Australian researchers aim to rescue common antibiotics with a new therapeutic approach, using a drug originally developed to treat neurodegenerative disorders
(BOSTON: October 3, 2023) – Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is awarding US$1.75 million to the University of Melbourne at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) to develop an oral therapeutic that restores the activity of workhorse antibiotics used to treat community-acquired bacterial pneumonia (CABP).
Lower respiratory tract infections, including CABP, are among the world’s most deadly communicable diseases. They are estimated to have killed 2.6 million people in 2019 globally, and they cause a substantial mortality, morbidity and economic burden for vulnerable people in low-income countries, where they are the second leading cause of death. Patients with CABP struggle to breathe as their lungs fill with fluid, and they can require hospitalization and intensive care treatment.
“Bacteria that cause community-acquired pneumonia are becoming increasingly resistant to antibiotics on the WHO model list of essential medicines, and so we’ve taken a strategy that embraces both the development of new antibiotics and the pursuit of other products that aim to restore the utility of the ones we already have,” said Erin Duffy, PhD, R&D Chief of CARB-X. “Oral antibiotics enable patients to be treated at home, which can reduce healthcare costs and increase access globally, including in low- and middle-income countries where the burden of antimicrobial resistance is highest.”
More than 400,000 people globally died in 2019 due to lower respiratory tract infections attributable to drug-resistant bacteria, and even in a high-income country like the US, 22% of CABP cases result in treatment failure due to antibiotic resistance.
The CARB-X award supports the development of PBT2, an ionophore therapeutic originally pursued as a potential treatment to restore brain activity in patients with neurodegenerative disorders, including Alzheimer’s and Huntington’s diseases. Studies found that PBT2 is also able to disarm key pathways involved in mechanisms by which bacteria become resistant to frontline antibiotics, like amoxicillin and doxycycline. The Australian research team, led by Professor Christopher McDevitt, PhD, Laboratory Head at the Doherty Institute, aims to use the effects of PBT2 on drug-resistant bacteria to restore the ability of common antibiotics to effectively eliminate those bacteria.
University of Melbourne Laureate Professor Sharon Lewin, MD, PhD, Director of the Doherty Institute, said that CARB-X’s generous support to take this research from lab benches to market is an important milestone. “We’re grateful for CARB-X’s support, providing an accelerated pathway for the development of this new therapeutic to render these drug-resistant bacteria susceptible to existing antibiotics again,” said Lewin. “As a multidisciplinary research institute specializing in infection and immunity, our vision is to improve health globally, and collaborating with like-minded organisations–like CARB-X and their global network of subject matter experts–is crucial to make it happen.”
An estimated 1.27 million people died due to drug-resistant bacterial infections in 2019, a death toll that exceeded HIV/AIDS (864,000) and malaria (643,000) in that same year. CARB-X is building a pipeline of high-value products to prevent, diagnose and treat bacterial infections, including those that have become resistant to antibiotics. CARB-X emphasizes performance characteristics that will allow the broadest use of these products against infections driving the greatest global morbidity and mortality.
When CARB-X was founded in 2016, the early-stage antibiotic pipeline was stalled. Since then, CARB-X has supported 92 R&D projects in 12 countries, and CARB-X product developers have made tremendous progress: 18 projects have advanced into or completed clinical trials; 12 remain active in clinical development, including late-stage clinical trials; and two diagnostic products have reached the market. Additionally, at least 9 product developers with active R&D projects have already secured advanced development partnerships which can help support their clinical development after leaving the CARB-X portfolio.
Last year, CARB-X launched new funding rounds to support R&D projects and fill critical gaps in the antibacterial pipeline. These include oral therapeutics to replace the workhorse antibiotics that are failing; vaccines for neonatal sepsis, which kills 2.5 million infants annually; and oral therapeutics, vaccines and rapid diagnostics for gonorrhea. Resistant strains of gonorrhea have evaded all but one existing antibiotic. The University of Melbourne’s PBT2 oral therapeutic is the first project to receive a CARB-X grant as part of the 2022-2023 funding call. Additional projects are under review, and new product developers will be announced this year.
CARB-X funding for this research is supported by federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; under Agreement number: 75A50122C00028, and by awards from Wellcome (WT224842), Germany’s Federal Ministry of Education and Research (BMBF), the UK Global Antimicrobial Resistance Innovation Fund (GAMRIF) funded by the UK Government Department of Health and Social Care (DHSC), and the Bill & Melinda Gates Foundation. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of any CARB-X funders.
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The Peter Doherty Institute for Infection and Immunity at the University of Melbourne Contact:
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CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) is a global non-profit partnership dedicated to supporting early-stage antibacterial research and development to address the rising threat of drug-resistant bacteria. CARB-X supports innovative therapeutics, preventatives and rapid diagnostics. CARB-X is led by Boston University and funded by a consortium of governments and foundations. CARB-X funds only projects that target drug-resistant bacteria highlighted on the CDC’s Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO, with a priority on those pathogens deemed Serious or Urgent on the CDC list or Critical or High on the WHO list. https://carb-x.org/ | Twitter @CARB_X
About the Peter Doherty Institute for Infection and Immunity at the University of Melbourne
Finding solutions to prevent, treat, and cure infectious diseases and understanding the complexities of the immune system requires innovative approaches and concentrated effort. This is why the University of Melbourne – a world leader in education, teaching and research excellence – and the Royal Melbourne Hospital – an internationally renowned institution providing outstanding care, treatment and medical research – have partnered to create the Peter Doherty Institute for Infection and Immunity (Doherty Institute); a centre of excellence where leading scientists and clinicians collaborate to improve human health globally. https://www.doherty.edu.au/ | Twitter @TheDohertyInst
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Founded in 1839, Boston University is an internationally recognized institution of higher education and research. With nearly 37,000 students, it is the third-largest independent university in the United States. BU consists of 17 schools and colleges and the interdisciplinary Faculty of Computing & Data Sciences, along with a number of multi-disciplinary centers and institutes integral to the University’s research and teaching mission. In 2012, BU joined the Association of American Universities (AAU), a consortium of 65 leading research universities in the United States and Canada. For further information, please contact Kim Miragliuolo at firstname.lastname@example.org. www.bu.edu