Reprogramming obesity: New drug from Italian biotech aims to treat the underlying causes of obesity

RNA-based drug is designed to rewire the metabolism to provide lasting weight loss, while preserving muscle mass; weekly jab is in clinical trials, following promising results in preclinical studies

European Association for the Study of Diabetes

Facebook

XLinkedInWeChatBlueskyMessageWhatsAppEmail

Details of a new drug that aims to treat the underlying causes of obesity are being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15-19 September).

The treatment of obesity has been transformed in recent years by glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide, which reduce appetite, slow the release of food from the stomach and increase feelings of fullness.

These drugs are highly effective for weight loss but many people regain weight after stopping treatment. That’s because obesity is driven by more than appetite alone – it also involves disrupted lipid and glucose metabolism, changes in adipose tissue and mitochondrial dysfunction, leaving plenty of room for new approaches, explains Riccardo Panella, co-founder and CEO of Turin-based biotech Resalis Therapeutics.  

The company’s approach involves an antisense oligonucleotide – a small, lab-made fragment of genetic material designed to block a specific RNA in the body.  The new drug, which is called RES-010, is designed to block an RNA molecule called miR-22.

miR22 is a “master controller” of many processes involved in obesity, including lipid metabolism (how the body breaks down and uses fats), the production and activity of mitochondria (the tiny structures that provide cells with energy) and adipose tissue remodelling (changes in how body fat is organised and how it functions), says Dr Panella, who is one of the authors of the new research.

The hope is that by tackling all these factors simultaneously, RES-010, which is administered once a week as a subcutaneous injection, will reprogramme the metabolism, producing long-lasting weight loss.

Pre-clinical studies show that the compound can induce significant weight loss – and that the lost weight isn’t regained when treatment stops.  A phase 1 trial is now under way.1

In tests on obese mice, mice given weekly injections of the drug lost about 12% more weight than untreated mice. The weight loss occurred gradually over the five months of treatment, leading to the animals returning to healthy weight.

“Importantly, the treated mice lost weight despite eating the same amount as the untreated mice, which suggests RES-010 isn’t suppressing appetite but reprogramming the metabolism,” says Dr Panella.

Experiments also showed that mice that had been treated with RES-010 did not regain weight after the drug was stopped.

The team also explored giving RES-010 and semaglutide alone and together to mice and non-human primates (NHPs).

They found that RES-010 selectively targeted fat mass.  This is important because rapid weight loss when on a diet or taking GLP-1 drugs2 can lead to lean mass, which includes muscle and bone, being lost too.

“Lean mass, especially skeletal muscle, is central to strength, stamina and blood sugar regulation, and so its loss is potentially harmful,” says Dr Panella.

NHPs given RES-010 lost 15% fat mass and 1% lean mass over ten weeks.  This compares with 16% fat mass and 8% lean mass for semaglutide alone.

The team also looked at whether the animals regained weight after treatment was stopped.

They observed that while the NHPs given semaglutide alone regained weight after semaglutide was discontinued, the animals receiving the combination treatment did not regain weight after semaglutide was stopped and they remained on RES-010 alone. Moreover, no rebound occurred when RES-010 was also stopped a few weeks later.

No significant side-effects were seen in the mice or the NHPs at therapeutic doses, says Dr Panella.

Tests on animals and non-human organoids have shown how the drug works.

Dr Panella says: “RES-010 works by reprogramming how cells handle fat and energy

“Rather than reducing appetite, it changes the way in which the body uses fats, boosts the production and activity of mitochondria, the ‘batteries’ that power cells, and helps convert white fat, which stores energy, into brown fat, which burns it.

“Because it acts on these fundamental pathways, weight regain is less likely.

“RES-010 is pioneering a new class of RNA medicines that reprogramme the body’s metabolism, with the aim of producing long-lasting weight loss and improved metabolic health by, for example, improving liver health.”

The drug is now being given to humans for the first time, in a phase 1 clinical trial in the Netherlands.

The randomised double-blind, placebo-controlled study, will involve up to 80 participants (including some with overweight or obesity) and assess the safety and side-effects of various doses.  The first participants were treated in November 2024 and the initial results are expected at the beginning of 2026. .

---

Article Publication Date

17-Sep-2025

 

Study assesses cancers in children exposed to medical imaging

Study of nearly 4 million children and adolescents finds that 10% of pediatric blood and bone marrow cancers may have stemmed from radiation exposure.  

University of California - San Francisco

Facebook

XLinkedInWeChatBlueskyMessageWhatsAppEmail

A study led by UC San Francisco and UC Davis has concluded that radiation from medical imaging is associated with a higher risk of blood cancers in children.  

The researchers examined data from nearly 4 million children and estimated that 1 in 10 blood cancers — some 3,000 cancers in all — may be attributable to radiation exposure from medical imaging. The risk increased proportionally based on the cumulative amount of radiation the children received.  

The study, which was funded by the National Institutes of Health (NIH), appears Sept. 17 in The New England Journal of Medicine. 

The investigation is the first comprehensive assessment using data from children and adolescents in North America that quantifies the association between radiation exposure from medical imaging and blood and bone marrow cancers, such as leukemia and lymphoma, which are the most common forms of cancer in children and adolescents.  

Medical imaging saves lives by enabling timely diagnosis and effective treatment, but it also exposes patients to ionizing radiation, a known carcinogen, particularly through computed tomography (CT). 

The authors caution that doctors and parents should avoid excessive radiation doses and minimize exposure when clinically feasible. 

“Children are particularly vulnerable to radiation-induced cancer due to their heightened radiosensitivity and longer life expectancy,” said Rebecca Smith-Bindman, MD, a radiologist and professor of Epidemiology and Biostatistics, as well as Obstetrics, Gynecology and Reproductive Sciences at UCSF and the first author of the paper.   

“While medical imaging can be lifesaving, our findings underscore the critical need to carefully evaluate and minimize radiation exposure during pediatric imaging to safeguard children’s long-term health,” said Smith-Bindman, who is also a member of the Philip R. Lee Institute for Health Policy Studies. “This involves ensuring that imaging is performed only when it provides essential information for the child’s care and, in cases such as CT scans, using the lowest possible radiation doses.”  

Documenting risks in children  

The study uses a retrospective cohort design, looking back at the complete imaging histories of 3.7 million children who were born between 1996 and 2016. The children were treated at six health care systems in the U.S. and Ontario, Canada. Investigators found a significant relationship between cumulative radiation dose and the risk of a hematologic malignancy, which includes tumors affecting the blood, bone marrow, lymph, and lymphatic system.  

The risk of developing cancer varied significantly by imaging modality. CT, which is used to detect many abnormalities such as tumors, heart disease, and injuries of the spinal cord and brain, entails significant radiation exposure. But radiographs, which are used to diagnose both broken bones and pneumonia, expose children to much lower doses.  

Among all the forms of medical imaging, the study found that chest radiography was the most common imaging exam that doctors performed. The most common form of CT was of the head and brain. 

For children who underwent a head CT, the researchers attributed about a quarter of the children’s subsequent hematologic malignancies to radiation exposure. For those who had radiographs, by contrast, they estimated that only a small fraction of the children’s subsequent cancers were associated with radiation exposure.  

Getting one or two head CTs was associated with a 1.8-fold increased risk of a cancer diagnosis, and this rose to 3.5 times for children who received more scans and were therefore exposed to more radiation.  

Altogether, 2,961 hematologic malignancies were diagnosed during the study period. Lymphoid malignancies accounted for 79.3%, while myeloid malignancies and acute leukemia together accounted for 15.5%. About 58% of cancers occurred in males, and about half were diagnosed in children under 5.  

The authors said that up to 10% of hematologic malignancies in children and adolescents could be prevented by reducing unnecessary imaging and optimizing radiation doses. In many cases, the authors said, substituting non-ionizing imaging modalities like ultrasound or MRI may be feasible without compromising diagnostic accuracy. 

Benefits vs. risks  

The authors emphasized that while medical imaging remains an invaluable tool in pediatric care, their findings highlight the need to carefully balance its diagnostic benefits with potential long-term risks. 

“This study provides robust, directly observed evidence of a clear dose-response relationship between radiation from medical imaging and hematologic malignancy risk in children and adolescents,” said Diana Miglioretti, PhD, UC Davis Health professor and chief of the Division of Biostatistics. 

“Our findings align with international research highlighting that children are especially radiosensitive,” Miglioretti added. “It’s crucial for clinicians to weigh the immediate benefits of imaging against potential long-term health risks and to optimize imaging protocols to minimize radiation exposure.”  

Authors: From UCSF, authors included Malini Mahendra, MD, an associate professor of pediatric critical care. Joint senior author is Jason D. Pole, PhD, of ICES (Ontario), the University of Toronto and the University of Queensland, Brisbane, Australia. From UC Davis, authors are Susan A. Alber, PhD; and Jonathan Ducore, MD, MPH. Other authors are with Kaiser Permanente Northern California; Kaiser Permanente Washington, Seattle; Kaiser Permanente Center for Health Research in Portland; Kaiser Permanente Hawaii; the University of Florida; the Marshfield Clinic Research Institute in Wisconsin; the Department of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School; the Department of Radiology at the University of Chicago; and Washington University in St. Louis, MI.  

Funding:  The research was supported by the National Cancer Institute of the National Institutes of Health (NCI R01CA185687 and NCI R50CA211115). The Ontario, Canada portion of the study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care.  

 

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at ucsf.edu, or see our Fact Sheet.

###

 

Follow UCSF
ucsf.edu | Facebook.com/ucsf | YouTube.com/ucsf

---

Journal

New England Journal of Medicine

 

ChatGPT “thought on the fly” when put through Ancient Greek maths puzzle

The Artificial Intelligence chatbot, ChatGPT, appeared to improvise ideas and make mistakes like a student in a study that rebooted a 2,400-year-old mathematical challenge.

University of Cambridge

Facebook

XLinkedInWeChatBlueskyMessageWhatsAppEmail

The experiment, by two education researchers, asked the chatbot to solve a version of the “doubling the square” problem – a lesson described by Plato in about 385 BCE and, the paper suggests, “perhaps the earliest documented experiment in mathematics education”. The puzzle sparked centuries of debate about whether knowledge is latent within us, waiting to be ‘retrieved’, or something that we ‘generate’ through lived experience and encounters.

The new study explored a similar question about ChatGPT’s mathematical ‘knowledge’ – as that can be perceived by its users. The researchers wanted to know whether it would solve Plato’s problem using knowledge it already ‘held’, or by adaptively developing its own solutions.

Plato describes Socrates teaching an uneducated boy how to double the area of a square. At first, the boy mistakenly suggests doubling the length of each side, but Socrates eventually leads him to understand that the new square’s sides should be the same length as the diagonal of the original.

The researchers put this problem to ChatGPT-4, at first imitating Socrates’ questions, and then deliberately introducing errors, queries and new variants of the problem.

Like other Large Language Models (LLMs), ChatGPT is trained on vast collections of text and generates responses by predicting sequences of words learned during its training. The researchers expected it to handle their Ancient Greek maths challenge by regurgitating its pre-existing ‘knowledge’ of Socrates’ famous solution. Instead, however, it seemed to improvise its approach and, at one point, also made a distinctly human-like error.

The study was conducted by Dr Nadav Marco, a visiting scholar at the University of Cambridge, and Andreas Stylianides, Professor of Mathematics Education at Cambridge. Marco is permanently based at the Hebrew University and David Yellin College of Education, Jerusalem.

While they are cautious about the results, stressing that LLMs do not think like humans or ‘work things out’, Marco did characterise ChatGPT’s behaviour as “learner-like”.

“When we face a new problem, our instinct is often to try things out based on our past experience,” Marco said. “In our experiment, ChatGPT seemed to do something similar. Like a learner or scholar, it appeared to come up with its own hypotheses and solutions.”

Because ChatGPT is trained on text and not diagrams, it tends to be weaker at the sort of geometrical reasoning that Socrates used in the doubling the square problem. Despite this, Plato’s text is so well known that the researchers expected the chatbot to recognise their questions and reproduce Socrates’ solution.

Intriguingly, it failed to do so. Asked to double the square, ChatGPT opted for an algebraic approach that would have been unknown in Plato’s time.

It then resisted attempts to get it to make the boy’s mistake and stubbornly stuck to algebra even when the researchers complained about its answer being an approximation. Only when Marco and Stylianides told it they were disappointed that, for all its training, it could not provide an “elegant and exact” answer, did the Chat produce the geometrical alternative.

Despite this, ChatGPT demonstrated full knowledge of Plato’s work when asked about it. “If it had only been recalling from memory, it would almost certainly have referenced the classical solution of building a new square on the original square’s diagonal straight away,” Stylianides said. “Instead, it seemed to take its own approach.”

The researchers also posed a variant of Plato’s problem, asking ChatGPT to double the area of a rectangle while retaining its proportions. Even though it was now aware of their preference for geometry, the Chat stubbornly stuck to algebra. When pressed, it then mistakenly claimed that, because the diagonal of a rectangle cannot be used to double its size, a geometrical solution was unavailable.

The point about the diagonal is true, but a different geometrical solution does exist. Marco suggested that the chance that this false claim came from the chatbot’s knowledge base was “vanishingly small”. Instead, the Chat appeared to be improvising its responses based on their previous discussion about the square.

Finally, Marco and Stylianides asked it to double the size of a triangle. The Chat reverted to algebra yet again – but after more prompting did come up with a correct geometrical answer.

The researchers stress the importance of not over-interpreting these results, since they could not scientifically observe the Chat’s coding. From the perspective of their digital experience as users, however, what emerged at that surface level was a blend of data retrieval and on-the-fly reasoning.

They liken this behaviour to the educational concept of a “zone of proximal development” (ZPD) – the gap between what a learner already knows, and what they might eventually know with support and guidance. Perhaps, they argue, Generative AI has a metaphorical “Chat’s ZPD”: in some cases, it will not be able to solve problems immediately but could do so with prompting.

The authors suggest that working with the Chat in its ZPD can help turn its limitations into opportunities for learning. By prompting, questioning, and testing its responses, students will not only navigate the Chat’s boundaries but also develop the critical skills of proof evaluation and reasoning that lie at the heart of mathematical thinking.

“Unlike proofs found in reputable textbooks, students cannot assume that Chat GPT’s proofs are valid. Understanding and evaluating AI-generated proofs are emerging as key skills that need to be embedded in the mathematics curriculum,” Stylianides said.

“These are core skills we want students to master, but it means using prompts like, ‘I want us to explore this problem together,’ not, ‘Tell me the answer,’” Marco added.

The research is published in the International Journal of Mathematical Education in Science and Technology.

---

Journal

International Journal of Mathematical Education in Science and Technology

DOI

10.1080/0020739X.2025.2543817 

Article Title

An exploration into the nature of ChatGPT’s mathematical knowledge

Article Publication Date

18-Sep-2025

 

Turning seafood waste into sustainable wearable health sensors

Queensland University of Technology

Facebook

Email

 

image: 

 Professor Prashant Sonar with the prototype electronic device created with a material made from seafood waste.

view more 

Credit: QUT

QUT researchers have created a prototype electronic device using a material made from seafood waste, paving the way for safe, flexible and sustainable wearable health sensors.

A team from the QUT Centre for Materials Science has demonstrated that chitosan, a naturally derived, biodegradable biopolymer recovered from seafood waste such as Red Claw shrimp, Rock lobster and squid, can be used with a high-performance conducting polymer film to create a new class of wearable electronic transistors.

The medical-grade polymer samples were supplied by Sunshine Coast-based industry partner Biomedical Chitosan.

The research, published in Small Structures, is a step towards the development of wearable biocompatible  biosensors which could be  able to monitor health in real-time without compromising comfort, safety or the environment.

Lead researcher Professor Prashant Sonar said the study was a significant step in building the next generation of wearable biomedical devices using sustainable electronic approach.

“We have successfully shown that a film made from chitosan, a biopolymer derived from seafood waste, when coated with a conducting polymer, can act as the foundation for flexible transistors,” Professor Sonar said.

“Not only do these devices work electrically, they are biocompatible, meaning they can safely interact with human cells, and they are mechanically strong enough to withstand bending and movement.

“That makes them ideal for future wearable health monitors.”

Chitosan is already widely used in biomedical applications because it is non-toxic and biodegradable.

Using a process called vapor phase polymerisation (VPP) in collaboration with University of South Australia, the researchers coated thin with PEDOT:Tosylate film on chitosan, a material known for high conductivity.

The result was a bendable, skin-friendly electronic film that maintained high performance even when flexed hundreds of times.

QUT PhD researcher Chattarika Khamhanglit, the study’s first author, said the devices showed remarkable mechanical resilience and durability.

“Our prototype retained up to 97 per cent of its electrical performance after repeated bending tests,” Ms Khamhanglit said.
“This gives us confidence these materials could be used in real-world applications such as health sensors that move with the body without losing accuracy.”

The research was led by QUT but also involved key collaboration with Nanyang Technological University (NTU), Singapore, where researchers contributed expertise in organic transistors where the active PEDOT:Tos coated devices conductance varies via electrolyte gating which is needed for biological sensing.

The study also involved partners from the QUT Centre for Biomedical Technologies and Central Analytical Research Facility.

The QUT researchers involved in the research are: Chattarika Khamhanglit, Vithya Sahar Sethu Madhavan, Joshua McDonald, Professor Prashant Sonar from the School of Chemistry and Physics; Antonia RuJia Sun, Associate Professor Indira Prasadam, Professor YuanTong Gu from the School of Mechanical, Medical & Process Engineering; and Dr Yanan Xu from the QUT Central Analytical Research Facility (CARF).

Professor Sonar said biocompatible transistors could become the foundation for wearable biosensors that monitor vital signs or detect disease biomarkers.

“Imagine a lightweight patch that can comfortably adhere to the skin and provide continuous, accurate health information to doctors or patients,” Professor Sonar said.

“This work shows that such devices can be made from safe, sustainable materials sourced from nature.”

The next stage of the research will focus on integrating the chitosan-based devices into biosensing platforms for specific health applications, including non-invasive monitoring and point-of-care diagnostics.

Read the full paper, PEDOT:Tosylate on Biocompatible Chitosan Film by Vapor Phase Polymerization: Promising Technology toward Biocompatible and Wearable Organic Electrochemical Transistor, online.

The device created by QUT researchers using seafood waste.

Credit

QUT

---

Journal

Small Structures

DOI

10.1002/sstr.202400642 

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

PEDOT:Tosylate on Biocompatible Chitosan Film by Vapor Phase Polymerization: Promising Technology toward Biocompatible and Wearable Organic Electrochemical Transistor

 

QUT scientists create material to turn waste heat into clean power

Queensland University of Technology

Facebook

XLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

QUT researchers have developed a new material that achieves record-high thermoelectric performance,

view more 

Credit: QUT

QUT researchers have developed a new material that achieves record-high thermoelectric performance, paving the way for more efficient conversion of waste heat into clean electricity.

The study, published in Energy & Environmental Science, found that adding manganese to silver copper telluride made it the most efficient material of its kind.

The research team, led by Professor Zhi-Gang Chen and Dr Xiao-Lei Shi from QUT’s School of Chemistry and Physics, the ARC Research Hub in Zero-emission Power Generation for Carbon Neutrality, and the QUT Centre for Materials Science, built a prototype device which was used to convert electricity.

First author Nan-Hai Li, also from the School of Chemistry and Physics and the ARC Research Hub, said the tiny change to the material resulted in a product far better at converting heat into electricity.

“We showed it could reach record efficiency levels for its class, and when tested in a prototype device it delivered more than 13 per cent conversion efficiency – putting it alongside the best current technologies,” Dr Li said.

Professor Chen said that 13 per cent conversion efficiency, in simple terms, meant that with the prototype, for every 100 units of heat energy that go into the device, about 13 units were turned into electricity.

“That might not sound like much, but it is a very high number for thermoelectric materials, with most of them only managing a conversion efficiency of a few per cent.”

Professor Chen said the research pointed to new opportunities for clean energy.

“Every day, huge amounts of heat from cars, factories and power stations simply vanish into the air,” Professor Chen said.

“This material gives us a way to capture some of that lost energy and turn it into clean power.”

Associate Professor Shi said the material also had an environmental edge.

“Unlike many other options, this compound doesn’t rely on toxic elements. It’s stable, simple to produce, and therefore a strong candidate for real-world use,” she said.

The full QUT research team was: Nan-Hai Li,  Associate Professor Xiao-Lei Shi, Meng Li, Min Zhang, Wen-Yi Chen, Yong-Qi Chen, Professor Dmitri Golberg,  Dr Dong-Chen Qi, Chao Zhang, Xiaodong Wang and Professor Zhi-Gang Chen. The researchers belonged to the QUT School of Chemistry and Physics, the Central Analytical Research Facility, the QUT Centre for Materials Science and the ARC Research Hub in Zero-emission Power Generation for Carbon Neutrality.

Read the full paper, Manganese doping induced record-high medium-temperature AgCuTe thermoelectrics,  online.

---

Journal

Energy & Environmental Science

DOI

10.1039/D5EE02875B 

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

Manganese doping induced record-high medium-temperature AgCuTe thermoelectrics