Scientists find brain cell switch that could reverse obesity’s effects

Fatty diets and obesity affect the structure and function of astrocytes¹, the star-shaped brain cells located in the striatum, a brain region involved in the perception of pleasure generated by food consumption. What is even more surprising is that by manipulating these astrocytes in vivo in mice can influence metabolism and correct certain cognitive changes associated with obesity (ability to relearn a task, for example). These results, described by scientists from the CNRS² and the Université Paris Cité, were recently published in the journal Nature Communication.

These discoveries reinforce the idea that astrocytes (long neglected in favour of neurons) play a key role in brain function. They also demonstrate, for the first time, the ability of astrocytes to restore cognitive function in the context of obesity, opening up new avenues of research to identify their exact role in energy metabolism.

These conclusions were reached using a combination of ex vivo and in vivo approaches in rodents, including chemogenetic techniques³, brain imaging, locomotion tests, cognitive behaviour and measuring the body's energy metabolism.

Notes

1. Unlike neurons, astrocytes (nervous system cells) do not generate electrical activity, which has made them less easy to study in the past. However, thanks to improvements in observation techniques, we now know that their close cooperation with neurons is essential to the proper functioning of the nervous system.
2. Reporting to l'Unité de biologie fonctionnelle et adaptative (CNRS/Université Paris Cité). Scientists from l'Institut de biologie Paris-Seine (CNRS/Inserm/Sorbonne Université) were also involved.
3. Calcium is an essential chemical element for astrocyte function, enabling synaptic activity to be modulated. The chemogenetic technique employed was based on the use of a virus, to express, in a targeted manner in the astrocytes, a protein that could modulate calcium flow in the cell, rather like a switch. The scientists were thus able to study the effect of these calcium flows on the activity of the astrocytes and surrounding neurons.

Journal Reference:

1. Enrica Montalban, Anthony Ansoult, Daniela Herrera Moro Chao, Cuong Pham, Clara Franco, Andrea Contini, Julien Castel, Rim Hassouna, Marene H. Hardonk, Anna Petitbon, Ewout Foppen, Giuseppe Gangarossa, Pierre Trifilieff, Dongdong Li, Serge Luquet, Claire Martin. Striatal astrocytes modulate behavioral flexibility and whole-body metabolism in mice. Nature Communications, 2025; 16 (1) DOI: 10.1038/s41467-025-60968-y 

Courtesy:

CNRS. "Scientists find brain cell switch that could reverse obesity’s effects." ScienceDaily. ScienceDaily, 8 August 2025. <www.sciencedaily.com/releases/2025/08/250807233048.htm>. 

 

 

Scientists just found a tiny molecule that could change how we lose weight

The obesity rate has more than doubled in the last 30 years, affecting more than one billion people worldwide. This prevalent condition is also linked to other metabolic disorders, including type 2 diabetes, cardiovascular diseases, chronic kidney disease, and cancers. Current treatment options include lifestyle interventions, bariatric surgery, and GLP-1 drugs like Ozempic or Wegovy, but many patients struggle to access or complete these treatments or to maintain their weight loss afterwards.

Salk Institute scientists are looking for a new treatment strategy in microproteins, an understudied class of molecules found throughout the body that play roles in both health and disease. In a new study, the researchers screened thousands of fat cell genes using CRISPR gene editing to find dozens of genes that likely code for microproteins -- one of which they confirmed -- that regulate either fat cell proliferation or lipid accumulation.

The findings, published in Proceedings of the National Academy of Sciences on August 7, 2025, identify new microproteins that could potentially ser

ve as drug targets to treat obesity and other metabolic disorders. The study also showcases the value of CRISPR screening in future microprotein discovery.

"CRISPR screening is extremely effective at finding important factors in obesity and metabolism that could become therapeutic targets," says senior author Alan Saghatelian, a professor and holder of the Dr. Frederik Paulsen Chair at Salk. "These new screening technologies are allowing us to reveal a whole new level of biological regulation driven by microproteins. The more we screen, the more disease-associated microproteins we find, and the more potential targets we have for future drug development."

Current obesity and metabolic disorder therapeutics

When our energy consumption exceeds our energy expenditure, fat cells can grow in both size and number. Fat cells store the excess energy in the form of fatty molecules called lipids. But while some excess storage is manageable, too much can cause fat deposits to accumulate around the body -- leading to whole-body inflammation and organ dysfunction.

Many factors regulate this complex energy storage system. The problem is, how do we find them all, and how do we filter for factors that may make good therapeutic candidates?

This has been a longstanding question for Salk scientists. In fact, Salk Professor Ronald Evans has been working on it for decades. Evans is an expert on PPAR gamma, a key regulator of fat cell development and a potent target for treating diabetes. Several drugs have been developed to target PPAR gamma to treat obesity, but they resulted in side effects like weight gain and bone loss. An ideal PPAR gamma-based obesity therapeutic has yet to hit the market.

When PPAR gamma drugs fell short, GLP-1 drugs entered the scene. GLP-1 is a peptide small enough to be considered a microprotein, and it serves as a blood sugar and appetite regulator. But, like PPAR gamma, GLP-1 drugs have their own shortcomings, such as muscle loss and nausea. Nonetheless, the popularity of GLP-1 drugs demonstrates a promising future for microprotein drugs in the obesity therapeutic space.

 

Saghatelian's team is now searching for the next microprotein therapeutic with new genetic tools that bring microproteins out of the "dark." For many years, long stretches of the genome have been considered "junk" and thus left unexplored. But recent technological advances have allowed scientists to look at these dark sections and find a hidden world of microproteins -- in turn, expanding protein libraries by 10 to 30 percent.

In particular, the Salk team is using innovative CRISPR screening to scour the "dark" for possible microproteins. This approach is enabling the simultaneous discovery of thousands of potential microproteins involved in lipid storage and fat cell biology, accelerating the search for the next PPAR gamma or GLP-1 drug.

How CRISPR screening accelerates the search for microproteins

CRISPR screens work by cutting out genes of interest in cells and observing whether the cell thrives or dies without them. From these results, scientists can determine the importance and function of specific genes. In this case, the Salk team was interested in genes that may code for microproteins involved in fat cell differentiation or proliferation.

"We wanted to know if there was anything we had been missing in all these years of research into the body's metabolic processes," says first author Victor Pai, a postdoctoral researcher in Saghatelian's lab. "And CRISPR allows us to pick out interesting and functional genes that specifically impact lipid accumulation and fat cell development."

This latest research follows up on a prior study from Saghatelian's lab. The previous study identified thousands of potential microproteins by analyzing microprotein-coding RNA strands derived from mouse fat tissues. These microprotein-coding RNA strands were filed away to await investigation into their functions.

The new study first expanded this collection to include additional microproteins identified from a pre-fat cell model. Notably, this new model captures the differentiation process from pre-fat cell to a fully mature fat cell. Next, the researchers screened the cell model with CRISPR to determine how many of these potential microproteins were involved in fat cell differentiation or proliferation.

"We're not the first to screen for microproteins with CRISPR," adds Pai, "but we're the first to look for microproteins involved in fat cell proliferation. This is a huge step for metabolism and obesity research."

Microproteins of interest and next steps

Using their mouse model and CRISPR screening approach, the team identified microproteins that may be involved in fat cell biology. They then narrowed the pool even further with another experiment to create a shortlist of 38 potential microproteins involved in lipid droplet formation -- which indicates increasing fat storage -- during fat cell differentiation.

At this point, the shortlisted microproteins were all still "potential" microproteins. This is because the genetic screening finds genes that may code for microproteins, rather than finding the microproteins themselves. While this approach is a helpful workaround to finding microproteins that are otherwise so small they elude capture, it also means that the screened microproteins require further testing to confirm whether they are functional.

And that's what the Salk team did next. They picked several of the shortlisted microproteins to test and were able to verify one. Pai hypothesizes this new microprotein, called Adipocyte-smORF-1183, influences lipid droplet formation in fat cells (also known as adipocytes).

Verification of Adipocyte-smORF-1183 is an exciting step toward identifying more microproteins involved in lipid accumulation and fat cell regulation in obesity. It also verifies that CRISPR is an effective tool for finding microproteins involved in fat cell biology, obesity, and metabolism.

"That's the goal of research, right?" says Saghatelian. "You keep going. It's a constant process of improvement as we establish better technology and better workflows to enhance discovery and, eventually, therapeutic outcomes down the line."

Next, the researchers will repeat the study with human fat cells. They also hope their success inspires others to use CRISPR screenings to continue bringing microproteins out from the dark -- like Adipocyte-smORF-1183, which until now, was considered an unimportant bit of "junk" DNA.

Further validation or screening of new cell libraries will expand the list of potential drug candidates, setting the stage for the new-and-improved obesity and metabolic disorder therapeutics of the future.

Other authors include Hazel Shan, Cynthia Donaldson, Joan Vaughan, Eduardo V. De Souza, Carolyn O'Connor, and Michelle Liem of Salk; and Antonio Pinto and Jolene Diedrich of Scripps Research Institute.

The work was supported by the National Institutes of Health (F32 DK132927, RC2 DK129961, R01 DK106210, R01 GM102491, RF1 AG086547, NCI Cancer Center P30 014195, S10- OD023689, and S10-OD034268), Ferring Foundation, Clayton Foundation, and Larry and Carol Greenfield Technology Fund.

Journal Reference:

1. Victor J. Pai, Huanqi Shan, Cynthia J. Donaldson, Joan M. Vaughan, Eduardo V. De Souza, Carolyn O’Connor, Michelle Liem, Antonio F. M. Pinto, Jolene Diedrich, Alan Saghatelian. CRISPR–Cas9 screening reveals microproteins regulating adipocyte proliferation and lipid metabolism. Proceedings of the National Academy of Sciences, 2025; 122 (32) DOI: 10.1073/pnas.2506534122 

Courtesy:

Salk Institute. "Scientists just found a tiny molecule that could change how we lose weight." ScienceDaily. ScienceDaily, 10 August 2025. <www.sciencedaily.com/releases/2025/08/250809100924.htm>. 

 

 

 

The parasite that turns off your body’s pain alarm and sneaks in

New research, published in The Journal of Immunology, discovered that a parasitic worm suppresses neurons in the skin to evade detection. The researchers suggest that the worm likely evolved this mechanism to enhance its own survival, and that the discovery of the molecules responsible for the suppression could aid in the development of new painkillers.

Schistosomiasis is a parasitic infection caused by helminths, a type of worm. Infection occurs during contact with infested water through activities like swimming, washing clothes, and fishing, when larvae penetrate the skin. Surprisingly, the worm often evades detection by the immune system, unlike other bacteria or parasites that typically cause pain, itching, or rashes.

In this new study, researchers from Tulane School of Medicine aimed to find out why the parasitic worm Schistosoma mansoni doesn't cause pain or itching when it penetrates the skin. Their findings show that S. mansoni causes a reduction in the activity of TRPV1+, a protein that sends signals the brain interprets as heat, pain, or itching. As part of pain-sensing in sensory neurons, TRPV1+ regulates immune responses in many scenarios such as infection, allergy, cancer, autoimmunity, and even hair growth.

The researchers found that S. mansoni produces molecules that suppress TRPV1+ to block signals from being sent to the brain, allowing S. mansoni to infect the skin largely undetected. It is likely S. mansoni evolved the molecules that block TRPV1+ to enhance its survival.

"If we identify and isolate the molecules used by helminths to block TRPV1+ activation, it may present a novel alternative to current opioid-based treatments for reducing pain," said Dr. De'Broski R. Herbert, Professor of Immunology at Tulane School of Medicine, who led the study. "The molecules that block TRPV1+ could also be developed into therapeutics that reduce disease severity for individuals suffering from painful inflammatory conditions."

The study also found that TRPV1+ is necessary for initiating host protection against S. mansoni. TRPV1+ activation leads to the rapid mobilization of immune cells, including gd T cells, monocytes, and neutrophils, that induce inflammation. This inflammation plays a crucial role in host resistance to the larval entry into the skin. These findings highlight the importance of neurons that sense pain and itching in successful immune responses

"Identifying the molecules in S. mansoni that block TRPV1+ could inform preventive treatments for schistosomiasis. We envision a topical agent which activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni," said Dr. Herbert.

In this study, mice were infected with S. mansoi and evaluated for their sensitivity to pain as well as the role of TRPV1+ in preventing infection. Researchers next plan to identify the nature of the secreted or surface-associated helminth molecules that are responsible for blocking TRPV1+ activity and specific gd T cell subsets that are responsible for immune responses. The researchers also seek to further understand the neurons that helminths have evolved to suppress.

Journal Reference:

1. Juan M Inclan-Rico, Adriana Stephenson, Camila M Napuri, Heather L Rossi, Li-Yin Hung, Christopher F Pastore, Wenqin Luo, De’Broski R Herbert. TRPV1 neurons promote cutaneous immunity against Schistosoma mansoni. The Journal of Immunology, 7 August 2025 DOI: 10.1093/jimmun/vkaf141 

Courtesy:

American Association of Immunologists Inc. "The parasite that turns off your body’s pain alarm and sneaks in." ScienceDaily. ScienceDaily, 12 August 2025. <www.sciencedaily.com/releases/2025/08/250811104224.htm>. 

 

 

Researchers grow 400+ brain cell types—a leap for Alzheimer’s and Parkinson’s research

Nerve cells are not just nerve cells. Depending on how finely we distinguish, there are several hundred to several thousand different types of nerve cell in the human brain according to the latest calculations. These cell types vary in their function, in the number and length of their cellular appendages, and in their interconnections. They emit different neurotransmitters into our synapses and, depending on the region of the brain - for example, the cerebral cortex or the midbrain - different cell types are active.

When scientists produced nerve cells from stem cells in Petri dishes for their experiments in the past, it was not possible to take their vast diversity into account. Until now, researchers had only developed procedures for growing a few dozen different types of nerve cell in vitro. They achieved this using genetic engineering or by adding signalling molecules to activate particular cellular signalling pathways. However, they never got close to achieving the diversity of hundreds or thousands of different nerve cell types that actually exists.

"Neurons derived from stem cells are frequently used to study diseases. But up to now, researchers have often ignored which precise types of neuron they are working with," says Barbara Treutlein, Professor at the Department of Biosystems Science and Engineering at ETH Zurich in Basel. However, this is not the best approach to such work. "If we want to develop cell culture models for diseases and disorders such as Alzheimer's, Parkinson's and depression, we need to take the specific type of nerve cell involved into consideration."

Systematic screening was the key to success

Treutlein and her team have now successfully produced over 400 different types of nerve cell. In doing so, the scientists have paved the way for more precise basic neurological research with cell culture experiments.

The ETH researchers achieved this by working with a culture of human induced pluripotent stem cells that had been generated from blood cells. In these cells, they used genetic engineering to activate certain neuronal regulator genes and treated the cells with various morphogens, a special class of signalling molecules. Treutlein and her team took a systematic approach, using seven morphogens in different combinations and concentrations in their screening experiments. This resulted in almost 200 different sets of experimental conditions.

Morphogens

Morphogens are messengers that are known from research into embryonic development. They are not distributed uniformly within an embryo but occur in a variety of concentrations forming spatial patterns. In this way, they define the position of cells within the embryo, for example whether a cell is near the body axis or in the back, abdomen, head or torso. Accordingly, morphogens help to determine what grows where in the embryo.

The researchers used various analyses to prove that they had produced over 400 different types of nerve cell in their experiment. They examined the RNA (and therefore genetic activity) at the level of individual cells, as well as the external appearance of cells and their function: for example, which type of cell appendage they had in which quantities and which electric nerve impulses they emitted.

The researchers then compared their data with information from databases of neurons from the human brain. By doing this, they were able to identify the types of nerve cell that had been created, such as those found in the peripheral nervous system or brain cells and the part of the brain they come from, whether they perceive pain, cold or movement, and so on.

In-vitro neurons for active ingredient research

Treutlein clarifies that they are still a long way off producing all types of nerve cell that exist in vitro. Nonetheless, the researchers now have access to a much larger number of different cell types than they had before.

They would like to use in-vitro nerve cells to develop cell culture models for studying serious neurological conditions, including schizophrenia, Alzheimer's, Parkinson's, epilepsy, sleep disorders and multiple sclerosis. Cell culture models of this kind are also of great interest in pharmaceutical research for testing the effects of new active compounds in cell cultures without animal testing, with the ultimate aim of one day being able to cure these conditions.

In the future, the cells could also be used for cell replacement therapy, which involves replacing sick or dead nerve cells in the brain with new human cells.

But there is a challenge to overcome before this can happen: the researchers often produced a mixture of multiple different types of nerve cell in their experiments. They are now working to optimise their method so that each experimental condition only produces one specific cell type. They already have some initial ideas as to how this might be achieved.

Journal Reference:

1. Hsiu-Chuan Lin, Jasper Janssens, Benedikt Eisinger, Philipp Hornauer, Ann-Sophie Kroell, Malgorzata Santel, Maria Pascual-Garcia, Ryoko Okamoto, Kyriaki Karava, Zhisong He, Marthe Priouret, Manuel Schr&ouml;ter, J. Gray Camp, Barbara Treutlein. Human neuron subtype programming via single-cell transcriptome-coupled patterning screens. Science, 2025; 389 (6756) DOI: 10.1126/science.adn6121 

Courtesy:
ETH Zurich. "Researchers grow 400+ brain cell types—a leap for Alzheimer’s and Parkinson’s research." ScienceDaily. ScienceDaily, 12 July 2025. <www.sciencedaily.com/releases/2025/07/250711224316.htm>. 

 

Hormone therapy supercharges tirzepatide, unleashing major weight loss after menopause

Using tirzepatide and menopause hormone therapy at the same time leads to increased weight loss in postmenopausal women with overweight or obesity compared to use of tirzepatide treatment alone, according to a study presented at ENDO 2025, the Endocrine Society's annual meeting in San Francisco, Calif.

"These data are the first to show the combined use of tirzepatide and menopause hormone therapy significantly increases treatment effectiveness in postmenopausal women," said Regina Castaneda, M.D., research fellow for the Division of Endocrinology at the Mayo Clinic in Jacksonville, Fla. "Previous studies of the medication semaglutide found similar results. Achieving these outcomes with a second obesity medication may indicate a broader efficacy trend for pairing these two classes of medications."

Menopause-related hormonal changes often result in increased abdominal fat, decreased muscle mass and altered energy expenditure that leads to weight gain and puts millions of women at risk for developing heart disease and other serious health issues.

To confirm the hypothesis that concurrent menopause hormone therapy enhances the effectiveness of tirzepatide for weight loss in postmenopausal women, researchers conducted a real-world study using the electronic medical records of 120 postmenopausal women over a median duration of 18 months. The study included two cohorts: 40 women using menopause hormone therapy concurrently with tirzepatide and 80 women using tirzepatide alone.

The results showed superior total body weight loss percentage for women using tirzepatide plus menopause hormone therapy (17%) compared to those using tirzepatide alone (14%). In addition, a higher percentage of menopause hormone therapy users (45%) also achieved at least 20% total body weight loss, compared to 18% of menopause hormone therapy non-users.

"The information garnered through this new study provides important insights to develop more effective and personalized weight management interventions to reduce a postmenopausal woman's risk of overweight and obesity-related health complications," said Maria Daniela Hurtado Andrade, M.D., Ph.D., assistant professor of medicine and consultant for the Division of Endocrinology at the Mayo Clinic. "This study underscores the urgent need for further research to better understand how obesity medications and menopause hormone therapy work together. Gaining this knowledge could greatly improve the health and well-being of millions of postmenopausal women. It also points to the need for better strategies to make these treatments more accessible and available to those who need them."

This research was funded by the National Institutes of Health Bridging Interdisciplinary Careers in Women's Health Research Grant and the Mayo Clinic Center for Women's Health Research.

Citation:

The Endocrine Society. "Hormone therapy supercharges tirzepatide, unleashing major weight loss after menopause." ScienceDaily. ScienceDaily, 13 July 2025. <www.sciencedaily.com/releases/2025/07/250713031441.htm>. 

 

Not just diabetes: How slightly high blood sugar wrecks men’s sexual health

Metabolic health factors, including small increases in blood sugar, are the main drivers of change in the reproductive systems and sexual functioning of aging men, according to a study presented at ENDO 2025, the Endocrine Society's annual meeting in San Francisco, Calif.

"Although age and testosterone levels have long been considered an impetus for men's declining sexual health, our research indicates that these changes more closely correlate with modest increases in blood sugar and other metabolic changes," said Michael Zitzmann, M.D., Ph.D., professor and doctor of medicine at University Hospital in Muenster, Germany. "This means that men can take steps to preserve or revive their reproductive health with lifestyle choices and appropriate medical interventions."

These conclusions follow a long-term study of healthy men (without diabetes mellitus, heart disease and/or cancer) aged 18-85 that began in 2014 with 200 participants and concluded in 2020 with 117 participants. Researchers studied progressive changes in participants' semen and hormonal profiles, erectile functioning and metabolic health (BMI and blood sugar levels marked by the HbA1c test).

Findings indicated that over time hormone levels and semen parameters stayed largely within normal ranges. However, sperm movement and erectile function declined in men with minimally elevated blood sugar levels that were below the 6.5% HbA1c diabetes threshold. The study also found that while testosterone levels did not have a direct impact on erectile function, they did correlate with participants' libido assessment.

"We're hopeful that the information gleaned from this study will help doctors and their patients formulate effective male sexual health maintenance plans," Zitzmann added. "We now know that it's in our power to retain sexual and reproductive well-being in men, even as they age."

This research was conducted as part of the FAME 2.0 study.

Citation:

The Endocrine Society. "Not just diabetes: How slightly high blood sugar wrecks men’s sexual health." ScienceDaily. ScienceDaily, 13 July 2025. <www.sciencedaily.com/releases/2025/07/250713031439.htm>. 

 

AI sees what doctors miss: Fatty liver disease hidden in chest x-rays

 

Fatty liver disease, caused by the accumulation of fat in the liver, is estimated to affect one in four people worldwide. If left untreated, it can lead to serious complications, such as cirrhosis and liver cancer, making it crucial to detect early and initiate treatment.

Currently, standard tests for diagnosing fatty liver disease include ultrasounds, CTs, and MRIs, which require costly specialized equipment and facilities. In contrast, chest X-rays are performed more frequently, are relatively inexpensive, and involve low radiation exposure. Although this test is primarily used to examine the condition of the lungs and heart, it also captures part of the liver, making it possible to detect signs of fatty liver disease. However, the relationship between chest X-rays and fatty liver disease has rarely been a subject of in-depth study.

Therefore, a research group led by Associate Professor Sawako Uchida-Kobayashi and Associate Professor Daiju Ueda at Osaka Metropolitan University's Graduate School of Medicine developed an AI model that can detect the presence of fatty liver disease from chest X-ray images.

In this retrospective study, a total of 6,599 chest X-ray images containing data from 4,414 patients were used to develop an AI model utilizing controlled attenuation parameter (CAP) scores. The AI model was verified to be highly accurate, with the area under the receiver operating characteristic curve (AUC) ranging from 0.82 to 0.83.

"The development of diagnostic methods using easily obtainable and inexpensive chest X-rays has the potential to improve fatty liver detection. We hope it can be put into practical use in the future," stated Professor Uchida-Kobayashi.

 

Journal Reference:

1. Daiju Ueda, Sawako Uchida-Kobayashi, Akira Yamamoto, Shannon L. Walston, Hiroyuki Motoyama, Hideki Fujii, Toshio Watanabe, Yukio Miki, Norifumi Kawada. Performance of a Chest Radiograph&amp;#8211;based Deep Learning Model for Detecting Hepatic Steatosis. Radiology: Cardiothoracic Imaging, 2025; 7 (3) DOI: 10.1148/ryct.240402 

Courtesy:

Osaka Metropolitan University. "AI sees what doctors miss: Fatty liver disease hidden in chest x-rays." ScienceDaily. ScienceDaily, 27 June 2025. <www.sciencedaily.com/releases/2025/06/250627021845.htm>.

 

 

 

Scientists warn of bat virus just one mutation from infecting humans

 

A group of MERS-related bat viruses could mutate to infect humans. One type, HKU5, is especially concerning due to its ability to bind to ACE2 receptors in animals—and potentially humans next. Credit: Shutterstock

A group of bat viruses closely related to the deadly Middle East respiratory syndrome coronavirus (MERS-CoV) could be one small mutation away from being capable of spilling over into human populations and potentially causing the next pandemic.

A recent study published in the journal Nature Communicationsexamined an understudied group of coronaviruses known as merbecoviruses -- the same viral subgenus that includes MERS-CoV -- to better understand how they infect host cells. The research team, which included scientists at Washington State University, the California Institute of Technology and the University of North Carolina, found that while most merbecoviruses appear unlikely to pose a direct threat to people, one subgroup known as HKU5 possesses concerning traits.

"Merbecoviruses - and HKU5 viruses in particular - really hadn't been looked at much, but our study shows how these viruses infect cells," said Michael Letko, a virologist at WSU's College of Veterinary Medicine who helped to spearhead the study. "What we also found is HKU5 viruses may be only a small step away from being able to spill over into humans."

During the past two decades, scientists have cataloged the genetic sequences of thousands of viruses in wild animals, but, in most cases, little is known about whether these viruses pose a threat to humans. Letko's lab in WSU's Paul G. Allen School for Global Health focuses on closing that gap and identifying potentially dangerous viruses.

For their most recent study, Letko's team targeted merbecoviruses, which have received limited attention apart from MERS-CoV, a zoonotic coronavirus first noted in 2012 that is transmitted from dromedary camels to humans. It causes severe respiratory disease and has a mortality rate of approximately 34%.

Like other coronaviruses, merbecovirusesrely on a spike protein to bind to receptors and invade host cells. Letko's team used virus-like particles containing only the portion of the spike responsible for binding to receptors and tested their ability to infect cells in the lab. While most merbecoviruses appear unlikely to be able to infect humans, HKU5 viruses - which have been found across Asia, Europe, Africa and the Middle East - were shown to use a host receptor known as ACE2, the same used by the more well-known SARS-CoV-2 virus that causes COVID-19. One small difference: HKU5 viruses, for now, can only use the ACE2 gene in bats, but do not use the human version nearly as well.

Examining HKU5 viruses found in Asia where their natural host is the Japanese house bat (Pipistrellus abramus), the researchers demonstrated some mutations in the spike protein that may allow the viruses to bind to ACE2 receptors in other species, including humans. Researchers on another study that came out earlier this year analyzed one HKU5 virus in China that has already been documented to have jumped into minks, showing there is potential for these viruses to cross species-barriers.

"These viruses are so closely related to MERS, so we have to be concerned if they ever infect humans," Letko said. "While there's no evidence they've crossed into people yet, the potential is there -- and that makes them worth watching."

The team also used artificial intelligence to explore the viruses. WSU postdoctoral researcher Victoria Jefferson used a program called AlphaFold 3 to model how the HKU5 spike protein binds to ACE2 at the molecular level, which could help provide a better understanding of how antibodies might block the infection or how the virus could mutate.

Up until this point, such structural analysis required months of lab work and specialized equipment. With AlphaFold, Jefferson generated accurate predictions in minutes. The results matched those recently documented by a research team that used traditional approaches.

Letko noted the study and its methods could be used for future research projects and aid in the development of new vaccines and treatments.

The research was funded through a research project grant from the National Institutes of Health. Jefferson's work was supported by an NIH T32 training grant.

Journal Reference:

1. Nicholas J. Catanzaro, Ziyan Wu, Chengcheng Fan, Victoria Jefferson, Anfal Abdelgadir, Alexandra Sch&auml;fer, Boyd L. Yount, Pamela J. Bjorkman, Ralph Baric, Michael Letko. ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses. Nature Communications, 2025; 16 (1) DOI: 10.1038/s41467-025-60286-3 

Courtesy: 

Washington State University. "Scientists warn of bat virus just one mutation from infecting humans." ScienceDaily. ScienceDaily, 12 June 2025. <www.sciencedaily.com/releases/2025/06/250612081312.htm>. 

 

 

The common blood test that predicts how fast Alzheimer’s hits

Insulin resistance detected by routine triglyceride-glucose (TyG) index can flag people with early Alzheimer's who are four times more likely to present rapid cognitive decline, according to new research presented at the European Academy of Neurology (EAN) Congress 2025.¹

Neurologists at the University of Brescia reviewed records for 315 non-diabetic patients with cognitive deficits, including 200 with biologically confirmed Alzheimer's disease. All subjects underwent an assessment of insulin resistance using the TyG index and a clinical follow-up of 3 years. When patients were divided according to TyG index, those in the highest third of the Mild Cognitive Impairment AD subgroup deteriorated far more quickly than their lower-TyG peers, losing >2.5 points on the Mini Mental State Examination per year (hazard ratio 4.08, 95% CI 1.06-15.73). No such link appeared in the non-AD cohort.

"Once mild cognitive impairment is diagnosed, families always ask how fast it will progress," said lead investigator Dr. Bianca Gumina. "Our data show that a simple metabolic marker available in every hospital laboratory can help identify more vulnerable subjects who may be suitable candidates for targeted therapy or specific intervention strategies."

While insulin resistance has been linked to the onset of Alzheimer's disease, its role in how quickly the condition progresses has received less attention. This study aimed to fill that gap by focusing on its impact during the prodromal mild cognitive impairment (MCI) stage, when patients follow highly variable trajectories. The researchers used the TyG index, which offers a low-cost, routinely available surrogate for insulin resistance, to explore whether metabolic dysfunction could help predict the pace of cognitive decline after diagnosis.

In AD specifically, insulin resistance is believed to impair neuronal glucose uptake, promote amyloid accumulation, disrupt the blood-brain barrier, and fuel inflammation - pathways that are less relevant or differently regulated in other neurodegenerative diseases.

"We were surprised to see the effect only in the Alzheimer's spectrum and not in other neurodegenerative diseases," Dr. Gumina noted. "It suggests a disease-specific vulnerability to metabolic stress during the prodromal window, when interventions may still change the trajectory."

The researchers at University of Brescia, led by Professor Padovani and Professor Pilotto, found that high TyG was also associated with blood-brain barrier disruption and cardiovascular risk factors, yet it showed no interaction with the APOE ε4 genotype, indicating that metabolic and genetic risks may act through distinct pathways.²

Identifying high-TyG patients could refine enrolment for anti-amyloid or anti-tau trials and prompt earlier lifestyle or pharmacological measures to improve insulin sensitivity. The researchers are currently investigating whether TyG levels also track with neuroimaging biomarkers to aid earlier detection and stratification.

"If targeting metabolism can delay progression, we will have a readily modifiable target that works alongside emerging disease-modifying drugs," concluded Dr. Gumina.

References:

1. Gumina B., Galli A., Tolassi C. et al. The Triglyceride-Glucose Index as Predictor of Cognitive Decline in Alzheimer's Spectrum Disorders. Presented at the European Academy of Neurology (EAN) Congress 2025; 23 June 2025; Helsinki, Finland.
2. Padovani A., Galli A., Bazzoli E., et al. (2025). The role of insulin resistance and APOE genotype on blood-brain barrier integrity in Alzheimer's disease. Alzheimer's & Dementia. Advance online publication. https://doi.org/10.1002/alz.14556

Courtesy:

Beyond. "The common blood test that predicts how fast Alzheimer’s hits." ScienceDaily. ScienceDaily, 22 June 2025. <www.sciencedaily.com/releases/2025/06/250622224303.htm>. 

 

 

Artificial intelligence isn’t hurting workers—It might be helping

As artificial intelligence reshapes workplaces worldwide, a new study provides early evidence suggesting AI exposure has not, thus far, caused widespread harm to workers' mental health or job satisfaction. In fact, the data reveals that AI may even be linked to modest improvements in worker physical health, particularly among employees with less than a college degree.

But the authors caution: It is way too soon to draw definitive conclusions.

The paper, "Artificial Intelligence and the Wellbeing of Workers," published June 23 in Nature: Scientific Reports, uses two decades of longitudinal data from the German Socio-Economic Panel. Using that rich data, the researchers -- Osea Giuntella of the University of Pittsburgh and the National Bureau of Economic Research (NBER), Luca Stella of the University of Milan and the Berlin School of Economics, and Johannes King of the German Ministry of Finance -- explored how workers in AI-exposed occupations have fared in contrast to workers in less-exposed roles.

"Public anxiety about AI is real, but the worst-case scenarios are not inevitable," said Professor Stella, who is also affiliated with independent European bodies the Center for Economic Studies (CESifo) and the Institute for Labor Economics (IZA). "So far, we find little evidence that AI adoption has undermined workers' well-being on average. If anything, physical health seems to have slightly improved, likely due to declining job physical intensity and overall job risk in some of the AI-exposed occupations."

Yet the study also highlights reasons for caution.

The analysis relies primarily on a task-based measure of AI exposure -- considered more objective -- but alternative estimates based on self-reported exposure reveal small negative effects on job and life satisfaction. In addition, the sample excludes younger workers and only covers the early phases of AI diffusion in Germany.

"We may simply be too early in the AI adoption curve to observe its full effects," Stella emphasized. "AI's impact could evolve dramatically as technologies advance, penetrate more sectors, and alter work at a deeper level."

Key findings from the study include:

• No significant average effects of AI exposure on job satisfaction, life satisfaction, or mental health.
• Small improvements in self-rated physical health and health satisfaction, especially among lower-educated workers.
• Evidence of reduced physical job intensity, suggesting that AI may alleviate physically demanding tasks.
• A modest decline in weekly working hours, without significant changes in income or employment rates.
• Self-reported AI exposure suggests small but negative effects on subjective well-being, reinforcing the need for more granular future research.

• Due to the data supply, the study focuses on Germany -- a country with strong labor protections and a gradual pace of AI adoption. The co-authors noted that outcomes may differ in more flexible labor markets or among younger cohorts entering increasingly AI-saturated workplaces.

  "This research is an early snapshot, not the final word," said Pitt's Giuntella, who previously conducted significant research into the effect of robotics on households and labor, and on types of workers. "As AI adoption accelerates, continued monitoring of its broader impacts on work and health is essential. Technology alone doesn't determine outcomes -- institutions and policies will decide whether AI enhances or erodes the conditions of work."

   

  Journal Reference:

• Osea Giuntella, Johannes Konig, Luca Stella. Artificial intelligence and the wellbeing of workers. Scientific Reports, 2025; 15 (1) DOI: 10.1038/s41598-025-98241-3 

Courtesy:

University of Pittsburgh. "Artificial intelligence isn’t hurting workers—It might be helping." ScienceDaily. ScienceDaily, 23 June 2025. <www.sciencedaily.com/eleases/2025/06/250623072753.htm>.

 

Recycled plastic is a toxic cocktail: Over 80 chemicals found in a single pellet

A single pellet of recycled plastic can contain over 80 different chemicals. A new study with researchers from University of Gothenburg and Leipzig shows that recycled polyethylene plastic can leach chemicals into water causing impacts in the hormone systems and lipid metabolism of zebrafish larvae.

The plastic pollution crisis has reached global levels, threatening both planetary and human health, and recycling is proposed as one of the solutions to the plastics pollution crisis. However, as plastics contain thousands of chemical additives and other substances that can be toxic, and these are almost never declared, hazardous chemicals can indiscriminately end up in recycled products.

Increasing gene expressions

In a new study, researchers bought plastic pellets recycled from polyethylene plastic from different parts of the world and let the pellets soak in water for 48 hours. After which zebrafish larvae were exposed to the water for five days. The experimental results show increases in gene expression relating to lipid metabolism, adipogenesis, and endocrine regulation in the larvae.

"These short leaching times and exposure times are yet another indicator of the risks that chemicals in plastics pose to living organisms. The impacts that we measured show that these exposures have the potential to change the physiology and health of the fish," says Azora König Kardgar, lead author and researcher in ecotoxicology at the University of Gothenburg.

"Never full knowledge"

Previous research has shown similar effects to humans, including threats to reproductive health and obesity, from exposure to toxic chemicals in plastics. Some chemicals used as additives in plastics and substances that contaminate plastics are known to disturb hormones, with potential impacts on fertility, child development, links to certain cancers, and metabolic disorders including obesity and diabetes.

"This is the main obstacle with the idea of recycling plastic. We never have full knowledge of what chemicals will end up in an item made of recycled plastic. And there is also a significant risk of chemical mixing events occuring, which render the recycled plastic toxic," says Bethanie Carney Almroth, professor at the University of Gothenburg and principal investigator on the project.

Different chemicals

Apart from the study on the impact that recycled plastics have on zebra fish larvae, the researcher also conducted a chemical analysis of the chemicals leaching from the plastic pellets to the water. And they found a lot of different chemical compounds, but the mixture altered between different samples of pellets.

"We identified common plastics chemicals, including UV-stabilizers and plasticizers, as well as chemicals that are not used as plastics additives, including pesticides, pharmaceuticals and biocides. These may have contaminated the plastics during their first use phase, prior to becoming waste and being recycled. This is further evidence of the complicated issue of plastics waste flows, and of toxic chemicals contaminating recycled plastics," says Eric Carmona, researcher at Department of Exposure Science, Helmholtz Centre for Environmental Research in Leipzig.

"Ban hazardous chemicals"

Representatives from the nations of the world are preparing to head to Geneva, Switzerland, in August, for what is planned to be the final negotiating meeting for a Global Plastics Treaty at the Intergovernmental Negotiating Committee under the United Nations Environmental Program. The authors of the work stress that negotiators and decision-makers must include provisions to ban or reduce hazardous chemicals in plastics, and to increase transparency and reporting along plastics value chains. Plastics cannot be recycled in a safe and sustainable manner if hazardous chemicals are not addressed.

"This work clearly demonstrates the need to address toxic chemicals in plastics materials and products, across their life cycle," says Professor Bethanie Carney Almroth. "We cannot safely produce and use recycled plastics if we cannot trace chemicals throughout production, use and waste phases."

Facts: Polyethylene (PE)

Polyethylene, abbreviated PE, is a type of plastic used in a lot of packaging materials like bottle caps, plastic bags, agricultural mulch films, insulation for wiring and cables, pipes, ropes, toys and household items. It is the most widely produced and used polymer. On plastic products made of polyethylene, the number in the recycling code is either 2 or 4.

ournal Reference:

1. Azora K&ouml;nig Kardgar, Eric Carmona, Therese M. Karlsson, Sara Brosch&eacute;, Bethanie Carney Almroth. Effects of leachates from black recycled polyethylene plastics on mRNA expression of genes involved in adipogenesis and endocrine pathways in zebrafish embryos. Journal of Hazardous Materials, 2025; 495: 138946 DOI: 10.1016/j.jhazmat.2025.138946 

Courtesy:

University of Gothenburg. "Recycled plastic is a toxic cocktail: Over 80 chemicals found in a single pellet." ScienceDaily. ScienceDaily, 23 June 2025. <www.sciencedaily.com/releases/2025/06/250623072802.htm>. 

 

 

DNA floating in the air tracks wildlife, viruses -- even drugs

Dublin is known as a city where you can enjoy a few pints of Guiness, get a warm welcome from the locals and hear lively traditional music drifting out of pubs and into the city air.

But it's not just music floating on the breeze. The air of Dublin also contains cannabis, poppy, even magic mushrooms -- at least their DNA.

That's according to a new study that reveals the power of DNA, vacuumed up from the air, which can track everything from elusive bobcats to illicit drugs.

"The level of information that's available in environmental DNA is such that we're only starting to consider what the potential applications can be, from humans, to wildlife to other species that have implications for human health," said David Duffy, Ph.D., a professor of wildlife disease genomics at the University of Florida and lead author of a new study showing the widespread utility of DNA vacuumed from the air.

Housed at UF's Whitney Laboratory for Marine Bioscience, Duffy's lab developed new methods for deciphering environmental DNA, also known as eDNA, to study sea turtle genetics. They've expanded the tools to study every species -- including humans -- from DNA captured in environmental samples like water, soil and sand.

But these errant strands of DNA do not just settle into muddy soil or flow along rivers. The air itself is infused with genetic material. A simple air filter running for hours, days or weeks can pick up signs of nearly every species that grows or wanders nearby.

"When we started, it seemed like it would be hard to get intact large fragments of DNA from the air. But that's not the case. We're actually finding a lot of informative DNA," Duffy said. "That means you can study species without directly having to disturb them, without ever having to see them. It opens up huge possibilities to study all the species in an area simultaneously, from microbes and viruses all the way up to vertebrates like bobcats and humans, and everything in between."

As a proof of concept, the researchers showed that they could pick up signs of hundreds of different human pathogens from the Dublin air, including viruses and bacteria. Such surveillance could help scientists track emerging diseases. The same method can track common allergens, like peanut or pollen, more precisely than is currently possible, the scientists discovered.

In another test of the power of eDNA, Duffy's lab was also able to identify the origin of bobcats and spiders whose DNA was hoovered up from air in a Florida forest. With little more than an air filter, scientists could track endangered species and identify where they came from, all without having to lay eyes on skittish animals or root around forest floors for scat samples. When trying to save and conserve wildlife, knowing where an animal originates from can be as important as knowing where it currently is.

This powerful analysis was paired with impressive speed and efficiency. The team demonstrated that a single researcher could process DNA for every species in as little as a day using compact, affordable equipment, and software hosted in the cloud. That quick turnaround is orders of magnitude faster than would have been possible just a few years ago and opens up advanced environmental studies to more scientists around the world. The same tools can potentially identify sensitive human genetic data, which is why Duffy and his collaborators have called for ethical guardrails for the rapidly developing field of eDNA.

"It seems like science fiction, but it's becoming science fact," Duffy said. "The technology is finally matching the scale of environmental problems."

Journal Reference:

1. Orestis Nousias, Mark McCauley, Maximilian R. Stammnitz, Jessica A. Farrell, Samantha A. Koda, Victoria Summers, Catherine B. Eastman, Fiona G. Duffy, Isabelle J. Duffy, Jenny Whilde, David J. Duffy. Shotgun sequencing of airborne eDNA achieves rapid assessment of whole biomes, population genetics and genomic variation. Nature Ecology & Evolution, 2025; DOI: 10.1038/s41559-025-02711-w    

 Citation:

University of Florida. "DNA floating in the air tracks wildlife, viruses -- even drugs." ScienceDaily. ScienceDaily, 3 June 2025. <www.sciencedaily.com/releases/2025/06/250603114822.htm>.

Tea, berries, dark chocolate and apples could lead to a longer life span, study shows

New research has found that those who consume a diverse range of foods rich in flavonoids, such as tea, berries, dark chocolate, and apples, could lower their risk of developing serious health conditions and have the potential to live longer.

The study was led by a team of researchers from Queen's University Belfast, Edith Cowan University Perth (ECU), and the Medical University of Vienna and Universitat Wien.

The findings reveal that increasing the diversity of flavonoids within your diet could help prevent the development of health conditions such as type 2 diabetes, cardiovascular disease (CVD), cancer and neurological disease.

Flavonoids are found in plant foods like tea, blueberries, strawberries, oranges, apples, grapes, and even red wine and dark chocolate.

Published in Nature Food, the study tracked over 120,000 participants aging from 40 to 70 years old for over a decade. It is the first study of its kind to suggest that there is a benefit to consuming a wide range of flavonoids beyond that of simply consuming a high quantity.

ECU Research Fellow, first author and co-lead of the study Dr Benjamin Parmenter, made the initial discovery that a flavonoid-diverse diet is good for health.

"Flavonoid intakes of around 500 mg a day was associated with a 16% lower risk of all-cause mortality, as well as a ~10% lower risk of CVD, type 2 diabetes, and respiratory disease. That's roughly the amount of flavonoids that you would consume in two cups of tea."

Dr Parmenter added, however, that those who consumed the widest diversity of flavonoids, had an even lower risk of these diseases, even when consuming the same total amount. For example, instead of just drinking tea, it's better to eat a range of flavonoid-rich foods to make up your intake, because different flavonoids come from different foods.

"We have known for some time that higher intakes of dietary flavonoids, powerful bioactives naturally present in many foods and drinks, can reduce the risk of developing heart disease, type 2 diabetes, and neurological conditions like Parkinson's," study co-lead Professor Aedín Cassidy from the Co-Centre for Sustainable Food Systems and Institute for Global Food Security at Queen's said.

"We also know from lab data and clinical studies that different flavonoids work in different ways, some improve blood pressure, others help with cholesterol levels and decrease inflammation. This study is significant as the results indicate that consuming a higher quantity and wider diversity has the potential to lead to a greater reduction in ill health than just a single source."

Professor Tilman Kuhn from the Medical University of Vienna, Universitat Wien and Queen's University Belfast was also a co-lead author, noted that the importance of diversity of flavonoid intake has never been investigated until now, making this study very significant as the findings align with popular claims that eating colourful foods are invaluable to maintain good health.

"Eating fruits and vegetables in a variety of colours, including those rich in flavonoids, means you're more likely to get the vitamins and nutrients you need to sustain a healthier lifestyle," he said.

The first-ever dietary guidelines for flavonoids were released recently recommending increasing the consumption of flavonoids to maintain health.

"Our study provides inaugural evidence that we may also need to advise increasing diversity of intake of these compounds for optimal benefits," Dr Parmenter said.

"The results provide a clear public health message, suggesting that simple and achievable dietary swaps, such as drinking more tea and eating more berries and apples for example, can help increase the variety and intake of flavonoid-rich foods, and potentially improve health in the long-term," Professor Cassidy added.

Journal Reference:

1. Benjamin H. Parmenter, Alysha S. Thompson, Nicola P. Bondonno, Amy Jennings, Kevin Murray, Aurora Perez-Cornago, Jonathan M. Hodgson, Anna Tresserra-Rimbau, Tilman Kühn, Aedín Cassidy. High diversity of dietary flavonoid intake is associated with a lower risk of all-cause mortality and major chronic diseases. Nature Food, 2025; DOI: 10.1038/s43016-025-01176-1 

Courtesy:

Edith Cowan University. "Tea, berries, dark chocolate and apples could lead to a longer life span, study shows." ScienceDaily. ScienceDaily, 3 June 2025. <www.sciencedaily.com/releases/2025/06/250603115028.htm>. 

Personalized gene editing saved a baby, but the tech’s future is uncertain

When a baby born in Philadelphia was announced as the first person to get a gene therapy designed just for him, many people hailed the achievement as a starting point to treat virtually any genetic disease.

But there is a long road that researchers and regulators need to pave before other people with genetic disorders can get bespoke gene therapies.

Here’s what you need to know about this personalized therapy and how it may affect gene therapy moving forward.

What led to this pioneering gene editing?

On May 15, doctors and researchers at Children’s Hospital of Philadelphia (CHOP) and colleagues described the personalized gene therapy in the New England Journal of Medicine. The treated child, KJ Muldoon, has a disorder that prevents his liver from converting ammonia from broken-up proteins to urea. Urea is flushed from the body in urine.

KJ’s form of the disease stems from a mutation in both copies of his CPS1 gene. That gene contains instructions for building an enzyme called carbamoyl-phosphate synthetase 1 that is important in the urea cycle — the conversion of ammonia to urea. Without the enzyme, ammonia levels shoot up and can cause brain and nerve damage and death. This deficiency affects about 1 in 1.3 million people, about half of whom die in early infancy. Low protein diets, medications that help lower ammonia levels and ultimately liver transplants are used to treat the condition, though these measures may not entirely cure the disorder.

KJ was born prematurely in August and was too small for a liver transplant. Medications and extremely low protein diets helped keep ammonia levels in his blood down. But the levels often spiked, and doctors worried he could be left with permanent brain damage or die.

Cardiologist Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine and pediatrician and medical geneticist Rebecca Ahrens-Nicklas of CHOP had already been practicing for such a scenario. They quickly assembled a coalition of academic and industry scientists to manufacture the gene therapy and make sure it was safe to give to a person, Musunuru said in a news briefing May 12.

The team also applied to the U.S. Food and Drug Administration for permission to treat the baby. The FDA recognized that “KJ was very, very sick and there wasn’t time for business as usual,” Musunuru said. The agency approved the treatment within one week of getting the application.

KJ has gotten three infusions of his personalized gene therapy. He isn’t cured — it’s not known whether all the cells in his liver have the corrective edits. Even some patients with liver transplants can have ammonia spikes after infections. But KJ can eat more protein and needs much less medication to keep his ammonia levels in check, Ahrens-Nicklas said. 

What is the personalized gene therapy?

KJ’s gene therapy is based on CRISPR, a targeted gene-editing system which is being developed to treat cancers and a wide variety of genetic diseases. This child got a molecular pencil version of CRISPR called a base editor. That editor chemically erased a mutation in KJ’s broken CPS1 gene and wrote in the correct DNA letter, or base. Base editors are being used as possible treatments for high cholesterol and other conditions. (Musunuru is a founder of the company developing the cholesterol gene therapy.)

This therapy started with messenger RNA, or mRNA, instructions for making the base editor. Messenger RNA is a go-between molecule, a copy of DNA instructions for building a protein. The mRNA is read by cellular machinery and used to produce the protein, which then carries out a particular job. In this case, making the base editor that would correct the typo in KJ’s gene.

The researchers encased mRNA instructions for making the base editor in a lipid nanoparticle, which is “basically like a soap bubble,” says Petros Giannikopoulos, a molecular pathologist at the University of California, Berkeley’s Innovative Genomics Institute. Giannikopoulos was involved in testing KJ’s base editor to make sure it didn’t cause unintended changes elsewhere in his DNA. COVID mRNA vaccines made by Moderna and Pfizer-BioNTech use similar lipid nanoparticle technology to deliver mRNA to cells. In KJ’s case, the nanoparticles specifically directed the therapy to the liver.

Fixing a DNA typo

Researchers used a CRISPR base editor to repair a typo in one baby’s gene, in this case changing an incorrect adenine (A) to the correct guanine (G). A guide RNA (orange) shepherds the base editor to the typo. The base editor is a version of a DNA-cutting enzyme called CRISPR/Cas9 that has been altered so that it nicks one of two DNA strands at the typo (therefore, called Cas9 nickase). Tacked on to the Cas9 nickase is another enzyme called a DNA adenine deaminase. It chemically converts the DNA base adenine (A) to inosine (I). Inosine isn’t a usual DNA building block so DNA repair enzymes in a cell convert it to guanine (G), fixing the typo.

J. Hirshfeld

Researchers tested the base editor in lab-grown cells in a dish. They then gave doses of the therapy to crab-eating macaques to test for toxicity. The team also genetically engineered mice to carry KJ’s mutation, then used the base editor to correct the DNA typo. It took only six months to develop and test the therapy.

KJ got his first intravenous infusion containing the therapy in February. He got a very low dose to start with. Two subsequent doses have been higher. The researchers will continue to monitor KJ, and he soon may be able to leave the hospital where he has lived since birth.

What makes KJ’s case special?

“What was very unique about this was that the therapy was manufactured for an individual patient,” Giannikopoulos says. “This child had a specific mutation…. The therapy was designed for that specific mutation. That was why this was so monumental.”

Previous CRISPR and other gene therapies, including one approved by the FDA to treat sickle cell disease and beta-thalassemia, are proactive, he says. That means “we make and preapprove something, and then wait for the patients to come along” whose mutations match the therapy. KJ’s treatment, in contrast, is reactive. “The patient was diagnosed. We sequenced and found the defect in the genome. And then we designed and manufactured and did all the work to target that specific mutation.”

That personalized approach could be used for many people with super rare diseases.

“I don’t think I’m exaggerating when I say that this is the future of medicine,” Musunuru said in the news briefing. “This is a step towards the use of genetic editing therapies to treat a wide variety of rare genetic disorders for which there are currently no definitive medical treatments.”

Giannikopoulos agrees. “What happened at CHOP was basically the birth of a new medical subspecialty,” he says.

 

Can every genetic disease be treated this way?

Probably not all of them, Giannikopoulos says. There are more than 7,000 known genetic diseases. He estimates that 15 to 20 percent of those might be fixable using currently available gene-editing technology. Ones that are caused by single letter typos in a single gene might be correctable using a base editor.

Other CRISPR editors, including a very versatile version called a prime editor, potentially can repair many types of mutations, including small deletions. Cambridge, Mass.–based Prime Medicine announced in a news release May 19 that it had successfully treated a person with a different rare disease using prime editing.

Scientists must also be able to easily get the editor where it needs to go. Diseases that affect easily accessible organs may be the most treatable, Giannikopoulos says. Immune system or blood disorders may be fixed by removing stem cells from the bone marrow, editing them in the lab and then returning them to the patient. Other organs such as the skin, eye or liver (as in KJ’s case) are relatively easy to deliver gene therapy to inside the body. Other gene therapies delivered inside the body include an approved treatment for Duchenne muscular dystrophy.

But diseases that affect multiple organs at once or those that affect hard-to-reach organs might not be easily treated. For instance, “we’re not very good at targeting the kidney right now,” Giannikopoulos says.

When to deploy gene therapy also matters. “For some diseases, you might need to intervene, maybe in utero, but we haven’t gotten there yet.”

“You’ve also got to understand the disease well enough to be able to intervene. Because [for] some diseases, we know what the mutation is, but we don’t really understand how the mutation is causing trouble.”

What else is needed for personalized gene therapy to become widespread?

Changes in regulations would probably be necessary, Giannikopoulos says. Currently, gene therapies are usually approved for correcting a specific mutation. But some genes may have hundreds of disease-causing mutations, so only a subset of people with a particular disease may be eligible.

Instead, Giannikopoulos and other researchers argue that the general procedure and materials, including the delivery vehicle and gene editor, should be treated as a platform or umbrella therapy. That umbrella intervention would be tested for safety and efficacy and then could be deployed as needed for a patient’s particular mutation. “Otherwise, if everything needs to be repeated in terms of the safety and efficacy for every one of these tens of thousands or potentially hundreds of thousands of specific mutations, then we’ll never get there,” Giannikopoulos says.

It may also be a struggle to get insurance to pay for expensive one-off gene therapies, he says. Funds have been a common and concerning theme for gene therapy. Even when therapies have been proven to work, companies often don’t have the resources to conduct clinical trials to get FDA approval, or to keep the treatments on the market once they have been approved. For instance, Prime Medicine is no longer developing its just-announced gene therapy.

Drastic cuts in research funding may also hinder early gene therapy development in academic laboratories in the United States.

Standardized playbooks for designing and implementing gene therapies are also needed because many doctors want to treat patients with genetic diseases, but don’t have the know-how, Giannikopoulos says. He and Musunuru are part of the U. S. National Institutes of Health–funded Somatic Cell Genome Editing Consortium that is putting together such playbooks. “That’s going to be really how to scale this, [by] teaching everybody how to fish around the world.”

Questions or comments on this article? E-mail us at feedback@sciencenews.org | Reprints FAQ

 

Citations

K. Musunuru et al. Patient-specific in vivo gene editing to treat a rare genetic disease. New England Journal of Medicine. Published online May 15, 2025. doi: 10.1056/NEJMoa2504747.

 

Couresty: https://www.sciencenews.org/article/personalized-crispr-gene-edit-therapy 

Further translation of the language of the genome

 

New research has uncovered more about the complexity of human gene regulation by identifying certain sequences of proteins called transcription factors that bind to DNA and regulate the expression of human genes.

Published today (9 April) in Nature, researchers from the Wellcome Sanger Institute, the University of Cambridge and their collaborators explored how DNA-guided transcription factors interact with each other.

This research adds to the groundwork of understanding the complex language of the gene regulatory code, and how DNA sequence patterns located close to our genes influence human development and disease risk.

Each gene has a regulatory region that contains instructions on when and where the gene is expressed. This information is written in a code that is read by transcription factors, which bind to specific DNA sequences and either increase or decrease the gene's expression.

Previous research has explored the 'language' of the genome -- the regulatory code that controls gene expression. It found that cooperation between multiple transcription factors is a key feature of transcription factor-DNA binding, with DNA actively facilitating interactions between various transcription factors.¹ With the regulatory code being far more complex than the genetic code, which explains how DNA sequence determines the structure of proteins, researchers are aiming to understand the regulatory language in more detail, focusing on the 'words' and 'grammar' -- such as the transcription factors -- that influence when and where genes are expressed.

This deeper understanding is crucial for uncovering how cells develop into specific types, how organs form and where they are located in the body during embryonic development, and for understanding what goes wrong in disease.

The interactions between transcription factors guided by DNA are poorly understood. In a new study, researchers from the Sanger Institute and the University of Cambridge used two novel algorithms to analyse 58,000 pairs of transcription factors from human cells. They did this to identify how and where transcription factors interact with each other to bolster their understanding of the genomic language.²

The researchers' results reveal new patterns and preferences in how certain transcription factors interact with each other -- also known as 'motifs'. In this study, the researchers estimate that they identified between 18 and 47 per cent of all human transcription factor pair motifs, greatly adding to their understanding of the regulatory code.

The team found that certain motifs they identified are present in developmental enhancers -- DNA regulatory elements that activate transcription of a gene -- that control important stages such as development of fingers. For example, the research notes that certain sequences of transcription factor motifs, or 'words' in the language, influence whether or not someone develops polydactyly -- too many fingers -- or syndactyly -- a fusion of fingers.

The findings also have implications for how scientists will use computational models -- such as artificial intelligence -- to predict protein structures in the future. Whilst these tools can predict the overall structure, they often cannot look into smaller details, such as how transcription factors interact with each other on DNA. These small interactions can have a big impact on human development, but computational models cannot always predict this. The researchers hope that future models will be able to incorporate the more minute transcription factor details to better predict protein structure and protein-DNA interactions.

This research marks a step forward in studying the smaller 'words' in the language of gene expression. By identifying small but key motifs in the genome, this research will help scientists understand and interpret the mechanisms influenced by transcription factors, particularly in the non-coding regions of the genome. These regions -- which make up 99 per cent of the genome -- do not code for proteins but still play a significant role in regulation of gene expression, and risk for development of disease.

Dr Ilya Sokolov, an author of the study at the Wellcome Sanger Institute, said: "By gaining a deeper understanding of how transcription factors interact when guided by DNA, we hope our research will shed light on the molecular basis of the regulatory code, particularly in the context of developmental disorders. These interactions are evolutionarily conserved across mammals and offer several advantages in development, from incorporating positional information to creating sharper gene expression responses. With advanced insights into the regulatory code, we are excited to help drive future research that will improve our understanding of human development and developmental disorders."

Professor Jussi Taipale, senior author of the study and Group Leader at the Wellcome Sanger Institute, said: "The human genome's regulatory code is very complex, far more complex than the genetic code, and this research into transcription factor interactions unlocks deeper insights into the 'language' of the genome. Not only does our study provide more information into patterns of human development but it paves the way for future work with computational models that can hopefully incorporate these new data to better understand gene regulation."

Notes

1. Arttu Jolma, Yimeng Yin, Kazuhiro R. Nitta, Kashyap Dave, Alexander Popov, Minna Taipale, Martin Enge, Teemu Kivioja, Ekaterina Morgunova, Jussi Taipale.(2015) 'DNA-dependent formation of transcription factor pairs alters their binding specificity.'Nature. DOI: 10.1038/nature15518
2. The researchers expressed a set of human transcription factors -- enriched in proteins that are conserved in mammals -- in Escherichia coli, combined them into a total of 58,754 transcription factor (TF) pairs and analysed their interactions by CAP-SELEX -- consecutive affinity purification evolution of ligands by exponential enrichment. CAP-SELEX is a method which enables the discovery of TF-TF-DNA binding preferences.

Journal Reference:

1. Zhiyuan Xie, Ilya Sokolov, Maria Osmala, Xue Yue, Grace Bower, J. Patrick Pett, Yinan Chen, Kai Wang, Ayse Derya Cavga, Alexander Popov, Sarah A. Teichmann, Ekaterina Morgunova, Evgeny Z. Kvon, Yimeng Yin, Jussi Taipale. DNA-guided transcription factor interactions extend human gene regulatory code. Nature, 2025; DOI: 10.1038/s41586-025-08844-z 

Courtesy:

Wellcome Trust Sanger Institute. "Further translation of the language of the genome." ScienceDaily. ScienceDaily, 9 April 2025. <www.sciencedaily.com/releases/2025/04/250409155027.htm>.

 

 

 

 

Novel drug delivery platform paves way to potential new treatments for Alzheimer's, other brain-related disorders

 

Oregon State University researchers have discovered a way to get anti-inflammatory medicine across the blood-brain barrier, opening the door to potential new therapies for a range of conditions, including Alzheimer's disease, multiple sclerosis, Parkinson's disease and cancer cachexia.

The delivery method involves specially engineered nanoparticles, tiny bits of matter no larger than 100 billionths of a meter.

Tested in a mouse model, the dual peptide-functionalized polymeric nanocarriers reached their intended destination, the hypothalamus, and delivered a drug that inhibits a key protein associated with inflammation.

"Our work presents a significant breakthrough," said Oleh Taratula, professor in the OSU College of Pharmacy.

Findings were published today in Advanced Healthcare Materials.

The hypothalamus is a small but vital part of the brain situated below the thalamus and above the brainstem, and it plays a key role in maintaining homeostasis -- the body's internal balance. It regulates body temperature, manages sleep cycles, hormone production and emotional responses, and controls hunger and thirst.

In this study, researchers specifically looked at the hypothalamus as it pertains to cachexia, a deadly weight-loss condition associated with cancers of the ovaries, stomach, lungs and pancreas and other chronic conditions such as renal failure, cystic fibrosis, Crohn's disease, rheumatoid arthritis and HIV.

People with cancer cachexia will lose weight even if they eat, and not just fat but muscle mass as well. The debilitating syndrome affects up to 80% of advanced cancer patients and kills as many as 30% of the cancer patients it afflicts.

"Inflammation of the hypothalamus plays a pivotal role in dysregulating those patients' appetite and metabolism," Taratula said. "As cachexia progresses, it significantly impacts quality of life, treatment tolerance and overall survival chances."

The systemic delivery of anti-inflammatory agents, including the IRAK4 inhibitors used in this research, to the hypothalamus presents significant challenges, Taratula said, mainly because of the restrictive nature of the blood-brain barrier.

The blood-brain barrier, often referred to as the BBB, is a protective shield separating the brain from the bloodstream. The BBB is made up of tightly packed cells lining the blood vessels in the brain and controls what substances can move from the blood to the brain.

It allows essential nutrients like oxygen and glucose to pass through and blocks harmful substances such as toxins and pathogens, keeping the brain safe from infections and damage. But it can also deny entry to therapeutic agents.

"An additional hurdle, even if you can get through the BBB to the hypothalamus, is hitting the bullseye within the hypothalamus -- the activated microglia cells that act as key mediators of inflammation," Taratula said. "Our nanocarriers show a dual-targeting capability, and once in the microglia, drug release is triggered by elevated intracellular glutathione levels. We demonstrated, for the first time, that nanocarriers can successfully deliver an IRAK4 inhibitor to the hypothalamus of mice with cancer cachexia."

The scientists observed substantial reductions in key inflammatory markers in the hypothalamus, and the nanocarriers led to a 94% increase in food intake and significantly preserved body weight and muscle mass. And the implications extend far beyond cancer cachexia, Taratula added.

"The nanoplatform's ability to deliver therapeutics across the BBB and target microglia opens new possibilities for treating neurological conditions characterized by brain inflammation, including Alzheimer's disease and multiple sclerosis," he said.

Taratula was joined in the study by College of Pharmacy colleagues Yoon Tae Goo, Vladislav Grigoriev, Tetiana Korzun, Kongbrailatpam Shitaljit Sharma, Prem Singh and Olena Taratula, and by Daniel Marks from Endevica Bio.

The National Cancer Institute of the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Research Foundation of Korea funded the research.

Journal Reference:

1. Yoon Tae Goo, Vladislav Grigoriev, Tetiana Korzun, Kongbrailatpam Shitaljit Sharma, Prem Singh, Olena R. Taratula, Daniel L. Marks, Oleh Taratula. Blood‐Brain Barrier‐Penetrating Nanocarriers Enable Microglial‐Specific Drug Delivery in Hypothalamic Neuroinflammation. Advanced Healthcare Materials, 2025; DOI: 10.1002/adhm.202500521 

Courtesy:

Oregon State University. "Novel drug delivery platform paves way to potential new treatments for Alzheimer's, other brain-related disorders." ScienceDaily. ScienceDaily, 9 April 2025. <www.sciencedaily.com/releases/2025/04/250409115422.htm>.