New tuberculosis treatment is inhalable
Researchers have developed a new inhalable form of tuberculosis treatment that could significantly reduce the burden of current therapy.
The study’s findings appear in the journal Antimicrobial Agents and Chemotherapy.
Jessica L. Reynolds, associate professor of medicine in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, is senior author on the paper.
The paper details the development of an inhalable, immunomodulating, biocompatible nanoparticle system encapsulating rifampin, one of the most important tuberculosis (TB) drugs.
“TB is still one of the world’s deadliest infectious diseases, even though it can be cured. Treatment takes many months and involves multiple drugs that can cause serious side effects,” Reynolds says. “Because of this, many patients struggle to finish treatment, which leads to treatment failure and drug-resistant TB.”
Rifampin works well but has two major drawbacks when taken orally: It can damage the liver and not enough of the drug reaches the lungs, where TB bacteria live, Reynolds notes.
To address this, the researchers developed a new way to deliver rifampin directly to the lungs by inhalation instead of pills by packaging the drug into nanoparticles designed to be breathed in.
The nanoparticles have a biodegradable core that holds rifampin, an outer coating that helps them stick to macrophages and a natural molecule on the surface that both improves uptake by immune cells and boosts immune activity, says Hilliard L. Kutscher, research assistant professor of medicine, and first author on the study.
“These particles are specially built to go straight to the lungs and be taken up by lung immune cells called macrophages, which are where TB bacteria hide,” he adds.
“They are designed to slowly release rifampin over time, to stimulate the immune system to better fight TB and to reduce drug exposure to the rest of the body, lowering side effects.”
Because the drug stays in the lungs longer using this form of delivery, treatment might only be needed once a week instead of every day, Kutscher suggests.
In the study, the researchers used two different mouse models of TB (one that reflects general TB lung infection, and a second, more severe model that closely mimics human TB lung damage and is harder to treat) to test whether once-weekly inhaled nanoparticles work as well as—or better than—daily oral rifampin in reducing mycobacterium tuberculosis.
“Using both models makes the results more reliable and relevant to human disease,” Reynolds says.
The study found that inhaled nanoparticle treatment delivered rifampin much more effectively to the lungs.
“Compared to taking rifampin by mouth every day, the inhaled nanoparticles kept higher levels of the drug in the lungs for much longer—up to a week after a single dose,” Reynolds notes.
All studies involving Mycobacterium tuberculosis were conducted in a certified Biosafety Level 3 (BSL-3) facility, the standard laboratory environment required for TB research nationwide. These facilities operate under established federal, state and institutional regulations and include controlled access, specialized ventilation, sterilization and other validated safety procedures.
“The work highlights the potential of long-acting inhaled medicines to simplify TB therapy,” Reynolds says.
“Reducing treatment frequency could improve adherence, lower side effects and make TB care more accessible worldwide,” she says.
“These findings support continued development of inhalable, long-acting TB therapies as a promising strategy to improve treatment outcomes and reduce the global impact of tuberculosis.”
She adds that the next phase of this research will focus on how the nanoparticle can be integrated with other standard TB antibiotics to support combination therapy, the cornerstone of TB treatment.
Patrick O. Kenney, clinical assistant professor of pediatrics and coauthor on the study, says the potential public health benefits of the research go beyond tuberculosis.
“Rifampin is not just a TB drug; it is also a key medication for other serious lung infections caused by non-tuberculous mycobacteria, such as Mycobacterium kansasii and Mycobacterium xenopi, which are increasingly recognized in the US,” Kenney says.
“These infections often affect people with chronic lung disease and can be difficult to treat.”
Kenney says targeted lung delivery could also potentially solve a long-standing drug interaction problem.
“One major limitation of rifampin is that when taken orally, it strongly activates liver enzymes and this reduces the effectiveness of other important antibiotics, such as azithromycin and clarithromycin, which are cornerstones of therapy for Mycobacterium avium/intracellulare complex (MAC) lung disease,” he says. “Because of this interaction, rifampin is often avoided, even when it could otherwise help.”
However, by delivering rifampin directly to the lungs instead of the whole body, this approach could achieve high drug levels at the site of the infection, minimize drug levels in the bloodstream and potentially reduce harmful drug-drug interactions, Kenney notes.
“That opens the door to using rifampin more effectively in a broader range of pulmonary mycobacterial diseases—not just TB,” he says.
The research was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Source: University at Buffalo
The post New tuberculosis treatment is inhalable appeared first on Futurity.
Apes can imagine things like humans do
In a series of tea party-like experiments, researchers demonstrated for the first time that apes can use their imagination and play pretend, an ability thought to be uniquely human.
Consistently and robustly across three experiments, one bonobo engaged with cups of imaginary juice and bowls of pretend grapes, challenging long-held assumptions about the abilities of animals.
“It really is game-changing that their mental lives go beyond the here and now.”
The findings suggest that the capacity to understand pretend objects is within the cognitive potential of, at least, an enculturated ape, and likely dates back 6 to 9 million years, to our common evolutionary ancestors.
“It really is game-changing that their mental lives go beyond the here and now,” says co-author Christopher Krupenye, a Johns Hopkins University assistant professor in the psychological and brain sciences department who studies how animals think.
“Imagination has long been seen as a critical element of what it is to be human, but the idea that it may not be exclusive to our species is really transformative.
“Jane Goodall discovered that chimps make tools, and that led to a change in the definition of what it means to be human. And this, too, really invites us to reconsider what makes us special and what mental life is out there among other creatures.”
The findings are published today in Science.
By age 2, human children can engage in pretend scenarios, like tea parties. Even at 15-months-old, infants show measures of surprise when they see a person “drinking” from a cup after pretending to empty it.
There had been no controlled studies of pretense in nonhuman animals, despite several anecdotal reports of animals seemingly engaging in pretending behavior from both the wild and captivity.
For example, in the wild, young female chimpanzees have been observed carrying and playing with sticks, holding them like mothers would hold their infants. And a chimpanzee in captivity seemed to drag imaginary blocks along the floor after playing with real wooden blocks.
Krupenye and coauthor Amalia Bastos, a former Johns Hopkins postdoctoral fellow who is now a lecturer at Scotland’s University of St. Andrews, wondered if they could test this capacity to pretend in a controlled environment.
They created experiments very similar to a child’s tea party to test Kanzi, a 43-year-old bonobo living at Ape Initiative, who had been anecdotally reported to engage in pretense and could respond to verbal prompts by pointing.
In each test, an experimenter and Kanzi faced one another, tea party-style, across a table set with either empty pitchers and cups or bowls and jars.
In the first task there were two transparent cups on the table, both empty, alongside an empty transparent pitcher. The experimenter tipped the pitcher to “pour” a little pretend juice into each cup, then pretended to dump the juice out of one cup, shaking it a bit to really get it out. They then asked Kanzi, “Where’s the juice?”
Kanzi pointed to the correct cup that still contained pretend juice most of the time, even when the experimenter changed the location of the cup filled with pretend juice.
In case Kanzi thought there was real juice in the cup, even if he couldn’t see it, the team ran a second experiment. This time there was a cup of real juice alongside the cup of pretend juice. When Kanzi was asked what he wanted, he pointed toward the real juice almost every time.
A third experiment repeated the same concept, except with grapes. An experimenter pretended to sample a grape from an empty container, then placed it inside one of the two jars. They pretended to empty one of the containers and asked Kanzi, “Where’s the grape?” Kanzi again indicated the location of the pretend object.
Kanzi was never perfect, but he was consistently correct.
“It’s extremely striking and very exciting that the data seem to suggest that apes, in their minds, can conceive of things that are not there,” Bastos says.
“Kanzi is able to generate an idea of this pretend object and at the same time know it’s not real.”
The findings inspire continued study, especially trying to test whether other apes and other animals can engage in pretend play or track pretend objects. The team also hopes to explore other facets of imagination in apes, perhaps their ability to think about the future or to think about what’s going on in the minds of others.
“Imagination is one of those things that in humans gives us a rich mental life. And if some roots of imagination are shared with apes, that should make people question their assumption that other animals are just living robotic lifestyles constrained to the present,” Krupenye says.
“We should be compelled by these findings to care for these creatures with rich and beautiful minds and ensure they continue to exist.”
Support for the work came from the Johns Hopkins Provost’s Postdoctoral Fellowship Program, Templeton World Charity Foundation, CIFAR Azrieli Global Scholars, and an Early Career Collaboration Enhancement Award from the Diverse Intelligences Summer Institute.
Source: Johns Hopkins University
The post Apes can imagine things like humans do appeared first on Futurity.