̽��ֱ�� of Cambridge - Medical Research Council

Throwing a ‘spanner in the works’ of our cells’ machinery could help fight cancer, fatty liver disease… and hair loss

cjb250 — Fri, 18 Apr 2025 18:00:53 +0000

Scientists at the Medical Research Council (MRC) Mitochondrial Biology Unit, ̽��ֱ�� of Cambridge, have worked out the structure of this machine and shown how it operates like the lock on a canal to transport pyruvate – a molecule generated in the body from the breakdown of sugars – into our mitochondria.

Known as the mitochondrial pyruvate carrier, this molecular machine was first proposed to exist in 1971, but it has taken until now for scientists to visualise its structure at the atomic scale using cryo-electron microscopy, a technique used to magnify an image of an object to around 165,000 times its real size. Details are published today in Science Advances.

Dr Sotiria Tavoulari, a Senior Research Associate from the ̽��ֱ�� of Cambridge, who first determined the composition of this molecular machine, said: “Sugars in our diet provide energy for our bodies to function. When they are broken down inside our cells they produce pyruvate, but to get the most out of this molecule it needs to be transferred inside the cell’s powerhouses, the mitochondria. There, it helps increase 15-fold the energy produced in the form of the cellular fuel ATP.”

Maximilian Sichrovsky, a PhD student at Hughes Hall and joint first author of the study, said: “Getting pyruvate into our mitochondria sounds straightforward, but until now we haven’t been able to understand the mechanism of how this process occurs. Using state-of-the-art cryo-electron microscopy, we’ve been able to show not only what this transporter looks like, but exactly how it works. It’s an extremely important process, and understanding it could lead to new treatments for a range of different conditions.”

Mitochondria are surrounded by two membranes. ̽��ֱ��outer one is porous, and pyruvate can easily pass through, but the inner membrane is impermeable to pyruvate. To transport pyruvate into the mitochondrion, first an outer ‘gate’ of the carrier opens, allowing pyruvate to enter the carrier. This gate then closes, and the inner gate opens, allowing the molecule to pass through into the mitochondrion.

“It works like the locks on a canal but on the molecular scale,” said Professor Edmund Kunji from the MRC Mitochondrial Biology Unit, and a Fellow at Trinity Hall, Cambridge. “There, a gate opens at one end, allowing the boat to enter. It then closes and the gate at the opposite end opens to allow the boat smooth transit through.”

Because of its central role in controlling the way mitochondria operate to produce energy, this carrier is now recognised as a promising drug target for a range of conditions, including diabetes, fatty liver disease, Parkinson’s disease, specific cancers, and even hair loss.

Pyruvate is not the only energy source available to us. Our cells can also take their energy from fats stored in the body or from amino acids in proteins. Blocking the pyruvate carrier would force the body to look elsewhere for its fuel – creating opportunities to treat a number of diseases. In fatty liver disease, for example, blocking access to pyruvate entry into mitochondria could encourage the body to use potentially dangerous fat that has been stored in liver cells.

Likewise, there are certain tumour cells that rely on pyruvate metabolism, such as in some types of prostate cancer. These cancers tend to be very ‘hungry’, producing excess pyruvate transport carriers to ensure they can feed more. Blocking the carrier could then starve these cancer cells of the energy they need to survive, killing them.

Previous studies have also suggested that inhibiting the mitochondrial pyruvate carrier may reverse hair loss. Activation of human follicle cells, which are responsible for hair growth, relies on metabolism and, in particular, the generation of lactate. When the mitochondrial pyruvate carrier is blocked from entering the mitochondria in these cells, it is instead converted to lactate.

Professor Kunji said: “Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions. Electron microscopy allows us to visualise exactly how these drugs bind inside the carrier to jam it – a spanner in the works, you could say. This creates new opportunities for structure-based drug design in order to develop better, more targeted drugs. This will be a real game changer.”

̽��ֱ��research was supported by the Medical Research Council and was a collaboration with the groups of Professors Vanessa Leone at the Medical College of Wisconsin, Lucy Forrest at the National Institutes of Health, and Jan Steyaert at the Free ̽��ֱ�� of Brussels.

Reference

Sichrovsky, M, Lacabanne, D, Ruprecht, JJ & Rana, JJ et al. Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier. Sci Adv; 18 Apr 2025; DOI: 10.1126/sciadv.adw1489

Fifty years since its discovery, scientists have finally worked out how a molecular machine found in mitochondria, the ‘powerhouses’ of our cells, allows us to make the fuel we need from sugars, a process vital to all life on Earth.

Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions

Edmund Kunji

bob_bosewell (Getty Images)

Bald young man, front view

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Powerful new MRI scans enable life-changing surgery in first for adults with epilepsy

cjb250 — Fri, 21 Mar 2025 00:01:25 +0000

Scientists have developed a new technique that has enabled ultra-powerful MRI scanners to identify tiny differences in patients’ brains that cause treatment-resistant epilepsy. It has allowed doctors at Addenbrooke’s Hospital, Cambridge, to offer the patients surgery to cure their condition.

Cambridge and London hospitals to pioneer brain implants to combat alcohol and opioid addiction

cjb250 — Mon, 17 Mar 2025 08:00:50 +0000

̽��ֱ��technique – known as deep brain stimulation – is to be trialled at Addenbrooke’s Hospital, Cambridge, and King’s College Hospital, London. ̽��ֱ��team behind the Brain-PACER: Brain Pacemaker Addiction Control to End Relapse study will soon be recruiting individuals with severe alcohol or opioid addiction who are interested in taking part.

Deep brain stimulation (DBS) is a neurosurgical procedure that delivers ongoing stimulation to the brain. DBS acts as a brain pacemaker to normalise abnormal brain activity. It is well-tolerated, effective and widely used for neurological disorders and obsessive compulsive disorder.

Although there have been several proof-of-concept studies that suggest DBS is effective in addictions, Brain-PACER – a collaboration between the ̽��ֱ�� of Cambridge, Kings College London and the ̽��ֱ�� of Oxford – is the first major, multicentre study to use DBS to treat craving and relapse in severe addiction.

Chief Investigator Professor Valerie Voon, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, said: “While many people who experience alcohol or drug addiction can, with the right support, control their impulses, for some people, their addiction is so severe that no treatments are effective. Their addiction is hugely harmful to their health and wellbeing, to their relationships and their everyday lives.

“Initial evidence suggests that deep brain stimulation may be able to help these individuals manage their conditions. We’ve seen how effective it can be for other neurological disorders from Parkinson’s to OCD to depression. We want to see if it can also transform the lives of people with intractable alcohol and opioid addiction.”

̽��ֱ��primary aim of the Brain-PACER study is to assess the effects of DBS to treat alcohol and opioid addiction in a randomised controlled trial study. Its mission is twofold: to develop effective treatments for addiction and to understand the brain mechanisms that drive addiction disorders.

DBS is a neurosurgical treatment that involves implanting a slender electrode in the brain and a pacemaker under general anaesthesia. These electrodes deliver electrical impulses to modulate neural activity, which can help alleviate symptoms of various neurological and psychiatric disorders.

Keyoumars Ashkan, Professor of Neurosurgery at King’s College Hospital and the lead surgeon for the study, said: “Deep brain stimulation is a powerful surgical technique that can transform lives. It will be a major leap forward if we can show efficacy in this very difficult disease with huge burden to the patients and society.”

During surgery, thin electrodes are carefully placed in precise locations of the brain. These locations are chosen based on the condition being treated. For addiction, the electrodes are placed in areas involved in reward, motivation, and decision-making.

Harry Bulstrode, Honorary Consultant Neurosurgeon at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and Clinical Lecturer at the ̽��ֱ�� of Cambridge, said: "We see first-hand how deep brain stimulation surgery can be life-changing for patients with movement disorders such as Parkinson’s disease and essential tremor. Thanks to this trial, I am now hopeful that we can help patients and their families – who have often struggled for years – by targeting the parts of the brain linked to addiction."

Dr David Okai, Visiting Senior Lecturer from the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, added: “DBS is safe, reversible and adjustable, so it offers a flexible option for managing chronic conditions. We hope it will offer a lifeline to help improve the quality of life for patients whose treatment until now has been unsuccessful.”

Details on the trial, including criteria for participation, can be found on the Brain-PACER website.

̽��ֱ��research is supported by the Medical Research Council, UK Research & Innovation.

People suffering from severe alcohol and opioid addiction are to be offered a revolutionary new technique involving planting electrodes in the brain to modulate brain activity and cravings and improve self-control.

We’ve seen how effective deep brain stimulation can be for neurological disorders from Parkinson’s to OCD to depression. We want to see if it can also transform the lives of people with intractable alcohol and opioid addiction

Valerie Voon

Shamir R, Noecker A and McIntyre C

Graphic demonstrating deep brain stimulation

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Map of brain’s appetite centre could enable new treatments for obesity and diabetes

Anonymous — Wed, 05 Feb 2025 16:00:15 +0000

Published today in Nature, this comprehensive resource, called HYPOMAP, provides an unparalleled view of the brain’s appetite centre and promises to accelerate the development of treatments for obesity and type 2 diabetes.

̽��ֱ��hypothalamus is often described as the brain’s ‘control centre’, orchestrating many of the body’s most vital processes. While much of our knowledge of the hypothalamus comes from animal studies, especially in mice, translating these findings to humans has long been a challenge. HYPOMAP bridges this gap by providing an atlas of the individual cells within the human hypothalamus. This resource not only charts over 450 unique cell types but also highlights key differences between the human and mouse hypothalamus — differences that have major implications for drug development.

“This is a game-changer for understanding the human hypothalamus,” said Professor Giles Yeo, senior author of the study from the Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL) and MRC Metabolic Diseases Unit, ̽��ֱ�� of Cambridge.

“HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity. It gives us a roadmap to develop more effective, human-specific therapies.”

Together with researchers at the Max Planck Institute for Metabolism Research in Cologne, Professor Yeo and colleagues used cutting-edge technologies to analyse over 400,000 cells from 18 human donors. HYPOMAP allows researchers to pinpoint specific cell types, understand their genetic profiles, and explore how they interact with neighbouring cells. This detailed cellular resolution offers invaluable insights into the circuits that regulate appetite and energy balance, as well as other functions such as sleep and stress responses.

Comparison with a mouse hypothalamus atlas revealed both similarities and critical differences. Notably, some neurons in the mouse hypothalamus have receptors for GLP-1 — targets of popular weight-loss drugs like semaglutide — that are absent in humans.

"While drugs like semaglutide have shown success in treating obesity, newer therapies target multiple receptors such as GLP-1R and GIPR. Understanding how these receptors function specifically in the human hypothalamus is now crucial for designing safer and more effective treatments," said Dr Georgina Dowsett from the Max Planck Institute for Metabolism Research and formerly at the IMS-MRL.

“Our map of the human hypothalamus is an essential tool for basic and translational research,” added Professor Jens C. Brüning, Director at the Max Planck Institute. “It allows us to pinpoint which mouse nerve cells are most comparable to human cells, enabling more targeted preclinical studies.”

HYPOMAP’s open-access nature ensures that it will be an invaluable resource for scientists worldwide. By offering insights into the hypothalamus’s role in conditions ranging from obesity to cachexia (a wasting condition associated with several illness, which involves extreme loss of muscle and fat), it provides a foundation for tackling some of the most pressing health challenges of our time.

Dr John Tadross, Consultant Pathologist at Addenbrooke’s Hospital and lead author from IMS-MRL, said: “This is just the beginning. ̽��ֱ��atlas itself is a milestone, but what could really make a difference for patients is understanding how the hypothalamus changes in people who are overweight or underweight. This could fundamentally shift our approach to metabolic health and enable more personalised therapies.”

With HYPOMAP, researchers have a new tool to unlock the secrets of the human brain’s metabolic control centre. By better understanding the human hypothalamus, science takes a significant step toward combating obesity, type 2 diabetes, and related conditions.

Reference
Tadross, JA, Steuernagel, L & Dowsett, GKC et al. A comprehensive spatio-cellular map of the human hypothalamus. Nature; 5 Feb 2025; DOI: 10.1038/s41586-024-08504-8

Adapted from a story by the Institute of Metabolic Science-Metabolic Research Laboratories and the Max Planck Institute for Metabolism Research

Scientists have created the most detailed map to date of the human hypothalamus, a crucial brain region that regulates body weight, appetite, sleep, and stress.

HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity

Giles Yeo

Sander Dalhuisen

Person holding burger bun with vegetables and meat

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Magnetic field applied to both sides of brain shows rapid improvement for depression

cjb250 — Mon, 28 Oct 2024 15:23:23 +0000

̽��ֱ��treatment – known as repetitive transcranial magnetic stimulation (TMS) – involves placing an electromagnetic coil against the scalp to relay a high-frequency magnetic field to the brain.

Around one in 20 adults is estimated to suffer from depression. Although treatments exist, such as anti-depressant medication and cognitive behavioural therapy (‘talking therapy’), they are ineffective for just under one in three patients.

One of the key characteristics of depression is under-activity of some regions (such as the dorsolateral prefrontal cortex) and over-activity of others (such as the orbitofrontal cortex (OFC)).

Repetitive transcranial magnetic stimulation applied to the left side of the dorsolateral prefrontal cortex (an area at the upper front area of the brain) is approved for treatment of depression in the UK by NICE and in the US by the FDA. It has previously been shown to lead to considerable improvements among patients after a course of 20 sessions, but because the sessions usually take place over 20-30 days, the treatment is not ideal for everyone, particularly in acute cases or where a person is suicidal.

In research published in Psychological Medicine, scientists from Cambridge, UK, and Guiyang, China, tested how effective an accelerated form of TMS is. In this approach, the treatment is given over 20 sessions, but with four sessions per day over a period of five consecutive days.

̽��ֱ��researchers also tested a ‘dual’ approach, whereby a magnetic field was additionally applied to the right-hand side of the OFC (which sits below the dorsolateral prefrontal cortex).

Seventy-five patients were recruited to the trial from the Second People’s Hospital of Guizhou Province in China. ̽��ֱ��severity of their depression was measured on a scale known as the Hamilton Rating Scale of Depression.

Participants were split randomly into three groups: a ‘dual’ group receiving TMS applied first to the right- and then to the left-hand sides of the brain; a ‘single’ group receiving sham TMS to the right-side followed by active TMS applied to the left-side; and a control group receiving a sham treatment to both sides. Each session lasted in total 22 minutes.

There was a significant improvement in scores assessed immediately after the final treatment in the dual treatment group compared to the other two groups. When the researchers looked for clinically-relevant responses – that is, where an individual’s score fell by at least 50% – they found that almost half (48%) of the patients in the dual treatment group saw such a reduction, compared to just under one in five (18%) in the single treatment group and fewer than one in 20 (4%) in the control group.

Four weeks later, around six in 10 participants in both the dual and single treatment groups (61% and 59% respectively) showed clinically relevant responses, compared to just over one in five (22%) in the control group.

Professor Valerie Voon from the Department of Psychiatry at the ̽��ֱ�� of Cambridge, who led the UK side of the study, said: “Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression. This means it could be particularly useful in severe cases of depression, including when someone is experiencing suicidal thoughts. It may also help people be discharged from hospital more rapidly or even avoid admission in the first place.

“ ̽��ֱ��treatment works faster because, by targeting two areas of the brain implicated in depression, we’re effectively correcting imbalances in two import processes, getting brain regions ‘talking’ to each other correctly.”

̽��ֱ��treatment was most effective in those patients who at the start of the trial showed greater connectivity between the OFC and the thalamus (an area in the middle of the brain responsible for, among other things, regulation of consciousness, sleep, and alertness). ̽��ֱ��OFC is important for helping us make decisions, particularly in choosing rewards and avoiding punishment. Its over-activity in depression, particularly in relation to its role in anti-reward or punishment, might help explain why people with depression show a bias towards negative expectations and ruminations.

Dr Yanping Shu from the Guizhou Mental Health Centre, Guiyang, China, said: “This new treatment has demonstrated a more pronounced – and faster – improvement in response rates for patients with major depressive disorder. It represents a significant step forward in improving outcomes, enabling rapid discharge from hospitals for individuals with treatment-resistant depression, and we are hopeful it will lead to new possibilities in mental health care.”

Dr Hailun Cui from Fudan ̽��ֱ��, a PhD student in Professor Voon’s lab at the time of the study, added: “ ̽��ֱ��management of treatment-resistant depression remains one of the most challenging areas in mental health care. These patients often fail to respond to standard treatments, including medication and psychotherapy, leaving them in a prolonged state of severe distress, functional impairment, and increased risk of suicide.

“This new TMS approach offers a beacon of hope in this difficult landscape. Patients frequently reported experiencing ‘lighter and brighter’ feelings as early as the second day of treatment. ̽��ֱ��rapid improvements, coupled with a higher response rate that could benefit a broader depressed population, mark a significant breakthrough in the field.”

Just under a half (48%) of participants in the dual treatment group reported local pain where the dual treatment was applied, compared to just under one in 10 (9%) of participants in the single treatment group. However, despite this, there were no dropouts.

For some individuals, this treatment may be sufficient, but for others ‘maintenance therapy’ may be necessary, with an additional day session if their symptoms appear to be worsening over time. It may also be possible to re-administer standard therapy as patients can then become more able to engage in psychotherapy. Other options include using transcranial direct current stimulation, a non-invasive form of stimulation using weak electrical impulses that can be delivered at home.

̽��ֱ��researchers are now exploring exactly which part of the orbitofrontal cortex is most effective to target and for which types of depression.

̽��ֱ��research was supported by in the UK by the Medical Research Council and by the National Institute for Health and Care Research Cambridge Biomedical Research Centre.*

Reference
Cui, H, Ding, H & Hu, L et al. A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study. Psychological Medicine; 23 Oct 2024; DOI: 10.1017/S0033291724002289

*A full list of funders is available in the journal paper.

A type of therapy that involves applying a magnetic field to both sides of the brain has been shown to be effective at rapidly treating depression in patients for whom standard treatments have been ineffective.

Our accelerated approach means we can do all of the sessions in just five days, rapidly reducing an individual’s symptoms of depression

Valerie Voon

TheDigitalArtist

Digital image of a brain

Yes

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Public Domain

Monoclonal antibodies offer hope for tackling antimicrobial resistance

cjb250 — Mon, 16 Sep 2024 10:31:11 +0000

A team lead by researchers at the ̽��ֱ�� of Cambridge has developed a monoclonal antibody drug, using a technique involving genetically engineered mice, that may help prevent infection from Acinetobacter baumannii, a bacteria associated with hospital-acquired infections, which is particularly common in Asia.

A. baumannii bacteria can cause life-threatening respiratory illness and sepsis in vulnerable individuals, particularly in newborn babies whose immune systems have not fully developed. It is usually spread through contaminated surfaces, medical equipment and via contact with others. In recent years infections with strains of this bacteria that are resistant to almost every antibiotic available have become common.

Professor Stephen Baker from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the ̽��ֱ�� of Cambridge said “A. baumannii is good at sticking to medical equipment, and if people are vulnerable or don't have a particularly well-developed immune system, they can succumb to this infection and get aggressive pneumonia requiring ventilation – and in many cases, the patients can acquire the infection from the ventilation itself.

“ ̽��ֱ��bacteria are naturally resistant to many antimicrobials, but as they’re now found in hospitals, they’ve acquired resistance to almost everything we can use. In some hospitals in Asia, where the infections are most common, there isn't a single antibiotic that will work against them. They’ve become impossible to treat.”

In a study published today in Nature Communications, the team produced monoclonal antibodies using transgenic mice – mice that have been genetically-engineered to have a human-like immune system, producing human antibodies instead of mouse antibodies. They went on to show that these monoclonal antibodies were able prevent infection with A. baumannii derived from clinical samples.

Monoclonal antibodies are a growing area of medicine, commonly used to treat conditions including cancer (for example, Herceptin for treating some breast cancers) and autoimmune disease (for example, Humira for treating rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis).

Usually, monoclonal antibodies are developed from the antibodies of patients who have recovered from an infection, or they are designed to recognise and target a particular antigen. For example, monoclonal antibodies targeting the ‘spike protein’ of the SARS-CoV-2 coronavirus were explored as a way of treating COVID-19.

In the approach taken by the Cambridge team, however, transgenic mice were exposed to the outer membrane of A. baumannii bacteria, triggering an immune response. ̽��ֱ��researchers then isolated almost 300 different antibodies and tested which of these was the most effective at recognising live bacteria, identifying the single monoclonal antibody mAb1416 as the best.

Professor Baker said: “Using this method, we don't infect the mice with the live bacteria, but we instead immunise them using multiple different elements and let the mouse’s immune system work out which ones to develop antibodies against. Because these mice have ‘humanised’ immune systems, we wouldn’t then need to reengineer the antibodies to work in humans.”

̽��ֱ��team treated mice with mAb1416, and 24 hours later exposed them to A. baumannii isolated from a child with sepsis in an intensive care unit. They found that those mice treated with the drug saw a significant reduction in bacterial load in their lungs a further 24 hours later, compared to mice that were not treated.

All of the isolates used to produce and test the monoclonal antibodies were from patients in Ho Chi Minh City, Vietnam, but the isolate used to test mAb1416 was taken from a patient ten years later than the other isolates. This is important because it shows that mAb1416 was protective against A. baumannii bacteria that may have evolved over time.

Professor Baker said: “Using this technique, you can take any bacterial antigen or cocktail of antigens, rather than waiting for somebody that's recovered from a particular infection – who you assume has developed an appropriate antibody response – give it to the mice and extract the antibodies you think are the most important.”

More work is now needed to understand the mechanism by which mAb1416 protects against infection, as this could allow the team to develop an even more effective treatment. Any potential new drug will then need to be tested in safety trials in animals before being trialled in patients.

Professor Baker added: “We know that monoclonal antibodies are safe and that they work, and the technology exists to produce them – what we have done is identify how to hit bacteria with them. Apart from the cost effectiveness, there's no reason why this couldn’t become a medicine within a few years. Given the emergency presented by antimicrobial resistance, this could become a powerful new weapon to fight back.”

̽��ֱ��research was funded by the Bill & Melinda Gates Foundation, the UK Medical Research Council Newton Fund, the Viet Nam Ministry of Science and Technology, and Wellcome.

Professor Baker is a fellow at Wolfson College, Cambridge.

Reference
Baker, S, Krishna, A & Higham, S. Exploiting human immune repertoire transgenic mice to identify protective monoclonal antibodies against an extensively antimicrobial resistant nosocomial bacterial pathogen. Nat Comms; 12 Sept 2024; DOI: 10.1038/s41467-024-52357-8

Monoclonal antibodies – treatments developed by cloning a cell that makes an antibody – could help provide an answer to the growing problem of antimicrobial resistance, say scientists.

We know that monoclonal antibodies are safe and that they work, and the technology exists to produce them – what we have done is identify how to hit bacteria with them

Stephen Baker

TopMicrobialStock (Getty Images)

A Petri dish with a culture of the Superbug Acinetobacter baumannii next to antibiotics

Yes

Children switch to walking and cycling to school after introduction of London’s Ultra-Low Emission Zone

cjb250 — Wed, 04 Sep 2024 23:01:29 +0000

Car travel contributes to air pollution, a major cause of heart and lung diseases including asthma attacks. Beyond this, it limits children's opportunities for physical activity, hindering their development and mental health, and increasing their risk of obesity and chronic illnesses.

Despite UK guidelines recommending a daily average of 60 minutes of moderate-to-vigorous physical activity for school-aged children and adolescents, less than half (45%) of children aged 5-16 met these levels in 2021. One in three children aged 10-11 in the UK are overweight or obese.

In April 2019, London introduced the ULEZ to help improve air quality by reducing the number of vehicles on the road that do not meet emissions standards. According to Transport for London, the central London ULEZ reduced harmful nitrogen oxides by 35% and particulate matter by 15% in central London within the first 10 months of its introduction.

In a study published on 5 September in the International Journal of Behavioral Nutrition and Physical Activity, a team led by researchers at the ̽��ֱ�� of Cambridge and Queen Mary ̽��ֱ�� of London examined the impact of the ULEZ on how children travelled to school. ̽��ֱ��research was part of the CHILL study (Children’s Health in London and Luton).

̽��ֱ��study examined data from almost 2,000 children aged 6 to 9 years attending 84 primary schools in London and the control area, Luton. 44 schools were located with catchment areas within or bordering London’s ULEZ, and these were compared to a similar number in Luton and Dunstable (acting as a comparison group). ̽��ֱ��inclusion of the comparison site enabled the researchers to draw more robust conclusions and increased confidence in attributing the observed changes to the introduction of the ULEZ.

̽��ֱ��researchers collected data from the period June 2018 to April 2019, prior to ULEZ implementation, and again in the period June 2019 to March 2020, the year after implementation of the ULEZ but prior to COVID-19-related school closures.

Among those children in London who travelled by car prior to the introduction of the ULEZ, 4 in 10 (42%) switched to active modes, while one in 20 (5%) switched from active to inactive modes.

In contrast, only one in 5 (20%) children in Luton swapped from car travel to active modes, while a similar number (21%) switched from active to car travel. This means that children in London within the ULEZ were 3.6 times as likely to shift from travelling by car to active travel modes compared to those children in Luton and far less likely (0.11 times) to switch to inactive modes.

̽��ֱ��impact of the ULEZ on switching to active travel modes was strongest for those children living more than half a mile (0.78km) from school. This was probably because many children who live closer to school already walked or cycled to school prior to the ULEZ and therefore there was more potential for change in those living further away from their school.

̽��ֱ��study’s first author, Dr Christina Xiao from the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��introduction of the ULEZ was associated with positive changes in how children travelled to school, with a much larger number of children moving from inactive to active modes of transport in London than in Luton.

“Given children's heightened vulnerability to air pollution and the critical role of physical activity for their health and development, financial disincentives for car use could encourage healthier travel habits among this young population, even if they do not necessarily target them.”

Joint senior author Dr Jenna Panter from the MRC Epidemiology Unit, ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��previous Government was committed to increasing the share of children walking to school by 2025 and we hope the new Government will follow suit. Changing the way children travel to school can have significant effects on their levels of physical activity at the same time as bringing other co-benefits like improving congestion and air quality, as about a quarter of car trips during peak morning hours in London are made for school drop-offs.”

After ULEZ was introduced in Central London, the total number of vehicles on the roads fell by 9%, and by one-third (34%) for vehicles that failed to meet the required exhaust emission standards, with no clear evidence of traffic moving instead to nearby areas.

Joint senior author Professor Chris Griffiths from the Wolfson Institute of Population Health, Queen Mary ̽��ֱ�� of London, said: “Establishing healthy habits early is critical to healthy adulthood and the prevention of disabling long term illness, especially obesity and the crippling diseases associated with it. ̽��ֱ��robust design of our study, with Luton as a comparator area, strongly suggests the ULEZ is driving this switch to active travel. This is evidence that Clean Air Zone intervention programmes aimed at reducing air pollution have the potential to also improve overall public health by addressing key factors that contribute to illness.”

Due to the introduction of COVID-19 restrictions in late March 2020, the study was paused in 2020/2021 and results are only reported for the first year of follow-up. However, as both London and Luton, the study areas, were similarly affected, the researchers believe this disruption is unlikely to have affected the results. ̽��ֱ��study has restarted following up with the children to examine the longer-term impacts of the ULEZ. This will identify if the changes they observed in the year following the introduction of the ULEZ persist.

̽��ֱ��study was conducted in collaboration with Queen Mary ̽��ֱ�� of London, Imperial College, ̽��ֱ�� of Bedfordshire, ̽��ֱ�� of Edinburgh, ̽��ֱ�� of Oxford and ̽��ֱ�� of Southern California and funded by the National Institute for Health and Care Research Public Health Research (NIHR), NIHR Applied Research Collaboration North Thames, and Cambridge Trust.

Reference
Xiao, C et al. Children’s Health in London and Luton (CHILL) cohort: A 12-month natural experimental study of the effects of the Ultra Low Emission Zone on children’s travel to school. IJBNPA; 5 Sept 2024; DOI: 10.1186/s12966-024-01621-7

Four in ten children in Central London who travelled to school by car switched to more active modes of transport, such as walking, cycling, or public transport, following the introduction of the Ultra-Low Emission Zone (ULEZ), according to new research. In the comparison area with no ULEZ, Luton, only two in ten children made this switch over the same period.

Changing the way children travel to school can have significant effects on their levels of physical activity at the same time as bringing other co-benefits like improving congestion and air quality

Jenna Panter

Matt Brown

ULEZ signs (cropped)

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Anti-inflammatory drug could reduce future heart attack risk

Anonymous — Mon, 02 Sep 2024 10:52:31 +0000

A cancer drug that unlocks the anti-inflammatory power of the immune system could help to reduce the risk of future heart attacks, according to research part-funded by the British Heart Foundation. By repurposing an existing drug, researchers hope it could soon become part of routine treatment for patients after a heart attack.

̽��ֱ��findings will be presented at the European Society of Cardiology Congress in London by Dr Rouchelle Sriranjan, NIHR Clinical Lecturer in Cardiology at the ̽��ֱ�� of Cambridge.

High levels of inflammation in blood vessels are linked to an increased risk of heart disease and heart attacks. After a heart attack, the body’s immune response can aggravate existing inflammation, causing more harm and increasing risk even further. However, NICE guidelines don’t currently recommend the use of any anti-inflammatory drugs to reduce future risk.

Now, a team of researchers, led by Dr Joseph Cheriyan from Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, have found that low doses of an anti-inflammatory drug called aldesleukin, injected under the skin of patients after a heart attack, significantly reduces inflammation in arteries.

̽��ֱ��researchers are currently following up patients to investigate the longer-term impact of this fall in inflammation. To date, in the two and a half years after their treatment, there have been no major adverse cardiac events in the group that received aldesleukin, compared to seven in the group that received the placebo.

Professor Ziad Mallat, BHF Professor of Cardiovascular Medicine at the ̽��ֱ�� of Cambridge who developed the trial, said: “We associate inflammation with healing – an inbuilt response that protects us from infection and injury. But it’s now clear that inflammation is a culprit in many cardiovascular conditions.

“Early signs from our ongoing trial suggest that people treated with aldesleukin may have better long-term outcomes, including fewer heart attacks. If these findings are repeated in a larger trial, we’re hopeful that aldesleukin could become part of routine care after a heart attack within five to 10 years.”

Aldesleukin is already used to treat kidney cancer, as high doses stimulate the immune system to attack cancer cells. ̽��ֱ��Cambridge team previously found that doses one thousand times lower than those used in cancer treatment increased the number of regulatory T cells – a type of anti-inflammatory white blood cell – in patients’ blood compared to a placebo.

In the current trial at Addenbrooke's and Royal Papworth hospitals in Cambridge, 60 patients admitted to hospital with a heart attack or unstable angina received either low dose aldesleukin or placebo. Patients received an injection once a day for the first five days, then once per week over the next seven weeks. Neither the participants nor their doctors knew whether they had received the drug or placebo.

At the end of treatment, Positron Emission Tomography (PET) scans showed that inflammation in the artery involved in patients’ heart attack or angina was significantly lower in the group treated with aldesleukin, compared to those who received the placebo.

̽��ֱ��anti-inflammatory effect of aldesleukin appeared even more striking in the most inflamed arteries, leading to a larger reduction in inflammation levels in these vessels and a bigger difference between the two groups by the end of the study.

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist said: “Thanks to research, we have an array of effective treatments to help people avoid heart attacks and strokes and save lives. But, even after successful heart attack treatment, unwanted inflammation in the coronary arteries can remain, which can lead to life-threatening complications.

“A treatment to reduce inflammation after a heart attack could be a game-changer. It would help doctors to interrupt the dangerous feedback loop that exacerbates inflammation and drives up risk. This research is an important step towards that treatment becoming a reality.”

̽��ֱ��study was predominantly funded by the Medical Research Council, with significant support from the BHF and National Institute for Health and Care Research Cambridge Biomedical Research Centre (NIHR-BRC).

Originally published by the British Heart Foundation.

Repurposed cancer drug helps to calm inflammation in arteries.

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