Medical

Stalled Alzheimer's drug may find new purpose against superbugs

Stalled Alzheimer's drug may f...
Researchers have repurposed an experimental Alzheimer's drug to fight antibiotic-resistant bacteria
Researchers have repurposed an experimental Alzheimer's drug to fight antibiotic-resistant bacteria
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Researchers have repurposed an experimental Alzheimer's drug to fight antibiotic-resistant bacteria
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Researchers have repurposed an experimental Alzheimer's drug to fight antibiotic-resistant bacteria
Pairing the antibiotic ampicillin with the molecule PBT2 worked much better to clear out infection of drug-resistant bacteria in the lungs of mice, compared to ampicillin alone
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Pairing the antibiotic ampicillin with the molecule PBT2 worked much better to clear out infection of drug-resistant bacteria in the lungs of mice, compared to ampicillin alone

Our antibiotics are failing in large numbers, threatening a future “dark age of medicine” where once-simple infections become lethal again. A team of scientists has now found a way to restore common antibiotics to their former strength, by repurposing a molecule developed to treat Alzheimer’s.

Antibiotics were one of the most important scientific achievements of the 20th century, but unfortunately their effectiveness is running out. Bacteria have been steadily evolving resistance to the drugs over decades, to the point that we’re beginning to run out of effective antibiotics.

New drugs are regularly in development, but the so-called superbugs are outpacing us, forcing scientists to come up with more creative solutions. One of the most promising avenues of research is in finding ways to make old drugs effective again, by making modifications to them or pairing them with things like blue light, gold nanoclusters, bacteriophages, probiotics, various molecules and peptides, or existing drugs designed for other diseases.

The breakthrough in the new study comes from that last group. PBT2 is an experimental drug candidate developed to treat diseases like Alzheimer’s and Huntington’s, but clinical trials proved disappointing. However, it may get a new lease on life in the war against superbugs, with the team taking advantage of the fact that PBT2 increases zinc concentrations.

“We knew from earlier research that the immune system uses zinc as an innate antimicrobial to fight off infection,” says Professor Christopher McDevitt, lead researcher on the study. “So, we developed our therapeutic approach with PBT2 to use the body’s antimicrobial zinc to break antibiotic resistance in the invading bacteria.”

Pairing the antibiotic ampicillin with the molecule PBT2 worked much better to clear out infection of drug-resistant bacteria in the lungs of mice, compared to ampicillin alone
Pairing the antibiotic ampicillin with the molecule PBT2 worked much better to clear out infection of drug-resistant bacteria in the lungs of mice, compared to ampicillin alone

The team tested the molecule against drug-resistant strains of the common bacteria Streptococcus pneumoniae, and found that it rendered the bugs sensitive to a range of antibiotics once again. Follow-up experiments were conducted on mice with pneumonia, caused by a strain of the same bacteria that was resistant to the antibiotic ampicillin. Mice treated with ampicillin alone saw little change, but the infection was cleared out for mice treated with ampicillin and PBT2 together.

While PBT2 may not have performed well against Alzheimer’s, the clinical trials at least showed that it was safe for use in humans, which the team says is a good step. Further study will need to be conducted to prepare PBT2 for trials in humans as a potential superbug treatment.

The research was published in the journal Cell Reports.

Source: University of Melbourne

2 comments
2 comments
bothib
I have no medical background at all but I think this could be one of the most important discoveries in this decade.
Karmudjun
Nice article Michael. The last paragraph understated the hurdles ahead for any human therapy regimens in the near future. While the mechanism of action has been analyzed and it appears to be a useful adjunct to break the cycle of antibiotic resistance to beta-lactam antibiotics, there still remains quite a bit of research to be conducted with multiple staged trials before we can utilize this outside of experimental therapy. The good news is PBT2 appears safe in humans at the intended Alzheimer's dosages and it appears to be helpful with standard antibotic dosages - ie., it MAY not make the antibiotic dosage too high for a human to tolerate - but research remains!

And what might the marketable price for the adjunctive therapy be? No word - but certainly there must be some recruitment of developmental costs and FDA trials for this failed moleculer therapeutic.