Category: 8. Health

The push by the nation’s leading pediatric professional organization to give weight-loss drugs to adolescents has led some in the field to urge caution.

About 1 in 5 children in the US have obesity, according to federal data published in 2024. Cardiometabolic concerns such as type 2 diabetes, high blood pressure, and fatty liver disease are common in this patient population, according to the CDC.

For these reasons, some say the potential harms of untreated childhood obesity mean weight-loss drugs such as semaglutide are a game changer. The American Academy of Pediatrics (AAP)’s new guidelines, for example, “highlight the urgency of providing immediate, intensive obesity treatment to each patient as soon as they receive the diagnosis of obesity.” 

Others agree there is an urgent need to treat childhood obesity but argue there are still not enough long-term data on these drugs in youths, and there is not enough emphasis on prevention.

Spike in Prescribing

In late 2023, just after semaglutide, a GLP-1 receptor agonist was approved for obesity treatment in adolescents, the AAP issued revised clinical practice guidelines for childhood obesity, its first update on the condition since December 2007. Guidance went from watchful waiting and lifestyle modifications to initiating pharmacotherapy immediately upon diagnosis in adolescents with obesity aged 12 years or older, and to combine the medication with intensive health behavior and lifestyle therapy (IHBLT).

Since the update, there has been an increase in weight-loss drug prescribing in adolescents with obesity, especially in those with the severest forms, according to a new study published in Pediatrics OpenScience.

Using electronic health records from 310,503 outpatient visits conducted between 2021 and 2024 for children (36.9%) and adolescents (63.1%) with obesity but without type 2 diabetes, the study’s investigators found that the likelihood of the child receiving pharmacotherapy increased immediately (odds ratio [OR], 1.65; 95% CI, 1.23-2.21) and monthly since the guidelines release (OR, 1.05; 95% CI, 1.03-1.07).

“We do report there was a 65% increase in prescribing of anti-obesity medications but the [number] was very, very low — only 0.4% of eligible children started anti-obesity medications after their visit [to their clinician’s office],” study co-author Davene Wright, PhD, associate professor of population medicine at Harvard Pilgrim Health Care Institute in Boston, said in an interview.

“Most of these medications are being used in adolescents with type 3 obesity,” she said, noting that those with severe obesity were 35.7% of the entire sample.

Lack of Data

The American Medical Association issued a stern warning against rushing into prescribing GLP-1s in this patient population, citing the lack of sufficient data in its Journal of Ethics. Others agreed.

The only data available so far came from a clinical trial (NCT04102189) of semaglutide plus lifestyle therapy for weight loss in 201 teens with obesity, followed for 68 weeks.

“We must be cautious in extrapolating potential long-term benefits and risks from adult data to youth,” Emma K. Edmondson, MD, MSHP and colleagues wrote, in an opinion piece about the pros and cons of GLP-1s in childhood obesity published in JAMA Pediatrics. Edmondson is a faculty member of the Department of Pediatrics at the Children’s Hospital of Philadelphia, Philadelphia.

Additionally, there are no data in support of any particular endpoint for weight-loss drug treatment, and several studies broadly suggest patients must be on the medications indefinitely, despite there being no prospective data on them in children.

“[I]t may be that adolescence is a particularly poor time to offer these medications because it is a period of rapid skeletal and brain development, because disordered eating may be more likely to emerge during this period, or because of other social-emotional aspects of adolescence,” Edmondson and colleagues wrote.

Other Drugs and Approaches

The FDA is currently evaluating a phase 3 clinical trial of the drug liraglutide for obesity treatment in children as young as age 6, which showed a mean BMI reduction of 5.8% in the trial group compared with 1.6% in the placebo group.

A combination of phentermine/topiramate plus lifestyle therapy was studied in a clinical trial (NCT03922945) of 110 teens with obesity and followed for 56 weeks.

Many studies of IHBLT by itself in childhood obesity have been done. One such study demonstrated that some nutritional and behavioral counseling in the pediatric clinical setting over 6 months helped patients stabilize their weight. Those given intensive levels of counseling actually lost weight and lowered their BMIs by month 6.

Inconsistent Access to Care

Although Wright and colleagues’ study found that nutritional counseling for children and adolescents with obesity also trended slightly upward on a monthly basis after the new AAP guidelines (OR, 1.01; 95% CI, 1.00-1.01), she said in an the interview that the 26-week protocols for the IHMLT courses are often difficult for patients to access, either because of lack of transportation or because they are not readily available in all communities, particularly in underserved communities where obesity is more prevalent.

“In our region, which includes at least two dedicated children’s hospitals, we are not aware of any programs offering this intensity of services,” Edmondson and colleagues wrote.

“In addition, less intensive but more available options, for example through interdisciplinary weight management clinics, [also] are often difficult for families to access,” Edmondson and her colleagues wrote.

Not All Obesity the Same

There have been efforts to refine the understanding of childhood obesity, such as the Lancet Diabetes & Endocrinology “Definition and Diagnostic Criteria of Obesity”, which includes the pediatric population.

The consensus statement calls for additional metrics beyond BMI to confirm excess adiposity, such as waist circumference or bioelectrical impedance, but a recent perspective published in Pediatrics claims these are not useful since using the “raw BMI values, except for a BMI 40 kg/m² or greater, for which excess adiposity may be assumed, ignores the normal BMI changes across a child’s growth and development.” 

The authors of the perspective also assert that the recommendations “such as waist circumference and bioelectrical impedance, are currently not standardized or validated across pediatric age groups.”

Prevention Over Intervention

Even without a refined understanding, Elaira Perrin, MD, Bloomberg Distinguished Professor of Primary Care at Johns Hopkins Schools of Medicine and Nursing in Baltimore believes prevention has potential across all levels of obesity. “I do think that some simple prevention ideas can be universal and support a lot of children,” she said.

Previously, as founder of Duke University’s Center for Childhood Obesity Research, Perrin also was part of a team that conducted a randomized clinical trial of a digital, low-literacy obesity prevention method for families of newborns. The results, published in JAMA, found that the infants in families who participated in the study group had lower weight-for-length trajectories over the first 24 months of life.

“We were able to reduce childhood obesity from ~13% to about 7% at age 2 years by starting to educate parents when infants were born,” Perrin said of the study.

Overall, Perrin said she believes in prevention over treatment, “But for the children who need treatment today, we should not delay. I think we always assume children will outgrow obesity, but, unfortunately, we know from a lot of research that obesity tends to worsen over time and certainly the health problems associated with obesity get worse over time.”

Wright and Perrin reported no conflicts of interest. Edmondson received an American Diabetes Association grant.

NICE has approved pembrolizumab with chemotherapy for advanced endometrial cancer, cutting death risk by 26% and it is now available on the NHS

NICE has approved a groundbreaking new treatment for advanced endometrial cancer, marking a significant shift in how the disease may be managed on the NHS. For the first time, patients will have access to an innovative combination therapy that offers new hope where options were once limited. This decision could change outcomes for thousands, offering a ray of hope in the fight against cancer and signalling a bold step forward in cancer care.

A UK-first combination therapy for endometrial cancer

Endometrial cancer is the most common gynecological cancer in the UK, with around 9,700 people diagnosed every year. Advanced endometrial cancer impacts life expectancy and quality of life, and only 15% of people diagnosed with stage 4 disease survive for five years or more.

This approval marks the first time immunotherapy has been combined with chemotherapy as a first-line treatment for patients with advanced endometrial cancer.

The treatment combines pembrolizumab, made by Merck Sharp & Dohme, with chemotherapy drugs carboplatin and paclitaxel. Pembrolizumab helps the immune system recognize and attack cancer cells, while chemotherapy damages these cells to stop them from growing and dividing. This combination approach leverages both the body’s immune system and conventional chemotherapy, resulting in better outcomes for individuals facing cancer.

Reduces death by 26%

Clinical trials have revealed that adding pembrolizumab to chemotherapy reduces the risk of death by 26% compared with chemotherapy alone. Trials also showed that adding the immunotherapy to chemotherapy can slow down cancer progression, offering people valuable additional time with improved quality of life.

Treatment is used for up to two years, or is stopped earlier if the cancer progresses or side effects worsen, allowing for personalised care based on patient response.

“For people with advanced endometrial cancer, this innovative combination offers a powerful new treatment option. It marks a major step forward, and we’re pleased to recommend it as part of our commitment to getting the best care to people, fast, while ensuring value for the taxpayer,” said Helen Knight, Director of Medicines Evaluation at NICE.

Dr Eleanor Jones, Chair of Trustees at Peaches Womb Cancer Trust, said: “We hope that this is just the first step towards wider availability of more effective first-line treatment options for everyone affected by womb cancer.”

“This additional treatment for primary advanced and recurrent mismatch repair proficient and deficient endometrial cancer will provide much-needed options for patients currently facing the reality of limited cancer treatments. Access to this innovative first-line treatment fills a significant unmet need.”

“Peaches Womb Cancer Trust has welcomed the opportunity to contribute to appraisals of pembrolizumab in both Scotland and England. We could not have done so without the contributions of Peaches Patient Voices, a group of people affected by womb cancer whose powerful testimonies and experiences informed our submissions.”

The treatment will be available immediately through the Cancer Drugs Fund, following a commercial arrangement between Merck Sharp & Dohme and the NHS that ensures cost-effectiveness while providing rapid access to this breakthrough therapy for eligible patients. This immediate availability brings hope to those in need of this treatment, signalling a new era in cancer care.

Just a few years ago, predicting how a string of amino acids assembled into a functional protein was one of biology’s most formidable puzzles. That was until artificial intelligence (AI) cracked the problem wide open, earning global acclaim and even last year’s Nobel prize in chemistry.

That breakthrough relied on deep learning, a form of AI that learns from massive datasets to make predictions, such as the shape of proteins. Now, researchers are building on that momentum with generative AI. A powerful new class of AI model that, rather than just predicting structure, can imagine entirely new possibilities – from unknown protein sequences to novel treatments for a wide range of diseases.

‘Most protein design work starts with a perfect, experimentally determined 3D map of the target,’ says Timothy Jenkins of the Technical University of Denmark. ‘But for many of the most important [therapeutic] targets … these maps simply don’t exist. This has been a major roadblock for personalised medicine.’

Jenkins and his collaborators recently published a study in which they used a generative AI model called RFdiffusion to design molecules that help the immune system recognise and attack cancer.¹ ‘Put simply, we created a new, ultra-fast pipeline for making precision cancer immunotherapies,’ he says.

Game changer for targeted therapies

The process works like a high-speed assembly line, with different AI tools handling different steps. ‘First we show RFdiffusion a 3D picture of the cancer flag we want to target,’ explains Jenkins. This 3D picture can come from experimental data or from AI-based structure prediction. ‘The AI then “dreams up” thousands of completely new, small protein shapes … that it thinks will fit perfectly onto that target,’ he adds.

A second AI model takes those shapes and figures out the exact amino acid sequences needed to build them. ‘This process is incredibly fast,’ says Jenkins. ‘Generating thousands of potential designs on a computer takes a matter of hours or days, whereas finding just one candidate using traditional lab methods can take months or even years.’

Molecular dynamics simulations are then used as a ‘virtual crash test’ to see how well the designed proteins stick to their cancer targets, helping the team narrow down candidates before moving to lab experiments.

‘The fact that we were able to create a successful binder based on a purely computational prediction is a game-changer,’ says Jenkins. ‘It demonstrates that our approach is not limited to the small number of well-characterised targets and can be extended to design therapies for truly personalised cancer targets, for which no structural information is available.’

Dreaming up proteins to kill deadly bacteria

Beyond personalised cancer therapy, a group led by Rhys Grinter at the University of Melbourne and Gavin Knott at Monash University are using generative AI to design proteins that kill antibiotic-resistant bacteria.²

‘AI-based protein design effectively enabled us to dream small proteins into existence that would bind ChuA,’ says Grinter. ChuA is an outer membrane transporter protein used by pathogenic bacteria Escherichia coli and Shigella to extract haem – a rich source of iron – from their hosts.

Using AlphaFold2, the team predicted the 3D structure of ChuA from its amino acid sequence in minutes. The model was then evaluated for accuracy, and a strategy was developed to block ChuA’s function. Generative AI tools, RFdiffusion and ProteinMPNN, were subsequently used to design proteins capable of interfering with the target.

‘The entire process took a few weeks, with a success rate of 10–50% for functional designs,’ says Knott. ‘This approach effectively shaves months to years off the standard experimental structural biology approach and rapidly accelerates development of novel biologics.’

‘It’s amazing and underscores the power and transformative potential of AI in protein design,’ adds Grinter.

Grinter, Knott, Jenkins and their colleagues favour AI platforms that are freely accessible to the wider scientific community. Making these tools available to all has helped lower barriers for researchers worldwide. As a result, a wider range of experts can collaborate and innovate, accelerating progress on pressing societal challenges such as antibiotic resistance and personalised cancer therapies.

‘However, it’s not as simple as point and click,’ says Knott. ‘At the moment, the technology still requires a deep understanding of protein structure and function relationships.’

And there is still a need for caution because, despite the impressive capabilities of generative AI, it has inherent limitations rooted in the data it learns from. ‘Generative AI is incredibly powerful, but it’s not magic,’ says Jenkins. ‘Models are trained on the thousands of protein structures we already know. If we ask them to design something radically different from anything they’ve “seen” before, they can sometimes “hallucinate” a design that looks good on the computer but isn’t physically stable or functional in the real world.’

‘Biology exists in the real world, so AI achieves real value when coupled with experimental techniques and applied to biological systems,’ concludes Grinter. ‘Combining experiments and AI has transformative power for scientific discovery and technology development. We think in the future that AI tools will form a central component of almost all aspects of biological research.’

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Weight loss and diabetes drugs on the market often do not achieve long-term weight loss for patients. GLP-1 drugs target brain neurons that control appetite but frequently cause side effects. Nausea and vomiting force 70% of patients to stop treatment within a year. Syracuse University chemistry professor Robert Doyle is leading a multidisciplinary team that has identified a different brain target for treating obesity and diabetes, potentially offering weight loss without gastrointestinal distress.

Neurons are the most well-known and obvious target in research and drug development for brain conditions. GLP-1 drugs, for example, target brain neurons in the hindbrain involved in appetite control. But researchers are looking beyond neurons to study “support” cells such as glia and astrocytes that could aid appetite reduction.

A collaborative research effort has revealed that support cells play a role in reducing feelings of hunger, although this process has not been studied in-depth.

“We wanted to know whether support cells might produce new peptides or new signaling molecules that might be critical in body weight reduction,” says Doyle, a medicinal chemist and the Jack and Laura H. Milton Professor of Chemistry in the College of Arts and Sciences at Syracuse University. Doyle is also a professor of pharmacology and medicine at SUNY Upstate Medical University.

Doyle and his research partners at the University of Pennsylvania and the University of Kentucky identified a chemical created by brain cells called astrocytes that could be key in designing future appetite control drugs without negative side effects. Their study appeared in Science Translational Medicine.

How it works

Think of each brain neuron as a light bulb and support cells as the components that allow the light bulb to brighten, including the wiring, switch and filament.

“All of those supporting parts beyond the light bulb play a role in making the light shine,” says Doyle.

The research team discovered that some support cells in the hindbrain naturally produce a molecule named octadecaneuropeptide (ODN), which suppresses appetite. In lab tests, injecting ODN directly into rats’ brains made them lose weight and improved how they processed glucose.

However, injecting directly into the brain isn’t a practical treatment for people, so researchers created a new version of the molecule named tridecaneuropeptide (TDN). This molecule version could be given to human patients through regular injections akin to today’s Ozempic or Zepbound. When tested in obese mice and musk shrews, TDN helped the animals lose weight and respond better to insulin without causing nausea or vomiting.

Marathon shortcut

One goal of the research team is to produce weight loss without aiming new therapeutic molecules at neurons. The new TDN molecule bypasses neurons, taking a shortcut to directly target neurons’ downstream support cells, which researchers found also produce appetite suppression. TDN cuts short the “marathon” of chemical reactions and negative side-effects caused by GLP-1 drugs.

“Instead of running a marathon from the very beginning like current drugs do, our targeting downstream pathways in support cells is like starting the race halfway through, reducing the unpleasant side effects many people experience,” says Doyle. “If we could hit that downstream process directly, then potentially we wouldn’t have to use GLP-1 drugs with their side effects. Or we could reduce their dose, improving the toleration of these drugs. We could trigger weight loss signals that happen later in the pathway more directly.”

A new company called CoronationBio has been launched to turn this discovery into a real-world treatment. The company has licensed intellectual property related to ODN derivatives for the treatment of obesity and cardio-metabolic disease from Syracuse University and the University of Pennsylvania, with a focus on translating candidates into the clinic. They’re now teaming up with other companies to develop this treatment and aim to start human trials in 2026 or 2027.

Reference: Geisler CE, Chichura KS, Orativskyi O, et al. Hindbrain octadecaneuropeptide gliotransmission as a therapeutic target for energy balance control without nausea or emesis. Sci Transl Med. 17(808):eadu6764. doi: 10.1126/scitranslmed.adu6764

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ATP citrate lyase (ACLY) is a central enzyme in metabolism, best known for its role in cholesterol and fatty acid synthesis. A validated target in cardiovascular disease, new research from Esperion Therapeutics suggests that ACLY could also play a role in liver disease – specifically, primary sclerosing cholangitis (PSC).

PSC is a rare, chronic cholestatic liver disorder with no approved treatments. Its aetiology remains unclear but is characterised by ongoing inflammation and fibrosis of the bile ducts, often progressing to liver failure. With limited therapeutic targets and high unmet need, PSC remains one of the most challenging conditions in hepatology.

Using large-scale genetic data, multiomic analysis and targeted preclinical studies, the team at Esperion is building a case for ACLY inhibition in PSC. The approach could offer a new angle on a disease that has thus far resisted most conventional drug development strategies.

At Esperion Therapeutics, the link between ACLY and liver disease did not emerge by chance. It was the result of a deliberate, data-driven investigation that began with established cholesterol biology and led into entirely new therapeutic territory.

“It’s been like a detective story,” says Stephen Pinkosky, Vice President of Drug Discovery and Early Development at Esperion. As with many such investigations, it began with a familiar target – ACLY – showing unexpected behaviour in a different disease.

From heart disease to liver inflammation

ACLY sits at the crossroads of sugar and fat metabolism, converting citrate into acetyl-CoA – a critical building block for lipid synthesis. Inhibiting ACLY has been shown to reduce LDL cholesterol (LDL-C) and lower cardiovascular risk. Esperion’s approved therapies are already based on this mechanism.

Yet something new was starting to surface. “Earlier work made clear that ACLY played a key role in cholesterol metabolism in a specific cell type in the liver,” Pinkosky explains. “Emerging evidence was indicating that the role of ACLY might be much broader but knowing where to focus was challenging.”

Rather than being confined to hepatocytes or lipid levels, dysregulated ACLY activity appeared to contribute to immune dysfunction, inflammation and fibrosis – all central to PSC.

Follow the data

How did a programme focused on cardiovascular metabolism come to uncover a potential role for ACLY in a complex liver disease like PSC?

“Working with our collaborator, we found that ACLY is causally associated with multiple clinical liver outcomes in a very broad population,” says Pinkosky. The insight came through phenome-wide association studies (PheWAS), which combine large genomic datasets with clinical outcomes to identify statistically significant genetic associations.

However, associations alone were not sufficient. To justify moving into a new disease area, the biology had to be traced from gene variant to disease process.

“Mechanistic investigations by our team and others had begun to support a role of ACLY in liver immune cells, inflammatory cells and fibroblasts. But rather than increasing LDL-C, ACLY dysregulation contributes to inflammation, fibrosis and immune dysfunction.”

Esperion needed more than correlation. They needed a detailed map of how ACLY interacted with liver disease processes.

Building a liver disease network from scratch

“No single existing dataset captures the complexity of liver disease well enough, so we built our own multilayer network using several multiomic datasets from patients with a common form of liver disease,” Pinkosky explains.

By integrating transcriptomic, proteomic and other multiomic data – and applying machine learning and AI – the team developed a systems-level model of liver disease. This approach allowed them not only to identify disrupted pathways, but also to understand how those pathways interact and contribute to disease progression.

“Creating a rank order of liver diseases in which ACLY could be important, we found that both chronic and immune forms of cholangitis were at the top,” he says.

PSC stood out immediately – both for its biology and the urgent unmet clinical need.

Designing drugs for a disease without a known cause

Esperion then began screening ACLY inhibitors for activity relevant to PSC. However, this was far from a typical hit-to-lead process, as the disease has no clear cause or universal biomarker, so it’s unclear which endpoints to prioritise.

“The cause of PSC is unknown, making it difficult to determine which drug effects to prioritise during discovery and optimisation,” says Pinkosky.

Rather than seeking a single causal mechanism, the team concentrated on addressing the downstream biological consequences. “Those datasets helped us to identify novel ACLY pathways that are dysregulated in patients with a common form of liver disease, but also relevant to PSC.”

Esperion’s compound screens were specifically designed to measure how candidates affected immune, inflammatory and fibrotic signalling. “We then built tests into our screening cascade that allowed us to design and validate compounds that appeared to improve the dysregulation in those pathways,” he says.

The models that matter

Even with compelling computational data and validated targets, demonstration of preclinical efficacy in biological systems was still required.

“Even though we had significant evidence from human genetics and multiomics that ACLY was a good target for liver disease, we still need to conduct interventional preclinical studies to test whether our inhibitors actually do what we designed them to do.”

“No single model captures all of the complicated processes that lead to liver disease in humans,” Pinkosky says. “So, we needed to use multiple models and understand the strengths and weaknesses of each when testing our potential drug candidates.”

In vivo studies showed reductions in inflammation, fibrosis and liver injury – key hallmarks of PSC. Equally encouraging were results from 3D human liver microtissues, which more closely reflect human disease.

“The human microtissue approach gave us confidence that these effects will be relevant in humans. This ability to address the injury, as well as the resulting inflammation and fibrosis, makes us optimistic about our findings,” Pinkosky asserts.

Not just a target

For Esperion, the ACLY programme is not only about targeting a single enzyme. It is about creating a discovery framework that integrates population-scale genetic data, computational modelling and translational biology to reduce the risks of early-stage development.

“What excites me about PheWAS and multiomics is that they can help to bridge the gap between preclinical models and patients,” reveals Pinkosky.

One key resource was the UK BioBank – a dataset of genomic and phenotypic information from over 500,000 individuals. “Applying PheWAS to that data revealed consistent associations of genetically predicted ACLY inhibition with significant reductions in the risk of liver disorders.

“Multiomics analyses took us even further, helping to validate existing disease pathways and identify new ones rather than hoping that preclinical models alone would get it right.”

“A unique game-changer”

If ACLY inhibition can successfully reduce inflammation, fibrosis and immune dysregulation in PSC, it may offer a fundamentally new approach to treating the disease.

“Complex diseases such as PSC almost invariably require multifaceted treatments, which is what we believe sets us apart,” says Pinkosky.

“By targeting ACLY – one pathway – we hope to achieve multiple cell-specific effects. Potentially, this will enable our drug candidate to address both the injury component of PSC and the resulting immune, inflammatory and fibrotic responses.

“In plain English, our goal is to stop the damage and to keep it from recurring: a unique game-changer.”

What comes next

Before clinical trials can begin, Esperion will complete a series of regulated preclinical safety studies and continue refining its understanding of ACLY’s role in PSC. The team is also focused on developing robust biomarkers to measure ACLY inhibition and its downstream effects in future trials.

“Our Esperion team is also focused on discovering and developing biomarkers, which will help us understand how well the drug is inhibiting ACLY in future clinical studies and whether it is having the expected downstream effects on PSC.

“There is much work left to be done,” says Pinkosky, “but we’re quite optimistic about where this effort will lead.”

What began as a simple case of suspected flu turned into a life-altering diagnosis for 26-year-old triathlete Kieran Shingler from Warrington, England. Initially experiencing what seemed like routine cold symptoms: a sore throat, runny nose, and persistent headache where Kieran believed he had seasonal flu or Covid-19. However, within weeks, his health rapidly deteriorated, leading to shocking medical discoveries. Doctors revealed he had an aggressive Grade 3 astrocytoma, a fast-growing malignant brain tumour, and gave him just one year to live. His journey highlights how easily life-threatening conditions can mimic common illnesses, delaying treatment.

How brain tumour symptoms mistaken for flu and covid-19

On Bonfire Night 2022, Kieran experienced mild symptoms: a sore throat, a runny nose, and a nagging headache. Like millions during that period, he suspected Covid-19 and tested himself multiple times. When all tests came back negative, he and his girlfriend, Abbie Henstock, assumed it was the flu. But this “flu” never went away. As reported, in the weeks that followed, Kieran’s condition deteriorated rapidly. He became fatigued, struggled to keep food down, and developed excruciating headaches—pain that was unusual even for flu or migraines.

“He was so fit—doing triathlons, working out almost every day—and then he suddenly couldn’t even eat without being sick. We knew something was seriously wrong,” Abbie recalled. Two weeks after his symptoms started, Kieran’s late mother, Lisa, noticed how badly he was struggling and contacted their family GP. Concerned about possible meningitis, the GP referred him to Warrington Hospital.At the hospital, doctors ran tests and performed a CT scan, which revealed a shocking discovery: there was a mass on Kieran’s brain. He was immediately blue-lighted to The Walton Centre in Liverpool, a specialist neurology facility.

Multiple surgeries and MRI scans uncover fast-growing malignant brain tumour

At The Walton Centre, an MRI scan confirmed a tumour was obstructing the flow of cerebrospinal fluid, which helps protect the brain and spinal cord. This blockage was causing dangerous intracranial pressure that could have proved fatal if not treated immediately.Doctors explained that surgery was necessary—not just to treat the tumour but also to relieve the fluid build-up in Kieran’s brain.

Kieran underwent an Endoscopic Third Ventriculostomy (ETV), a minimally invasive surgery designed to create a new pathway for fluid circulation and reduce pressure inside the brain. Initially, the surgery worked, and Kieran began to feel better. But this was only the start of a complex medical journey, as the tumour itself still needed to be addressed.

A few weeks later, doctors performed a craniotomy to remove as much of the tumour as safely possible and take samples for biopsy. While this surgery succeeded in reducing tumour size, it left Kieran with short-term memory loss, a common side effect when operating on critical brain regions. In December 2022, just one hour before his third surgery (to insert an external shunt after the ETV failed), doctors revealed the devastating biopsy results: Grade 3 Astrocytoma—a fast-growing, malignant brain tumour.

What is a Grade 3 Astrocytoma

Astrocytomas develop from astrocytes, star-shaped brain cells that support nerve function. Grade 3 tumours are:

These tumours often require multimodal treatment—surgery followed by radiotherapy and chemotherapy—but even then, they have a high recurrence rate. Doctors explained to Kieran’s family that such tumours are rarely curable and, in his case, he likely had only 12 months to live. To shield him from extra distress during the holidays, his family waited until after Christmas to tell him. “When I was finally told, I was scared and angry. I kept asking: why me?” Kieran said.

Radiotherapy brings hope as tumour reduces to 0.35 cm without ongoing treatment

In January 2023, Kieran began 30 sessions of radiotherapy alongside chemotherapy at The Clatterbridge Cancer Centre. This approach aimed to kill remaining tumour cells and slow its growth. The initial results were promising. By February 2023, MRI scans revealed the tumour was shrinking—a rare moment of relief for Kieran and Abbie amid months of uncertainty and fear. Unfortunately, by mid-2023, the tumour became resistant to the treatment and began growing again. Doctors switched to lomustine chemotherapy, which successfully reduced the tumour but caused liver damage, forcing doctors to stop treatment.Surprisingly, even without active treatment, Kieran’s tumour continued shrinking for 19 months, reducing from 5.5 cm to just 0.35 cm—an almost miraculous development.

Brain tumour returns in 2025 as Kieran turns to fundraising and alternative therapies

The respite didn’t last. In June 2025, a routine MRI revealed that the tumour was growing again. After years of fighting, three surgeries, multiple rounds of radiotherapy and chemotherapy, and temporary recovery, Kieran was once again facing the grim reality of a recurring, aggressive brain cancer. Determined to turn pain into purpose, Kieran and Abbie launched Kieran’s Krew, an online fundraising campaign. Initially intended to support brain cancer charities, it soon grew into a community-driven movement funding alternative therapies like:

To date, over £57,000 has been raised to support brain tumour charities and provide Kieran with therapies that improve his quality of life.“At every scan, we hoped for good news. Even when it was shrinking, we knew it could change at any time. Now we want to use our journey to help others,” Abbie explained. The brain tumour diagnosis profoundly changed Kieran’s life. Short-term memory loss, chronic pain, hospital visits, and emotional distress became part of daily life. Yet, Kieran remained determined to focus on positive moments, supported by family, friends, and the broader community that rallied around him.Also Read | 5 Ayurvedic habits to naturally heal and strengthen your liver function

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Researchers from the University of Birmingham have uncovered a completely new mechanism by which fat cells (adipocytes) control how they store and release fat.

Published today in Nature Chemical Biology, their study shows that a receptor previously known to respond to dietary fats can also work inside the cell, next to fat storage compartments called lipid droplets.

The results of the study change our understanding of how fat metabolism is regulated and could lead to new strategies in treating obesity, diabetes and other metabolic diseases.

The study is a collaboration with scientists at the Universities of Copenhagen, Glasgow and Montréal. The work was partially carried out at and supported by the Centre of Membrane Proteins and Receptors (COMPARE) and the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre.

“This discovery could change the way we think about drug development for metabolic diseases, offering more precise ways to regulate fat metabolism.”

Professor Davide Calebiro, Department of Metabolism and Systems Science, University of Birmingham.

Fat cells are specialised cells that store energy in the form of fat. When our body needs energy, fat cells release fatty acids in a process called lipolysis. Lipolysis is a delicate process; too much can lead to excess fat in the blood (a risk factor for diabetes and heart disease), while too little can make it difficult for the body to access stored energy.

Receptors like the one the researchers investigated (known as free fatty acid receptor 4 or FFA4), are part of the large family of G protein-coupled receptors (GPCRs). These receptors are found in cell membranes and play a crucial role in cell signalling. Traditionally, these receptors were thought to only be active on the cell surface, responding to signals from outside the cell.

However, the researchers found that FFA4 receptors are mainly located inside fat cells, on internal membranes near lipid droplets. When fat is broken down, the released fatty acids immediately activate these internal receptors. This triggers a local “brake” on fat breakdown, creating a fast, self-regulating feedback loop at each individual lipid droplet.

This ‘intracrine’ signalling (meaning the cell uses its own internally generated signal) is a completely new concept for metabolite-sensing receptors like FFA4.

Dr Shannon O’Brien, Research Fellow at the University of Birmingham, said: “We were surprised to find that FFA4 works like a built-in sensor inside fat cells, controlling fat breakdown in real time. This discovery reveals that fat cells have a highly localised way to control fat release, which could be crucial for maintaining healthy metabolism.”

Understanding this mechanism opens up new possibilities for designing innovative therapies that specifically target these intracellular FFA4 receptors. These treatments could help regulate fat storage and release in a more precise way, which could be particularly beneficial for people with metabolic diseases such as type 2 diabetes or obesity.

Davide Calebiro, Professor of Molecular Endocrinology at the University of Birmingham and senior author of the study, said: “This discovery not only describes a completely novel mechanism of ‘intracrine’ signalling, which could be relevant for other metabolically relevant receptors, but could also lead to the development of a new generation of more effective and better tolerated therapies for metabolic diseases.”

Reference: O’Brien SL, Tripp E, Barki N, et al. Intracrine FFA4 signaling controls lipolysis at lipid droplets. Nat Chem Biol. 2025. doi: 10.1038/s41589-025-01982-5

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