unless it is neutralized by an antidote protein.
A copper bullet for tuberculosis
Tuberculosis is a sneaky disease, and the number one cause of death from infectious disease worldwide.
How damaging immune cells develop during tuberculosis
Insights into how harmful white blood cells form during tuberculosis infection point to novel targets for pharmacological interventions, according to a study published in the open-access journal PLOS Pathogens by Valentina Guerrini and Maria Laura Gennaro of Rutgers New Jersey Medical School, and colleagues.
How many people die from tuberculosis every year?
The estimates for global tuberculosis deaths by the World Health Organisation (WHO) and the Institute for Health Metrics and Evaluation (IHME) differ considerably for a dozen countries, according to a study led by ISGlobal.
Beyond killing tuberculosis
Historically, our view of host defense against infection was that we must eliminate pathogens to eradicate disease.
More Tuberculosis News and Tuberculosis Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.