Clinical trial marks key milestone in fight against antibiotic resistance

Infections with antibiotic-resistant bacteria cause a significant burden of disease worldwide.
Photo Credit: Scientific Frontline / AI Generated

An international clinical trial, led by The University of Queensland, has been hailed as a significant step forward in the global challenge of antibiotic resistance.

UQ researchers have led the first randomized trial across 6 countries to examine a new antibiotic, cefiderocol, in the treatment of life-threatening, drug-resistant infections.

Associate Professor Patrick Harris, of UQ’s Centre for Clinical Research, said the drug was found to be effective and safe in treating bloodstream infections.

"The study is the first randomized controlled trial to specifically examine the use of cefiderocol in bloodstream infections and sepsis," he said.

“With increasing global antimicrobial resistance, there is a need for the development of new antibiotics.’’

Antibody discovered that blocks almost all known HIV variants in neutralization assays

Image Credit; Scientific Frontline / AI Generated

 A Cologne-led research team has discovered the antibody 04_A06, which neutralizes the human immunodeficiency virus (HIV) in almost all tested variants in vitro and even overcomes typical resistance mechanisms. The discovery potentially opens up new perspectives for the prevention and treatment of HIV infections.

An international research team led by the University of Cologne has discovered an antibody that could advance the fight against HIV. The newly identified antibody 04_A06 proved to be particularly effective in laboratory tests. It was able to neutralize 98.5 percent of more than 300 different HIV strains, making it one of the broadest antibodies against HIV identified. In experiments with humanized mice – animals whose immune system has been modified to resemble that of humans – 04_A06 permanently reduced the HIV viral load to undetectable levels. Most other HIV antibodies, in contrast, only achieve short-term effects in this animal model, as resistance develops quickly. The study ‘Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bNAb for HIV-1 prevention and therapy’ was published in Nature Immunology.

New mechanism revealed: How leukemia cells trick the immune system

Thoas Fioretos, Niklas Landberg, and Carl Sandén are the research team behind the study now being published in Nature Cancer.
Photo Credit: Tove Smeds

A research team at Lund University in Sweden has discovered a mechanism that helps acute myeloid leukemia cells to evade the body’s immune system. By developing an antibody that blocks the mechanism, the researchers could restore the immune system’s ability to kill the cancer cells in laboratory trials and in mice. The discovery is published in Nature Cancer.

Immunotherapy has improved the treatment for many cancers, but progress has been limited in leukemia. Acute myeloid leukemia (AML) is particularly intractable, with a five-year survival rate of just over 30 per cent. The existing treatments are often aggressive and may include both strong chemotherapy and stem cell transplantations.

“We wanted to see if we could find surface proteins unique to leukemia stem cells, and which would therefore act as interesting targets for a targeted treatment. If such proteins were not present on healthy blood stem cells it might be possible to attack the tumor – without harming the healthy blood system,” says Thoas Fioretos, research group leader and professor of clinical genetics at Lund University, and senior consultant at Skåne University Hospital.

Scientists Have Created New Lanthanum Complex Promising for Anti-cancer Therapy

Lanthanum complexes demonstrate antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia.
Photo Credit: Louis Reed

As a result of the joint work of an international group of scientists from Russia (Ural Federal University), Bulgaria (Medical University, Sofia), and Spain (Complutense University of Madrid, Rey Juan Carlos University), a new lanthanum (III) complex with a luminescent triazole ligand has been obtained that is able to selectively regulate the level of reactive oxygen species (ROS) in cells. The result opens up prospects for the development of new anti-cancer and anti-infective drugs. The interim results of the study were published in the journal Molecules.

“New lanthanum complexes demonstrate a wide range of biological effects such as antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia. In a study that we conducted together with biologists from the Medical University of Sofia, we found out that both lanthanum complexes of La(III) and free organic ligands can affect the level of reactive oxygen species. At the same time, we found that they have a dual effect: in some tests, they act as antioxidants, protecting healthy cells, in others, as pro-oxidants, contributing to the death of tumor cells. This specific focus of action makes them promising candidates for the development of new drugs for cancer,” said Natalia Belskaya, Professor at UrFU Department of Technology pf Organic Synthesis.

Potential new therapeutic target for asthma discovered

Photo Credit: Cnordic Nordic

A new way to treat asthma symptoms and even repair previously irreversible lung damage could be on the horizon following the discovery of a potential new therapeutic target by scientists at the Universities of Aberdeen and Manchester.

Current treatments for asthma largely involve controlling the inflammation of lung tissue using steroid inhalers. However, 4 people die every day in the UK from asthma related complications. With funding from the Medical Research Foundation and Asthma UK, a team of researchers from the University of Aberdeen and the University of Manchester have investigated the scarring that occurs in lung tissue as a result of asthma and have been able to reverse these changes in animal models.

Although still in the early stages of development, this discovery paves the way for a new way to treat not only asthma, but many different diseases in which similar structural changes in tissues occur. Such diseases include conditions like chronic obstructive pulmonary disease (COPD), chronic heart disease and cirrhosis of the liver and account for approximately 40% of deaths worldwide.

Asthma affects more than 7 million people in the UK and severe asthma can have a hugely detrimental impact on an individual’s quality of life. Even when treated, asthma can be fatal and the most recent data shows it contributed to 1,465 deaths in the UK in 20221 – this is despite the availability of new treatments which aim to dampen down inflammation in the lungs.

Opening for a new type of drug for Alzheimer’s Disease

Kaj Blennow and Tohidul Islam.
Photo Credit: Johan Wingborg

A complementary drug to combat Alzheimer’s disease could target a specific part of the nerve cell protein tau. This is the finding of research from the University of Gothenburg, which also offers a better way to measure the effect of treatment among patients.

Researchers from the University of Gothenburg, together with colleagues from the University of Pittsburgh in the US, published their findings in the journal Nature Medicine.

The study provides insights into what happens during the earliest phase when the protein tau is transformed into thread-like strands (fibrils) in the nerve cells. This is one of the processes in Alzheimer’s disease and occurs alongside the formation of amyloid plaques. In healthy individuals, the protein tau stabilizes the tubular building blocks (microtubules) that make up the long projections of the nerve cells.

During the development of Alzheimer’s disease, tau undergoes pathological changes. First, tau forms small, soluble aggregates that are secreted from the nerve cells and are thought to be able to spread these changes to other nerve cells. The protein is then converted into larger, harmful, thread-like strands in the nerve cells.

Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
Image Credit: Scientific Frontline stock image

Throughout history, women have made groundbreaking contributions to science, despite facing significant societal barriers and a lack of recognition. Their relentless pursuit of knowledge and innovation has shaped our understanding of the world and paved the way for future generations of scientists. This article celebrates the achievements of some of these remarkable women, highlighting their struggles and the impact of their work.

The women featured in this article, along with countless others throughout history, have made invaluable contributions to the advancement of science. Their achievements, often accomplished in the face of adversity and societal barriers, have shaped our understanding of the world and paved the way for future generations of scientists. These women demonstrate the power of perseverance, the importance of challenging established norms, and the profound impact that individual dedication can have on scientific progress. By recognizing and celebrating their legacies, we not only honor their contributions but also inspire future generations to pursue their passions and break down barriers in the pursuit of knowledge.

WSU researcher pioneers new study model with clues to anti-aging

Jiyue Zhu and a student work in the laboratory.
Photo Credit: Courtesy of Washington State University

Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.

Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.

But research studying these telomeres at the cellular level has been challenging in humans.

Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using genetically engineered mice.

Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.

Powerful anticancer compound might also be the key to eradicating HIV

Study co-authors Jennifer Hamad and Owen McAteer prepare for a cellular assay, a lab technique used to study living cells. The assay will yield information about the location of EBC-46 compounds that have been introduced into cells in the lab.
Photo Credit: Paul Wender

A compound with the unpresuming designation of EBC-46 has made a splash in recent years for its cancer-fighting prowess. Now a new study led by Stanford researchers has revealed that EBC-46 also shows immense potential for eradicating human immunodeficiency virus (HIV) infections. 

Compared to similar-acting agents, EBC-46 excels at activating dormant cells where HIV is hiding, the study found. These “kicked” cells can then be targeted (“killed”) by immunotherapies to fully clear the insidious virus from the body. By pursuing this “kick and kill” strategy with EBC-46, researchers think achieving permanent elimination of HIV in patients—in other words, a cure—is possible.

"We’re pleased to report that EBC-46 performed extremely well in preclinical experiments as part of a ‘kick and kill’ therapeutic," said study senior author Paul Wender, the Bergstrom Professor of Chemistry at Stanford’s School of Humanities and Sciences. "While we still have a lot of work to do before treatments based on EBC-46 might reach the clinic, this study marks unprecedented progress toward the as-yet-unrealized goal of eradicating HIV.” 

Study explains why some osteoporosis drugs may protect against Covid-19

Drugs already in-use for other conditions could help in the fight against Covid-19 and its variants
Photo Credit: Courtesy of University of York

Researchers have provided the molecular explanation for why some osteoporosis drugs offer protection against Covid-19.

Drugs already in-use for other conditions could help in the fight against Covid-19 and its variants

The study, by researchers at the University of York, builds on work conducted by Harvard Medical School that compared more than 450,000 users of a class of drugs, called bisphosphonates, with non-users during the months leading up to the pandemic in 2020. 

The Harvard study showed that those who used drugs, such as alendronate and zoledronate, had lower odds of testing for SARS-CoV-2 infection, Covid-19 diagnosis and Covid-19-related hospitalization, but the study didn’t explain why this was the case.

Researchers develop better way to make painkiller from trees

Steven Karlen, left, and Vitaliy Tymokhin, scientists with the Great Lakes Bioenergy Research Center, examine a reactor used to convert chemicals in poplar trees into paracetamol, the active ingredient in Tylenol.
Photo Credit: Chelsea Mamott

Scientists at the University of Wisconsin–Madison have developed a cost-effective and environmentally sustainable way to make a popular pain reliever and other valuable products from plants instead of petroleum.

Building on a previously patented method for producing paracetamol – the active ingredient in Tylenol – the discovery promises a greener path to one of the world’s most widely used medicines and other chemicals. More importantly, it could provide new revenue streams to make cellulosic biofuels — derived from non-food plant fibers — cost competitive with fossil fuels, the primary driver of climate change.

“We did the R&D to scale it and make it realizable,” says Steven Karlen, a staff scientist at the Great Lakes Bioenergy Research Center who led the research published recently in the journal ChemSusChem.

Paracetamol, also known as acetaminophen, is one of the most widely used pharmaceuticals, with a global market value of about $130 million a year. Since it was introduced in the early 1900s, the drug has traditionally been made from derivatives of coal tar or petroleum.

Drug shows promise for slowing progression of rare, painful genetic disease

A CT angiography scan of a person with ACDC disease showing abnormal calcification of the blood vessels in the legs and feet.
Image Credit: Courtesy of National Institutes of Health

A drug used to treat certain bone diseases shows promise for slowing the progression of a rare, painful genetic condition that causes excessive calcium buildup in the arteries, known as arterial calcification due to deficiency of CD73 (ACDC). These results are from a first-in-human clinical trial supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study, published in the journal Vascular Medicine, could lead to the first effective treatment for the rare disease.

ACDC, which has no known cure, often targets the arteries of the legs and can make walking painful and difficult. It can also affect the joints of the hands, causing pain and deformities. In severe cases, the condition can lead to potential limb loss. Symptoms of the disease often begin in the late teens and 20s. An extremely rare disease, it is believed to affect only about 20 people worldwide and has an estimated prevalence of less than 1 in 1 million. Previous studies have identified the gene for ACDC disease and the biochemical mechanism behind it. More recent studies by the NHLBI research team identified an existing drug, called etidronate, as a potential treatment for ACDC based on disease models in animals and human cells.

Pollen is a promising sustainable tool in the bone regeneration process

Scientists have used pollen to grow hydroxyapatite capsules, so the mineral can better support bone regeneration
Photo Credit: Alex Jones

A study has shown pollen grains can be used as green templates for producing biomaterials, showcasing their potential to support drug delivery and bone regeneration.

With an increasingly ageing population, bone fractures are becoming more common. Bone is generally able to self-repair but if the fracture is too big or the person affected too fragile, as for example people with osteoporosis, the use of bone fillers can help.

Hydroxyapatite (HAp) is an inorganic mineral present in human bone and teeth, which can be used to support bone regeneration. It makes up somewhere between 65 per cent and 70 per cent of the weight of human bone. Healthcare professionals often use synthetic and natural HAp when carrying out bone repair treatments.

A team at the University of Portsmouth has worked with international colleagues to explore sustainable ways to improve the process. 

They examined the feasibility of using pollen grains as bio-templates for growing calcium phosphate minerals in the lab - particularly hydroxyapatite (HAp) and β-tricalcium phosphate (TCP), which are types of calcium phosphate used for bone repair.

Repurposed Cancer Drugs May Improve Tuberculosis Treatment

Mycobacterium tuberculosis bacteria.
Image Credit: NIAID, NIH

Researchers have identified a combination of existing cancer drugs that may improve treatment for tuberculosis.

In a study conducted in rabbits and led by Harvard Medical School researchers at Massachusetts General Hospital, the repurposed drugs enhanced delivery of antibacterial medications that target tuberculosis-causing bacteria.

Although it is often overlooked in industrialized countries such as the United States, tuberculosis remains one of the deadliest diseases globally, causing millions of deaths every year.

Sometimes, patients die even after being treated, either because tuberculosis bacteria develop resistance to antibacterial drugs or because the ability to deliver medications to infected lung tissue is poor.

To address the latter challenge, researchers repurposed a pair of cancer drugs already approved by the U.S. Food and Drug Administration. The drugs were originally designed to enhance drug delivery to cancer cells by improving the structure and function of blood vessels around tumors, which can be compromised in cancer.

Liquid crystal nanoparticles supercharge antibiotics for cystic fibrosis

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Cystic fibrosis is the most common, life-limiting genetic condition in Australia. It affects the lungs, digestive system, and reproductive system, producing excess mucus, infections, and blockages.

Now, thanks to a $500,000 grant from Brandon BioCatalyst's CUREator incubator, through their CSIRO-funded Minimizing Antimicrobial Resistance Stream, University of South Australia researchers are advancing the development of liquid crystal nanoparticle-formulated antibiotics to more accurately target and eliminate difficult-to-cure lung infections in people with cystic fibrosis.

Funded by the Medical Research Future Fund CUREator provides grant funding to support the development of Australian biomedical research and innovations.

The study will use a patent-protected platform technology, invented by UniSA’s Centre for Pharmaceutical Innovation to establish new therapies for cystic fibrosis sufferers. UniSA will also work with the Cystic Fibrosis Airways Research Group at the Women’s and Children’s Hospital to advance the platform.

Researchers a step closer to a cure for HIV

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

A new study involving University of Bristol researchers has shown a virus-like particle (HLP) can effectively 'shock and kill' the latent HIV reservoir.

By 2030, the World Health Organization (WHO), the Global Fund and UNAIDS are hoping to end the human immunodeficiency virus (HIV) and AIDS epidemic. An international team of researchers led by Professor Eric Arts from the Schulich School of Medicine & Dentistry, Canada, and Dr Jamie Mann, Senior Lecturer at the University of Bristol, has brought us another step closer to meeting this goal, by finding an effective and affordable targeted treatment strategy for an HIV cure. 

In a first, the study published in Emerging Microbes and Infections demonstrated the team's patented therapeutic candidate. The HIV-virus-like-particle (HLP), is 100 times more effective than other candidate HIV cure therapeutics for people living with chronic HIV on combined antiretroviral therapy (cART). If successful in clinical trials, HLP could be used by millions of people living around the world to free them of HIV. This study was done using blood samples from people living with chronic HIV. 

HLPs are dead HIV particles hosting a comprehensive set of HIV proteins that increase immune responses without infecting a person. When compared with other potential cure approaches, HLP is an affordable biotherapeutic and can be administered by intramuscular injection – similar to the seasonal flu vaccine. 

New vaccine against a highly fatal tropical disease – and potential bioterror weapon – demonstrates efficacy in animal studies

Burkholderia pseudomallei infecting a human cell. The bacteria (red) are polymerizing actin (green).
 Photo Credit: Courtesy of Christopher T. French.

In a mouse study, UCLA researchers tested a vaccine against the bacterium that causes melioidosis and found it was highly protective against the disease, which is endemic in many tropical areas, causing approximately 165,000 cases with 89,000 fatalities around the world each year. 

The bacterium, called Burkholderia pseudomallei, is spread through contact with contaminated soil and water through inhalation, ingestion or broken skin. It is so dangerous that it is categorized as a Tier 1 Select Agent of bioterrorism, and it can cause rapidly fatal pneumonia when inhaled in low doses. If aerosolized and unleashed in a terror attack, it could lead to widespread death.

To date there are no licensed vaccines against the bacterium, said senior author Dr. Marcus Horwitz, Distinguished Professor of Medicine, in the division of infectious diseases, and of Microbiology, Immunology and Molecular Genetics at the David Geffen School of Medicine at UCLA.

“A safe and effective vaccine is needed to prevent this disease as melioidosis is often difficult to diagnose, requires very lengthy treatment lasting three to six months, and has a high fatality rate even in high resource settings,” Horwitz said. “Such a vaccine would be of great benefit to people living in endemic regions, travelers, and military personnel stationed in these areas, and it would also reduce the risk from an intentional release of B. pseudomallei in a bioterrorist attack.” 

Adding ribociclib to hormone therapy reduces the risk of breast cancer recurrence

Photo Credit: National Cancer Institute

A new treatment approach that combines a targeted therapy drug with hormone therapy significantly increased the amount of time a person with stage 2 or 3 HR-positive, HER2-negative early breast cancer lives without the cancer returning, according to a new study co-led by UCLA Health Jonsson Comprehensive Cancer Center investigators.

The team found adding ribociclib, a drug that belongs to a class of CDK4/6 inhibitors, to standard hormone therapy not only improved invasive-free survival in women with this type of early-stage breast cancer, but also improves distant disease-free survival and recurrence-free survival.

The results were published today in the New England Journal of Medicine and findings were presented last year at the American Society of Clinical Oncology Annual Meeting in Chicago.

“We found that adding ribociclib to the standard hormone therapy resulted in a relative reduction in the recurrence rate by as much as 25%,” said first author of the study Dr. Dennis Slamon, chair of hematology-oncology at the David Geffen School of Medicine at UCLA and director of clinical and translational research at the UCLA Health Jonsson Comprehensive Cancer Center. “And that’s huge for this the group of patients, who make up 70% to 75% of breast cancer cases.”

Many patients with this type of breast cancer are treated with surgery, and in some cases with radiation and chemotherapy, followed by endocrine therapy for up to 10 years to help reduce their risk of recurrence.

Alzheimer’s Drug Fermented with Help from AI and Bacteria Moves Closer to Reality

Photo-Illustration Credit: Martha Morales/The University of Texas at Austin

Galantamine is a common medication used by people with Alzheimer’s disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn’t commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug. 

Now, researchers at The University of Texas at Austin have developed tools — including an artificial intelligence system and glowing biosensors — to harness microbes one day to do all the work instead. 

In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe’s normal cellular metabolism.  Essentially, the bacteria are programmed to convert food into medicinal compounds.

“The goal is to eventually ferment medicines like this in large quantities,” said Andrew Ellington, a professor of molecular biosciences and author of the study. “This method creates a reliable supply that is much less expensive to produce. It doesn’t have a growing season, and it can’t be impacted by drought or floods.” 

“Molecular Rosetta Stone” Reveals How our Microbiome Talks to Us

Bacteria in the gut convert bile acids produced by the liver into a wide array of new compounds. These molecules are akin to the language of the gut microbiome, allowing them to influence distant organ systems.
Photo Credit: Lakshmiraman Oza

Researchers from Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have uncovered thousands of previously unknown bile acids, a type of molecule used by our gut microbiome to communicate with the rest of the body.

“Bile acids are a key component of the language of the gut microbiome, and finding this many new types radically expands our vocabulary for understanding what our gut microbes do and how they do it,” said senior author Pieter Dorrestein, Ph.D., professor at Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of pharmacology and pediatrics at UC San Diego School of Medicine. “It’s like going from ‘See Spot Run’ to Shakespeare.”

The results, as described by study co-author and bile acids expert Lee Hagey, Ph.D, are akin to a molecular Rosetta stone, providing previously unknown insight into the biochemical language microbes use to influence distant organ systems.