Repurposing existing drugs to fight new COVID-19 variants

Photo Credit: Myriam Zilles

MSU researchers are using big data and AI to identify current drugs that could be applied to treat new COVID-19 variants

Finding new ways to treat the novel coronavirus and its ever-changing variants has been a challenge for researchers, especially when the traditional drug development and discovery process can take years. A Michigan State University researcher and his team are taking a hi-tech approach to determine whether drugs already on the market can pull double duty in treating new COVID variants.

“The COVID-19 virus is a challenge because it continues to evolve,” said Bin Chen, an associate professor in the College of Human Medicine. “By using artificial intelligence and really large data sets, we can repurpose old drugs for new uses.”

Chen built an international team of researchers with expertise on topics ranging from biology to computer science to tackle this challenge. First, Chen and his team turned to publicly available databases to mine for the unique coronavirus gene expression signatures from 1,700 host transcriptomic profiles that came from patient tissues, cell cultures and mouse models. These signatures revealed the biology shared by COVID-19 and its variants.

How the secrets of the ‘water bear’ could improve lifesaving drugs like insulin

A tardigrade, or water bear, floating in water. The tiny organism can endure some of the most extreme conditions on Earth — and even space.
Credit: Schokraie E, Warnken U, Hotz-Wagenblatt A, Grohme MA, Hengherr S, et al. licensed under the Creative Commons Attribution 2.5 Generic license.

UCLA chemist Heather Maynard had to wonder: How do organisms like the tardigrade do it?

This stocky microscopic animal, also known as a water bear, can survive in environments where survival seems impossible. Tardigrades have been shown to endure extremes of heat, cold and pressure — and even the vacuum of space — by entering a state of suspended animation and revitalizing, sometimes decades later, under more hospitable conditions. 

If she could understand the mechanism behind this extraordinary preservation, Maynard reckoned, she might be able to use the knowledge to improve medicines so that they remain potent longer and are less vulnerable to typical environmental challenges, ultimately broadening access and benefiting human health.

It turns out that one of the processes protecting tardigrades is spurred by a sugar molecule called trehalose, commonly found in living things from plants to microbes to insects, some of which use it as blood sugar. For a few select organisms, such as the water bear and the spiky resurrection plant, that can revive after years of near-zero metabolism and complete dehydration, trehalose’s stabilizing power is the secret to their unearthly fortitude.

A potential new treatment for brain tumors

Featured photo at top of Pankaj Desai, left, and senior graduate research assistant Aniruddha Karve, right, in the lab.
Photo credit: Andrew Higley | University of Cincinnati

A research question posed in Pankaj Desai’s lab has led to a decade of research, a clinical trial and major national funding to further investigate a potential new treatment for the deadliest form of brain tumors.

Desai, PhD, and his team at the University of Cincinnati recently received a $1.19 million grant from the National Institutes of Health/National Institute of Neurological Disorders and Stroke to continue research into the use of a drug called letrozole to treat glioblastomas (GBM).

Research progression

GBMs are aggressive brain tumors that patients often are unaware of until symptoms emerge and the tumor is substantial. Current treatments include immediate surgery to safely remove as much tumor as possible, radiation and chemotherapy, but the tumor often recurs or becomes resistant to treatments. The average patient survives no more than 15 months after diagnosis.

The medication letrozole was approved by the U.S. Food and Drug Administration as a treatment for postmenopausal women with breast cancer in 2001. The drug works by targeting an enzyme called aromatase that is present in breast cancer cells and helps the cancer grow.

Fighting fungal infections with metals

A Petri dish with red agar on which grows a fungal strand in the shape of the element symbol for platinum (Pt).
Credit: CO-ADD

An international collaboration led by researchers from the University of Bern and the University of Queensland in Australia has demonstrated that chemical compounds containing special metals are highly effective in fighting dangerous fungal infections. These results could be used to develop innovative drugs which are effective against resistant bacteria and fungi.

Each year, more than one billion people contract a fungal infection. Although they are harmless to most people, over 1.5 million patients die each year as a result of infections of this kind. While more and more fungal strains are being detected that are resistant to one or more of the available drugs, the development of new drugs has come to a virtual standstill in recent years. Today, only around a dozen clinical trials are underway with new active agents for the treatment of fungal infections. “In comparison with more than a thousand cancer drugs that are currently being tested on human subjects, this is an exceptionally small number,” explains Dr. Angelo Frei of the Department of Chemistry, Biochemistry and Pharmacy at the University of Bern, lead author of the study. The results have been published in the journal JACS Au.

Boosting antibiotics research with crowd sourcing

The CO-ADD Team at work in the laboratory.
Credit: CO-ADD

To encourage the development of anti-fungal and antibacterial agents, researchers at the University of Queensland in Australia have founded the Community for Open Antimicrobial Drug Discovery, or CO-ADD. The ambitious goal of the initiative is to find new antimicrobial active agents by offering chemists worldwide the opportunity to test any chemical compound against bacteria and fungi at no cost. As Frei explains, the initial focus of CO-ADD has been on “organic” molecules, which mainly consist of the elements of carbon, hydrogen, oxygen and nitrogen, and do not contain any metals.

However, Frei, who is trying to develop new metal-based antibiotics with his research group at the University of Bern, has found that over 1,000 of the more than 300,000 compounds tested by CO-ADD contained metals. “For most folks, when used in connection with the word ‘people’, the word metal triggers a feeling of unease. The opinion that metals are fundamentally harmful to us is widespread. However, this is only partially true. The decisive factor is which metal is used and in which form,” explains Frei, who is responsible for all the metal compounds in the CO-ADD database.

Low toxicity demonstrated

Dr. Angelo Frei at work in the laboratory.
Credit: Angelo Frei

In their new study, the researchers turned their attention to the metal compounds which showed activity against fungal infections. Here, 21 highly-active metal compounds were tested against various resistant fungal strains. These contained the metals cobalt, nickel, rhodium, palladium, silver, europium, iridium, platinum, molybdenum and gold. “Many of the metal compounds demonstrated a good activity against all fungal strains and were up to 30,000 times more active against fungi than against human cells,” explains Frei. The most active compounds were then tested in a model organism, the larvae of the wax moth. The researchers observed that just one of the eleven tested metal compounds showed signs of toxicity, while the others were well tolerated by the larvae. In the next step, some metal compounds were tested in an infection model, and one compound was effective in reducing the fungal infection in larvae.

Considerable potential for broad application

Metal compounds are not new to the world of medicine: Cisplatin, for example, which contains platinum, is one of the most widely used anti-cancer drugs. Despite this, there is a long way to go before new antimicrobial drugs that contain metals can be approved. “Our hope is that our work will improve the reputation of metals in medical applications and motivate other research groups to further explore this large but relatively unexplored field,” says Frei. “If we exploit the full potential of the periodic table, we may be able to prevent a future where we don’t have any effective antibiotics and active agents to prevent and treat fungal infections.”

The study was supported by the Swiss National Science Foundation, the Wellcome Trust and the University of Queensland, among others.

Source/Credit: University of Bern

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Brain Injury Model Created to Find New Medication

The experiments on the fish were conducted non-invasively, using a laser machine.
Photo credit: Danil Lomovskikh

Scientists from Russia and Taiwan (China) have developed and successfully tested a new model of traumatic brain injury (TBI) in zebradanio fish (Danio rerio). The method is based on irradiating the brains of adult individuals of these popular aquarium and laboratory fish with a unique laser system with precise aiming, which was specially developed by scientists. The application of this model allowed the researchers to simulate the TBI and identify molecular targets promising for the treatment of neurotrauma and its consequences. This paves the way for preclinical zebrafish testing of new neuroprotective medications.

The work was financially supported by the Russian Science Foundation (grant № 20-65-46006). An article describing the research was published in the highly rated scientific journal Pharmaceutics. The subject of the research was explained by Alan Kaluev, professor of the Russian Academy of Sciences, member of the European Academy, leading researcher of the Research Institute of Neuroscience and Medicine, professor of the St. Petersburg State University and Sirius Scientific-Technological University, leading researchers of the Ural Federal University and the Moscow Institute of Physics and Technology. Professor Kaluev is a leading scientist within the framework of research conducted at the Scientific Novosibirsk Research Institute of Neuroscience and Medicine (laboratory of Tamara Amstislavskaya and Maria Tikhonova).

The most common experimental models of brain injury in both rodents and zebrafish, such as mechanical blows to the head or needle piercing of the brain, involve penetrating brain tissue damage. However, these models do not correctly reproduce TBI. In the created model, due to the fact that the skin and skull of the used zebradanio species are transparent, it was possible to hit directly the brain, and non-invasively.

‘Drug factory’ implants eliminate mesothelioma tumors in mice

Tiny alginate bead implants invented in the laboratory of Rice University bioengineer Omid Veiseh can be loaded with cells that produce cytokine, proteins that play a major role in immune response. A new study found a treatment combining the implants and checkpoint inhibitor drugs eradicated advanced mesothelioma tumors in all seven mice in which it was tested.
Photo credit: Jeff Fitlow/Rice University

Rice University and Baylor College of Medicine researchers have shown they can eradicate advanced-stage mesothelioma tumors in mice in just a few days with a treatment combining Rice’s cytokine “drug factory” implants and a checkpoint inhibitor drug.

The researchers administered the drug-producing beads, which are no larger than the head of a pin, next to tumors where they could produce continuous, high doses of interleukin-2 (IL-2), a natural compound that activates white blood cells to fight cancer.

The study, published online today in Clinical Cancer Research, is the latest in a string of successes for the drug-factory technology invented in the lab of Rice bioengineer Omid Veiseh, including Food and Drug Administration (FDA) approval to begin clinical trials of the technology this fall in ovarian cancer patients.

“From the beginning, our objective was to develop a platform therapy that can be used for multiple different types of immune system disorders or different types of cancers,” said Rice graduate student Amanda Nash, who spent several years developing the implant technology with study co-lead author Samira Aghlara-Fotovat, a fellow student in Veiseh’s lab.

First Structure of Key COVID Enzyme at Human Body Temperature

Scientists used x-rays to decipher the three-dimensional structure of the main protease of the virus that causes COVID-19 at different temperatures. The background image shows the full structure at 240 Kelvin (-28°F, cyan stick figure) and 100 K (-280°F, dark blue). The red and green blobs represent differences in the structure at these distinct temperatures. The study allowed the scientists to zero in on subtle shifts that occur in the structure as the temperature changes (inset), potentially pointing to areas of the enzyme that could be targeted with inhibitor drugs to impair its function.
 Source/Credit: Brookhaven National Laboratory

Daniel Keedy, City University of New York

Scientists studying a COVID-19 coronavirus enzyme at temperatures ranging from frosty to human-body warm discovered subtle structural shifts that offer clues about how the enzyme works. The findings, published in IUCrJ, the journal of the International Union of Crystallography, may inspire the design of new drugs to counteract COVID-19—and possibly help head off future coronavirus pandemics.

“No previous study has looked at this important coronavirus enzyme at physiological (or body) temperature,” said Daniel Keedy, a structural biologist at the City University of New York (CUNY), who conducted the study in collaboration with scientists at the U.S. Department of Energy’s Brookhaven National Laboratory.

Most structures to date come from frozen samples—far from the temperatures at which the molecules operate within living cells. “If you are working at physiological temperature, you should get a more realistic picture of what’s happening during an actual infection, because that’s where biology happens,” Keedy said.

In addition, he added, the team used temperature as a tool. “By turning that knob and seeing how the protein reacts, we can learn about its mechanics—how it physically works."

Road signs for immune defense cells

The mechanism of MHC I assembly, epitope editing and quality control within the peptide loading complex (PLC). The fully assembled PLC machinery of antigen processing is formed by the antigen transport complex TAP1/2, the chaperones calreticulin, ERp57, and tapasin, and the heterodimeric MHC I (heavy and light chain in teal and green, respectively).
Credit: Christoph Thomas & Robert Tampé

How do killer T cells recognize cells in the body that have been infected by viruses? Matter foreign to the body is presented on the surface of these cells as antigens that act as a kind of road sign. A network of accessory proteins – the chaperones – ensure that this sign retains its stability over time. Researchers at Goethe University have now reached a comprehensive understanding of this essential cellular quality control process. Their account of the structural and mechanistic basis of chaperone networks has just appeared in the prestigious science journal Nature Communications. These new findings could be harbingers of progress in areas such as vaccine development.

Organisms are constantly invaded by pathogens such as viruses. Our immune system swings into action to combat these pathogens immediately. The innate non-specific immune response is triggered first, and the adaptive or acquired immune response follows. In this second defense reaction, specialized cytotoxic T lymphocytes known as killer T cells destroy cells in the body that have been infected and thus prevent damage from spreading. Humans possess a repertoire of some 20 million T cell clones with varying specificity to counter the multitude of infectious agents that exist. But how do the killer T cells know where danger is coming from? How do they recognize that something is wrong inside a cell in which viruses are lurking? They can't just have a quick peek inside.

New injectable gel offers promise for tough-to-treat brain tumors

Quanyin Hu, an assistant professor in the University of Wisconsin–Madison School of Pharmacy’s Pharmaceutical Sciences Division
Credit: UWM

Like the hardiest weed, glioblastoma almost always springs back — usually within months after a patient’s initial brain tumor is surgically removed. That is why survival rates for this cancer are just 25 percent in one year and plummet to 5 percent by the five-year mark.

One of the challenges of treating this disease is that surgeons can’t always remove every bit of tumor or glioma stem cells that might linger in the brain.

“One characteristic of glioblastoma is that the tumor cells are very aggressive, and they will infiltrate the surrounding tissues. So, the surgeon can’t clearly feel the boundaries between the tumor and the normal tissue, and you cannot remove as much as possible because all the tissues in the brain are extremely important — you certainly don’t want to remove too much,” explains Quanyin Hu, an assistant professor in the University of Wisconsin–Madison School of Pharmacy’s Pharmaceutical Sciences Division. “So, the tumor will come back again, and that sharply decreases the survival rate after treatment.”

But Hu’s Cell-Inspired Personalized Therapeutic (CIPT) Lab has developed a powerful immunity-boosting postoperative treatment that could transform the odds for patients with glioblastoma. Hu and his collaborators published their research on the treatment’s use in mouse models of human glioblastoma this month in the journal Science Translational Medicine.

New inhaled COVID-19 therapeutic blocks viral replication in the lungs

UC Berkeley postdoctoral scholar Chi Zhu is part of a team of researchers who are developing a new COVID-19 therapeutic that can be administered as a nasal spray. The experimental treatment is effective against all SARS-CoV-2 “variants of concern” and could be readily modified to target other RNA viruses.
UC Berkeley photo by Brittany Hosea-Small

Scientists at the University of California, Berkeley, have created a new COVID-19 therapeutic that could one day make treating SARS-CoV-2 infections as easy as using a nasal spray for allergies.

The therapeutic uses short snippets of synthetic DNA to gum up the genetic machinery that allows SARS-CoV-2 to replicate within the body.

In a new study published online in the journal Nature Communications, the team shows that these short snippets, called antisense oligonucleotides (ASOs), are highly effective at preventing the virus from replicating in human cells. When administered in the nose, these ASOs are also effective at preventing and treating COVID-19 infection in mice and hamsters.

“Vaccines are making a huge difference, but vaccines are not universal, and there is still a tremendous need for other approaches,” said Anders Näär, a professor of metabolic biology in the Department of Nutritional Sciences and Toxicology (NST) at UC Berkeley and senior author of the paper. “A nasal spray that is cheaply available everywhere and that could prevent someone from getting infected or prevent serious disease could be immensely helpful.”

Because the ASO treatment targets a portion of the viral genome that is highly conserved among different variants, it is effective against all SARS-CoV-2 “variants of concern” in human cells and in animal models. It is also chemically stable and relatively inexpensive to produce at large scale, making it ideal for treating COVID-19 infections in areas of the world that do not have access to electricity or refrigeration.

Triazavirin to Be Tested for Effectiveness Against Tick-Borne Encephalitis

Triazavirin was developed by scientists of the Ural Federal University and the Ural Branch of the Russian Academy of Sciences.
Credit: UrFU Press Service

The scientific community has provided research recommendations

The Medsintez plant, the manufacturer of the antiviral drug Triazavirin, plans to conduct studies of the drug for effectiveness against tick-borne encephalitis. Aleksandr Petrov, Chairman of the Board of Directors of the Medsintez Plant LLC, notes that the company has already received recommendations from the scientific community. This was reported by TASS.

"The effectiveness of Triazavirin against tick-borne encephalitis is a very interesting topic to study. Scientists are already saying that the drug can be effective against this virus. Currently we are guided by the opinion of scientists, that is why we are considering the possibility of conducting such studies," said Petrov.

He stressed that this year in some regions there is a high activity of ticks and increased detection of cases of encephalitis, that is why Triazavirin research in this area is relevant.

Reference:
Medsintez plant is located in Novouralsk (Sverdlovsk region). It specializes in the production of pharmaceutical products. The plant produces infusion solutions, ready forms of genetically engineered human insulin, solid and liquid forms of drugs. The plant manufactures licensed products and is engaged in the creation of new drugs.

Source/Credit: Ural Federal University

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Researchers discover new leukemia-killing compounds

Natasha Kirienko (left) and Svetlana Panina in Kirienko’s Rice University laboratory in 2019. Kirienko, associate professor of biosciences, and Panina, a former postdoctoral research associate in Kirienko’s lab, collaborated with researchers at the University of Texas MD Anderson Cancer Center to study potential new mitophagy-inducing drugs that could be paired with other chemotherapies to deliver a potent one-two punch to leukemia.
Photo by Jeff Fitlow/Rice University

Researchers from Rice University and the University of Texas MD Anderson Cancer Center have discovered potential new drugs that work in concert with other drugs to deliver a deadly one-two punch to leukemia.

The potential drugs are still years away from being tested in cancer patients, but a recently published study in the journal Leukemia highlights their promise and the innovative methods that led to their discovery.

In previous studies, the research groups of Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva screened some 45,000 small-molecule compounds to find a few that targeted mitochondria. In the new study, they chose eight of the most promising compounds, identified between five and 30 closely related analogs for each and conducted tens of thousands of tests to systematically determine how toxic each analog was to leukemia cells, both when administered individually or in combination with existing chemotherapy drugs like doxorubicin.

“One of the big challenges was to establish optimal conditions and doses for testing on both cancer cells and healthy cells,” said study lead author Svetlana Panina , a researcher at the University of Texas at Austin who conducted the research during her postdoctoral studies at Rice. “The results from our previously published cytotoxicity assay were helpful, but very little is known about these small-molecule compounds. None of them had been thoroughly described in other studies, and we had to essentially start from scratch to determine how much to use, what they do in cells, everything. All the doses and treatment conditions had to be adjusted by multiple preliminary experiments.”

Cancer drug shows potential as treatment for muscular dystrophy

Dr. Farshad Babaeijandaghi
Source UBC

Researchers at UBC’s School of Biomedical Engineering have discovered that an existing cancer drug could have potential as a treatment for muscular dystrophy.

The researchers found that the drug — known as a colony-stimulating factor 1 receptor (CSF1R) inhibitor — helped slow the progress of Duchenne muscular dystrophy in mice by increasing the resiliency of muscle fibers.

The findings were published today in Science Translational Medicine.

“This is a class of drug that is already being used in clinical trials to treat rare forms of cancer,” says Dr. Farshad Babaeijandaghi, a postdoctoral fellow at UBC and first author on the study. “To find that it could potentially serve a double purpose as a treatment for muscular dystrophy is incredibly exciting. It shows a lot of promise, and with further testing, could help extend and improve quality of life for patients.”

Duchenne muscular dystrophy (DMD) is a severe genetic disorder that leads to progressive muscle weakness and degeneration due to disruptions to the protein dystrophin, which helps keep muscle cells intact. It is the most common congenital disease in Canada, affecting about one out of every 3,500 males, and in rarer cases, females.

DMD symptoms typically appear in early childhood, with patients facing increased loss of muscle function as they age. As the disease progresses, many patients are forced to rely on mobility aids, such as a wheelchair, with the disease eventually impacting heart and lung function. While improvements in cardiac and respiratory care have increased life expectancy in recent decades, there is currently no cure.

Chemically modified plant substances work against the hepatitis E virus

Chemically modified rocaglamides prevent certain viruses from multiplying.
Credit: Department of Molecular and Medical Virology

Rocaglamides from mahogany plants raise hope for the development of an antiviral drug.

The hepatitis E virus (HEV) is widespread and so far, there is no effective drug. In the search for this, the so-called rocaglamides have come into focus: plant substances that can inhibit the multiplication of viruses. Researchers from the Molecular and Medical Virology Department at the Ruhr University Bochum (RUB) have examined a library of chemically modified rocaglamides for their antiviral effects, which a team from Boston has created. A group of active substances that has a so-called amidino group stood out. It particularly effectively inhibited virus multiplication. The team around Dimas F. Praditya, Mara Klöhn and Prof. Dr. Eike Steinmann reports in the journal Antiviral Research.

Plant substances inhibit the multiplication of cancer cells and viruses

Rocaglamides are a group of plant substances that are produced by various mahogany plants. It is known that they have an inhibitory effect on the multiplication of some cancer cells. It was not until 2008 that findings on their antiviral effects against RNA viruses were published for the first time: for example, they can inhibit the multiplication of Ebolaviruses, HEV, zikaviruses or Sars-Cov-2.

An Experimental Treatment Failed in Mice, and Researchers Did the Right Thing: They Published About It

Treatment of FOP mice with an antibody to ACVR1 greatly exacerbates abnormal bone formation (heterotopic ossification) following muscle injury. This is a 3D-rendered microCT image in which the heterotopic bone has been colorized green.
Source: University of Connecticut

Blocking the mutant protein with an antibody didn’t stop the strange, abnormal bone growths in mice. But the knowledge gained could steer scientists toward more promising approaches, report researchers from UConn and Alexion Pharmaceuticals in the The Journal of Clinical Investigation.

Fewer than 4,000 people worldwide are afflicted with fibrodysplasia ossificans progressiva (FOP), an inherited disease in which small injuries or bruises to skeletal muscle provoke the growth of massive, abnormal bone and cartilage. Gradually much of the body’s soft tissue turns to bone. Now, researchers at UConn and Alexion Pharmaceuticals who were investigating a potential cure instead found a concerning surprise–blocking the protein responsible for the disease with a monoclonal antibody made the abnormal bone growth worse in mice.

Normally, stem cells help repair muscle damaged by injury or disease. But in people with FOP, certain stem cells get the wrong message from a mutant receptor on their surface. Instead of promoting muscle regeneration, the stem cells develop into bone.

UConn Professor of Molecular and Cell Biology David Goldhamer, Alexion Pharmaceuticals researcher Jeffrey Hunter, and colleagues worked for years to discover a potential antibody therapy for FOP using accurate genetic mouse models of the disease developed by the two groups. The idea was that the antibody would block the mutant receptor and prevent the responsible stem cells from making new bone. But the results were exactly the opposite.

New delivery method allows slow-release of broader array of peptide drugs in the body

Schwendeman Lab.
Image credit: Michigan Photography

A new study from the University of Michigan describes one of the first entirely new drug delivery microencapsulation approaches in decades.

Microencapsulation in biodegradable polymers allows drugs such as peptide therapeutics to be released over time in the body.

Peptides are molecules in the body that are composed of short chains of amino acids, and include messengers, growth factors and well-known hormones such as insulin. Because of their larger size and structure, peptide drugs are rarely given by mouth and must be injected. Microencapsulation is one way to decrease the time needed between injections.

One slow-release delivery method for peptide drugs is to encapsulate them within the type of resorbable polymers often used as dissolving sutures, said study co-author Steven Schwendeman, professor of pharmaceutical sciences and biomedical engineering.

However, development of polymer dosage forms for delivery of certain peptide drugs has been difficult because the currently available methods to microencapsulate the peptide molecules in the polymer require organic solvents and complex manufacturing.

Locking Leukemia’s Cellular Escape Hatch

Kris Wood, PhD, associate professor of
Pharmacology and Cancer Biology

Leukemia starts in cells that would normally develop into different types of blood cells. About 61,000 people in the U.S. are diagnosed each year, and depending on the type of leukemia and the age of the patient, five-year survival rates vary between about 20-80%.

After losing a close friend to an aggressive form of leukemia, acute myeloid leukemia (AML), Kris Wood, PhD, associate professor of pharmacology and cancer biology, devoted his research to helping find better treatment options for people with leukemias and lymphomas. He and his colleagues have discovered a potential new drug therapy that is preparing to enter clinical trials.

A new class of drugs called nuclear exportin inhibitors has recently been approved for use to treat cancers. Nuclear exportins are proteins that shuttle other proteins out of the nucleus of a cell. These new drugs stop the shuttle from leaving the station.

“The idea is that if you treat cells with a drug that blocks a nuclear exportin,” Wood said, “its client proteins become trapped in the nucleus.” And while researchers don’t fully understand why this is therapeutic, it works. Wood and his team investigated the mechanisms behind it. Their results were published in Nature Cancer.

First, they treated AML cells with Selinexor, a nuclear exportin inhibitor. At the same time, they used CRISPR screens to knock out thousands of genes across the genome one at a time to identify genes that made the drug work either much better or much worse when knocked out.

Common drug-resistant superbug develops fast resistance to 'last resort' antibiotic

Pseudomonas under a microscope
Credit: Sean Booth

New research has found that Pseudomonas bacterium develops resistance much faster than usual to a common ‘last-resort’ antibiotic.

A study published today in Cell Reports reveals how populations of a bacterium called Pseudomonas respond to being treated with Colistin, a 'last resort' antibiotic for patients who have developed multi-drug resistant infections.

Antibiotics play a key role in human health by helping to combat bacterial infection, but bacteria can evolve resistance to antibiotics patients rely on. Antibiotic-resistant infections now cause >1 million deaths worldwide per year.

With a small number of ‘last-resort’ antibiotics available, researchers from the University of Oxford are investigating the processes that drive the rise, and fall, of resistance in common bacterial pathogen populations, which is key to tackling the increase in antimicrobial resistance (AMR).

Alzheimer’s disease causes cells to overheat and ‘fry like eggs’

Mammalian cell stained with fluorescence polymeric thermometers and falsely-colored based on temperature gradients. 
Credit: Chyi Wei Chung

The researchers, from the University of Cambridge, used sensors small and sensitive enough to detect temperature changes inside individual cells, and found that as amyloid-beta misfolds and clumps together, it causes cells to overheat.

In an experiment using human cell lines, the researchers found the heat released by amyloid-beta aggregation could potentially cause other, healthy amyloid-beta to aggregate, causing more and more aggregates to form.

In the same series of experiments, the researchers also showed that amyloid-beta aggregation can be stopped, and the cell temperature lowered, with the addition of a drug compound. The experiments also suggest that the compound has potential as a therapeutic for Alzheimer’s disease, although extensive tests and clinical trials would first be required.

The researchers say their assay could be used as a diagnostic tool for Alzheimer’s disease, or to screen potential drug candidates. The results are reported in the Journal of the American Chemical Society.

Common drug offers fertility hope for women with obesity

Researchers may have found a solution to improving fertility in women with obesity, following a successful trial in mice using diabetes medication to reduce blood glucose levels.

The University of Queensland study found the common type 2 diabetes medication, Dapagliflozin, altered reproductive hormones in obese mice, and could be the key to improving fertility in humans.

Professor Chen Chen, from UQ’s School of Biomedical Sciences, said the results were a promising sign, as human and mouse reproductive cycles are similar.

“After eight weeks of treatment, blood glucose levels in the mice normalized, body weight reduced, reproductive cycles recovered, and reproductive hormones and ovulation were largely restored, compared with mice that were not treated,” Professor Chen said.

“The drug we used – Dapagliflozin – is known for reducing blood glucose levels and improving other biomarkers of metabolic health, but its effects on reproductive health and fertility have yet to be fully investigated.

“Our findings suggest that normalizing blood glucose metabolism with Dapagliflozin in obesity may be a promising route for restoring reproductive function, at the very least.”