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Pretoria Company Aims to Lead SA in Making Key TB Drug Ingredients

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Source: Unsplash CC0

By Catherine Tomlinson

Though several South African companies are producing HIV and TB medicines, the active ingredients that go into these medicines are usually imported from India or China. Now, a local company is planning to break new ground by making the active ingredients for two important TB medicines in Pretoria. We zoom in on the company’s efforts and outline some of the obstacles to getting such local production off the ground.

South Africa has a relatively robust pharmaceutical sector. Approximately 60% of the medicines sold in South Africa are locally produced, according to Dr Senelisiwe Ntsele, writing in an opinion piece for the Department of Trade, Industry and Competition (dtic).

But most of the time we are not producing these medicines from scratch. In fact, like most countries in the world, we mostly import the ingredients that make the medicines work – commonly referred to as active pharmaceutical ingredients, or APIs. In addition to APIs, medicines contain other inactive substances that maintain their form and structure and assist in their delivery: such as binders, stabilisers, and disintegrants.

Around 98% of the APIs used in locally formulated medicines are imported and South Africa spends around R15 billion a year importing APIs, according to Ntsele.

Government has tried to address South Africa’s dependence on imported APIs as part of its broader strategy to bolster the local pharmaceutical industry, which is identified as a priority sector for investment in the country’s Industrial Policy Action Plan. Several government departments provide support to the local pharmaceutical sector, including for local establishment of API manufacturing capacity. These departments include the dtic, the Department of Science and Innovation (DSI), the Technology Innovation Agency (TIA), and the Industrial Development Corporation (IDC) – South Africa’s development finance instrument.

In a bid to reduce the country’s reliance on imported APIs, Ketlaphela – a state-owned API manufacturing company – was announced in 2012. The plan was that Ketlaphela would produce APIs used in HIV medicines, but after multiple setbacks the initiative never got off the ground. Spotlight reported on the history of Ketlaphela in more detail here.

Turning to the private sector

Less well known than Ketlaphela, are government’s efforts to support API manufacturing capacity in the private sector. One private company that has received such government support and seem set to start delivering is Pretoria-based Chemical Process Technologies Pharma (CPT Pharma) that was established in 2014.

CPT Pharma is a subsidiary of Chemical Process Technologies, a company with many years of experience in chemical manufacturing and synthesis, including manufacturing of APIs for animal medicines. Human medicines, CPT Pharma’s core business, have stricter production management and quality control standards than those for animal medicines.

Dr Hannes Malan, Managing Director of CPT Pharma, told Spotlight that the company has 14 APIs in its pipeline, with a strong focus on TB medicines.

CCPT Pharma is a subsidiary of Chemical Process Technologies. (Photo: Supplied)

In 2023, the company secured a license from USAID to produce API for rifapentine, a drug widely used for TB prevention, and in 2022 they secured a licence from the Medicines Patent Pool to produce API for molnupiravir, a treatment for COVID-19. Malan pointed out that these two licenses were agreed with organisations aiming to expand the presence of API manufacturers in Africa – unlike typical arrangements driven by pharmaceutical companies looking to secure their own supply chains.

“For all the other APIs that we’re working on [beyond molnupiravir and rifapentine], we’re either working on technical packs [technical information about the API] that were available in the public domain or technologies that we’ve developed ourselves,” said Malan.

“Our approach has always been to look at the molecules, look at the market value, look at the technology, and then see if there’s an opportunity for us to develop technology that allows us to produce these compounds cost competitively,” he said.

“We really believe that to be competitive and independent, you have to have your own technology. Doing a technology transfer from Big Pharma does not make you independent,” Malan added.

How to fund it all?

In 2017, the company completed a pilot plant for making APIs. Then in 2020 it received approval from the South African Health Products Regulatory Authority (SAHPRA) to produce APIs for human use. The plant was built for R50 million, funded jointly by the IDC, TIA, and CPT Pharma.

Malan said that that the IDC and TIA also supported trial runs to test CPT Pharma’s manufacturing processes and technology. These tests included several APIs in development, such as isoniazid, a drug commonly used to prevent and treat TB.

The company has also secured funding from several international donors. The Gates Foundation provided support to develop manufacturing technology for the anti-malarial drug amodiaquine, as well as tuberculosis medicines bedaquiline and pretomanid. GIZ, a German development agency involved in a European Union project to boost vaccine and health product production in Africa, supported the company’s work on molnupiravir and dolutegravir – a widely used HIV medicine. USAID and the DSI are supporting the company’s work on developing rifapentine API manufacturing capacity.

Most of this financial support has been in the form of grants.

Still building new plants

While CPT Pharma has secured local and international funding to help construct a pilot plant and to develop its API manufacturing technology and processes, Malan said more investment is needed to support the construction of two commercial-scale manufacturing facilities: an isoniazid API manufacturing plant and a multiple API manufacturing facility.

Construction of the isoniazid manufacturing plant has already commenced using existing land and infrastructure with support from the IDC, but it is short of around R20 million to complete it, said Malan.

Although the plant is not yet operational, he said a company has already expressed interest in buying CPT Pharma’s locally produced isoniazid API. This company, said Malan, is contracted to supply isoniazid to government. The plan is to initially supply the company with isoniazid API produced at its pilot plant

Malan said the commercial plant, when built, will be able to manufacture enough isoniazid API to supply around 60% of local demand.

Things are less far down the road with plans for a plant to produce multiple different APIs at commercial scale, and more work is needed to understand the financing requirements for this type of facility, said Malan. “We want to do a bankable study and a concept design for such a plant,” he said. Based on CPT Pharma’s own experience, published data, and the required complexity and capacity of the plant, Malan said it is estimated that construction for the multi-API plant will cost around US$100 million or R1.8 billion.

Plans to commercialise

Meanwhile, the company is moving forward with plans to commercialise isoniazid and rifapentine API from its pilot plant. Isoniazid and rifapentine is increasingly used together as TB preventive therapy.

“For rifapentine, our pilot plant is seen as the commercial plant,” said Malan. “At this stage, we can use the pilot facility and the pilot reactor to produce enough rifapentine to get into the market and to grow the market.” But in the long term he said the company hopes to transfer rifapentine manufacturing to a larger commercial plant.

The company is also planning to apply for World Health Organization (WHO) pre-qualification status for its rifapetine API. The goal is to conduct demonstration runs in the pilot plant by June 2025 and validate the WHO pre-qualification application in September 2025.

If achieved, WHO pre-qualification of CPT Pharma’s rifapetine API would show that the company’s APIs meet high-quality standards. It would also allow CPT Pharma to supply rifapentine API to companies producing medicines for the broader African market, for which a significant proportion of medicines are procured by donors requiring WHO PQ approval.

Note: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation. Spotlight is editorially independent – an independence that the editors guard jealously.  Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Categories : CancerTags : Leave a comment

PVA Glue Boosts Effects of an Advanced Radiotherapy Treatment

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Photo by National Cancer Institute on Unsplash

Treatment for more advanced and difficult-to-treat head and neck cancers can be improved with the addition of polyvinyl alcohol (PVA), the same ingredient used in children’s glue. Researchers found that combining PVA with a boron-containing compound, D-BPA, improved the effects of a type of radiation therapy for cancer, compared to currently clinically used drugs. The PVA made the drug more selective of tumour cells and prolonged drug retention, helping to spare healthy cells from unnecessary radiation damage.

Japan became the first country to approve boron neutron capture therapy (BNCT), a type of targeted radiotherapy for cancer, in 2020. Doctors administer a boron-containing drug to patients, which is designed to selectively accumulate in tumour cells. The patients are then exposed to low-energy neutrons, which react with the boron, destroying cancer cells without damaging healthy cells.

The advantages of BNCT are that it targets only boron-containing cells, meaning that damage to healthy cells is less compared to some other treatments. It has also been found to be effective against some more challenging and recurring cancers. However, because low-energy neutrons are quite weak, their use is limited to certain areas of the body. Currently, they are approved for head and neck cancers, which are nearer the surface. Their effectiveness also depends on both the level and retention of boron within tumour cells for the duration of the treatment.

In newly published research, special research student Kakeru Konarita and Associate Professor Takahiro Nomoto from the University of Tokyo found that adding PVA to the boron-containing compound greatly improved both its accumulation and retention in cancer cells.

“We discovered that PVA, which is used in liquid glue, dramatically improves the efficacy of a compound called D-BPA, that until now has been removed from drug ingredients because it was considered useless,” explained Nomoto.

Neither PVA nor D-BPA exhibit pharmacological activity when administered alone. However, combining these compounds resulted in remarkably elevated tumour accumulation, prolonged retention and potent therapeutic efficacy, even when compared with a clinically used drug.”

Currently, the chemical substance L-BPA is the only approved boron compound for BNCT. It accumulates well within cancer cells, but, depending on the location of the cancer, can also enter some healthy cells. This makes it unsuitable for treating certain tumours. D-BPA is the enantiomer of L-BPA, meaning that its molecular structure is the mirror image of L-BPA but it is otherwise chemically identical. D-BPA appealed to the researchers because it appears to be more selective of cancer cells. However, on its own it doesn’t accumulate, which is why it was considered useless.

The team previously found that mixing PVA with L-BPA improved its effectiveness. In this latest research, they combined PVA with D-BPA and were surprised to see even higher levels of boron accumulating and more prolonged retention.

“There are many demands in the development of drugs for cancer treatment and much recent research and development has focused on complex combinations of expensive molecules,” said Nomoto. “However, we are concerned that such methods, when put into practice, will be so expensive that only a limited number of patients will benefit. In this study, we aimed to develop a drug with a simple structure and high functionality at a low cost.”

Now the team is promoting joint industry-academia collaboration to further this research and hope to apply this achievement to the treatment of other challenging cancers.

Source: University of Tokyo

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T Cells could Ease Brain Injury after Cardiac Arrest

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Photo by Mat Napo on Unsplash

Despite improvements in CPR and ambulance response times, only about one in 10 people ultimately survive after out-of-hospital cardiac arrest (OHCA). Most patients hospitalised with OCHA die of brain injury, and no medications are currently available to prevent this outcome. A team led by researchers from Mass General Brigham found that immune cells may play a key role.

Using samples from patients who have had an OHCA, the team uncovered changes in immune cells just six hours after cardiac arrest that can predict brain recovery 30 days later. They pinpointed a particular population of cells that may provide protection against brain injury and a drug that can activate these cells, which they tested in preclinical models. Their results are published in Science Translational Medicine.

“Cardiac arrest outcomes are grim, but I am optimistic about jumping into this field of study because, theoretically, we can treat a patient at the moment injury happens,” said co-senior and corresponding author Edy Kim, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital. “Immunology is a super powerful way of providing treatment. Our understanding of immunology has revolutionised cancer treatment, and now we have the opportunity to apply the power of immunology to cardiac arrest.”

As a resident physician in the Brigham’s cardiac intensive care unit, Kim noticed that some cardiac arrest patients would have high levels of inflammation on their first night in the hospital and then rapidly improve. Other patients would continue to decline and eventually die. In order to understand why some patients survive and others do not, Kim and colleagues began to build a biobank – a repository of cryopreserved cells donated by patients with consent from their families just hours after their cardiac arrest.

The researchers used a technique known as single-cell transcriptomics to look at the activity of genes in every cell in these samples. They found that one cell population – known as diverse natural killer T (dNKT) cells – increased in patients who would have a favourable outcome and neurological recovery. The cells appeared to be playing a protective role in preventing brain injury.

To further test this, Kim and colleagues used a mouse model, treating mice after cardiac arrest with sulfatide lipid antigen, a drug that activates the protective NKT cells. They observed that the mice had improved neurological outcomes.

The researchers note that there are many limitations to mouse models, but making observations from human samples first could increase the likelihood of successfully translating their findings into intervention that can help patients. Further studies in preclinical models are needed, but their long-term goal is to continue to clinical trials in people to see if the same drug can offer protection against brain injury if given shortly after cardiac arrest.

“This represents a completely new approach, activating T cells to improve neurological outcomes after cardiac arrest,” said Kim. “And a fresh approach could lead to life-changing outcomes for patients.”

Source: Mass General Brigham

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An Internationally Standardised Set of Handgrip Strength Norms

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Photo by Nsey Benajah on Unsplash

Convenient, safe, and non-invasive, ‘handgrip strength’ is a reliable predictor for age-related disease and disability. Now, a groundbreaking study has created the world’s largest and most geographically comprehensive international norms for handgrip strength, enabling global peer-comparison, health screening and surveillance across the adult lifespan.

Published in The Journal of Sport and Health Science, the new norms are based on 100 unique observational studies representing 2.4 million adults aged 20 to 100+ years, from 69 countries (representing six of the seven continents, 17 of 22 United Nations’ geographical subregions, and 71% of the world’s population). The study was led by the University of South Australia and conducted in collaboration with 140 authors across the globe.

It is the first time that norms have been reported for handgrip strength across different age groups and sexes at the international level.

Handgrip strength, or isometric grip, is measured via a handgrip dynamometer which is gripped and squeezed to record the maximum force a person can produce over a few seconds. A person with low handgrip, or low muscle strength, has a higher risk of death from all causes and cardiovascular disease as well as a higher incidence of physical disability.

The new study has established a percentile framework that ranks strength. Adults below the 20th percentile are considered to have ‘low’ strength; those between 20-39th percentiles have ‘somewhat low’ strength; those in the 40-59th percentiles have ‘moderate’ strength; those in the 60-79th percentiles have ‘somewhat high’ strength; and those at or above the 80th percentile having ‘high’ strength.

Importantly, norms can be used to monitor healthy aging by examining changes in strength over time.

Finally, international benchmarks for comparison

Lead researcher Professor Grant Tomkinson says the new norms will help clinicians better identify people who may be at risk of poor health and in need of interventions.

“Muscle strength, which reflects the ability of the muscles to produce force maximally, is a powerful biomarker of current and future health,” Prof Tomkinson says. “A good general measure of overall muscle strength is how hard you can grip. Grip strength improves a little throughout early adulthood, peaks between age 30 and 39, and then drops off as people age, especially in late adulthood.

“By establishing international handgrip norms through a reference population, we can determine how well someone compares to their peers of the same age and sex, and quickly identify people who need intervention.

“But until now, there has been no international markers by which to compare or benchmark.

“Our research has established robust international norms that enable clinicians and exercise professionals to interpret and relate results in a percentile ranking. For example, adults below the 20th percentile are considered to have ‘low’ strength, those between 20-39th percentiles have ‘somewhat low’ strength, and so on as the scale progresses.

“So, what we have developed is an international guideline and benchmark that enables clinicians to compare and track muscle strength – and therefore potential health risks – across the adult lifespan.”

The new norms will enable standardised grip strength test results for cross- and within-country comparisons, to identify trends over time, monitor improvements and evaluate the effectiveness of implemented public health policies. They will also facilitate individual feedback, advice, and health interventions for those at risk.

Source: University of South Australia

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Gluten Free Diet Reduces Coeliac Symptoms – and ‘Good’ Gut Bacteria

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Photo by Mariana Kurnyk: https://www.pexels.com/photo/two-baked-breads-1756062/

A research team led by the University of Nottingham has used magnetic resonance imaging (MRI) to better understand the impact a gluten free diet has on people with coeliac disease, which could be the first step towards finding new ways of treating the condition.

The MARCO study – MAgnetic Resonance Imaging in COliac disease is published in Clinical Gastroenterology and Hepatology (CGH) (link connects to BioRxiv copy).

Coeliac disease is a chronic condition affecting around one person in every 100 in the general population. When people with coeliac disease eat gluten, which is found in pasta and bread, their immune system produces an abnormal reaction that inflames and damages the gut tissue and causes symptoms such as abdominal pain and bloating.

The only treatment is a life- long commitment to a gluten free diet, which helps recovery of the gut tissue but still leaves many patients with gastrointestinal symptoms.

Luca Marciani, Professor of Gastrointestinal Imaging at the University, led the study. He said: “Despite being a common chronic condition, we still don’t precisely know how coeliac disease affects the basic physiological functioning of the gut and how the gluten free diet treatment may further change this.

“We launched the MARCO study to try and address this issue, by using MRI along with gut microbiome analysis to give us new insights into how a gluten-free diet affects people with coeliac disease.”

The team recruited 36 people who had just been diagnosed with coeliac disease and 36 healthy volunteers to participate in the study. Images were taken of their guts with MRI, along with blood and stool samples. The patients then followed a gluten free diet for one year and came back to repeat the study. The healthy participants came back one year later too and repeated the study, but they did not follow any diet treatment.

The study found that the newly diagnosed patients with coeliac disease had more gut symptoms, more fluid in the small bowel and that the transit of food in the bowel was slower than in the healthy controls.

The microbiota (the ‘bugs’ living in the colon) of the patients showed higher levels of ‘bad bugs’ such as E.coli. After one year of a gluten free diet, gut symptoms, bowel water and gut transit improved in the patients, but without returning to normal values. But the gluten free diet also reduced some of the ‘good bugs’ in the microbiota, such as Bifidobacteria associated with reduced intake of starch and wheat nutrients, due to the different diet.

The patient study was conducted by Radiographer Dr Carolyn Costigan, from Nottingham University Hospitals, as part of her PhD studies at the University of Nottingham.

It was particularly interesting to see how the imaging results on gut function correlated with changes in the ‘bugs’ in the colon microbiota. The findings increase our understanding of gut function and physiology in coeliac disease and open the possibility of developing prebiotic treatments to reverse the negative impact of the gluten free diet on the microbiome.”

Luca Marciani, Professor of Gastrointestinal Imaging

Dr Frederick Warren from the Quadram Institute, which contributed to the research, said: “This study is the result of an exciting and innovative research collaboration bringing together medical imaging technology and gut microbiome analysis. We provide important insights which pave the way for future studies which may identify novel approaches to alleviate long-term symptoms in coeliac patients.”

Source: University of Nottingham

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Fire Breaks out at Netcare Pretoria East Hospital

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Source: CC0

A fire broke out yesterday, Thursday 5th December, at Netcare Pretoria East Hospital in Moreleta Park, prompting the evacuation of hundreds of patients. City of Tshwane firefighters promptly arrived on the scene, quickly getting the blaze under control. No injuries were reported.

Speaking to Newzroom Afrika, Netcare spokesperson Lynne O’Connor said that the fire was under control and with the Fire Marshal declaring that parts of the hospital to be safe, patients were being returned to their wards. As to the extent of damage and the cause, she said that “We know that the fire broke out somewhere near the theatre complex.”

As per the disaster management protocols, Netcare evacuated every single one of the approximately 200 patients in the hospital as soon as the alarm went off. The procedure was precautionary and none of the patients were harmed. O’Connor praised the swift response of the Tshwane emergency services. She said the cause of the fire was being investigated, and the extent of the damage would still need to be evaluated, News24 reports.

“We are grateful that everyone was brought to safety and sincerely apologise to the affected patients and their families for the inconvenience.”

Categories : Regenerative Medicine Skeletal SystemTags : Leave a comment

A Revolutionary Coral-inspired Material for Bone Repair

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(Left) An image of a 3D-printed material implanted in vivo for 4 weeks. The photo was taken using a scanning electron microscope. Credit: Dr Zhidao Xia.
(Right) A photo of coral. Credit: Jesus Cobaleda.

Researchers at Swansea University have developed a revolutionary bone graft substitute inspired by coral which not only promotes faster healing but dissolves naturally in the body after the repair is complete.

This groundbreaking research, led by Dr Zhidao Xia from Swansea University Medical School in collaboration with colleagues from the Faculty of Science and Engineering and several external partners, has been patented and published in the leading journal Bioactive Materials.

Bone defects caused by conditions like fractures, tumours, and non-healing injuries are one of the leading causes of disability worldwide. Traditionally, doctors use either a patient’s own bone (autograft) or donor bone (allograft) to fill these gaps. However, these methods come with challenges, including a limited supply, the risk of infection and ethical concerns.

By using advanced 3D-printing technology, the team have developed a biomimetic material that mimics the porous structure and chemical composition of coral-converted bone graft substitute, blending perfectly with human bone and offering several incredible benefits:

  • Rapid Healing – It helps new bone grow within just 2–4 weeks.
  • Complete Integration – The material naturally degrades within 6–12 months after enhanced regeneration, leaving behind only healthy bone.
  • Cost-Effective – Unlike natural coral or donor bone, this material is easy to produce in large quantities.

In preclinical in vivo studies, the material showed remarkable results: it fully repaired bone defects within 3–6 months and even triggered the formation of a new layer of strong, healthy cortical bone in 4 weeks.

Most synthetic bone graft substitutes currently on the market can’t match the performance of natural bone. They either take too long to dissolve, don’t integrate well, or cause side effects like inflammation. This new material overcomes these problems by closely mimicking natural bone in both structure and biological behaviour.

Dr Xia explained: “Our invention bridges the gap between synthetic substitutes and donor bone. We’ve shown that it’s possible to create a material that is safe, effective, and scalable to meet global demand. This could end the reliance on donor bone and tackle the ethical and supply issues in bone grafting.”

Innovations like this not only promise to improve patient quality of life but also reduce healthcare costs and provide new opportunities for the biomedical industry.

The Swansea University team is now looking to partner with companies and healthcare organisations to bring this life-changing technology to patients around the world.

Source: Swansea University

Categories : Cardiovascular Disease NeurologyTags : Leave a comment

The Heart has a ‘Brain’ of its Own

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Human heart. Credit: Scientific Animations CC4.0

New research from Karolinska Institutet and Columbia University shows that the heart has a mini-brain – its own nervous system that controls the heartbeat. A better understanding of this system, which is much more diverse and complex than previously thought, could lead to new treatments for heart diseases. The study, conducted on zebrafish, is published in Nature Communications.

The heart has long been thought to be controlled solely by the autonomic nervous system, which transmits signals from the brain. The heart’s neural network, which is embedded in the superficial layers of the heart wall, has been considered a simple structure that relays the signals from the brain. However, recent research suggests that it has a more advanced function than that.

Controlling the heartbeat

Scientists have now discovered that the heart has its own complex nervous system that is crucial to controlling its rhythm.

“This ‘little brain’ has a key role in maintaining and controlling the heartbeat, similar to how the brain regulates rhythmic functions such as locomotion and breathing,” explains Konstantinos Ampatzis, principal researcher and docent at the Department of Neuroscience, Karolinska Institutet, Sweden, who led the study.

The researchers identified several types of neurons in the heart that have different functions, including a small group of neurons with pacemaker properties. The finding challenges the current view on how the heartbeat is controlled, which may have clinical implications.

Surprising complexity revealed

“We were surprised to see how complex the nervous system within the heart is,” says Konstantinos Ampatzis. “Understanding this system better could lead to new insights into heart diseases and help develop new treatments for diseases such as arrhythmias.” 

The study was conducted on zebrafish, an animal model that exhibits strong similarities to human heart rate and overall cardiac function. The researchers were able to map out the composition, organisation and function of neurons within the heart using a combination of methods such as single-cell RNA sequencing, anatomical studies and electrophysiological techniques.

New therapeutic targets

“We will now continue to investigate how the heart’s brain interacts with the actual brain to regulate heart functions under different conditions such as exercise, stress, or disease,” says Konstantinos Ampatzis. “We aim to identify new therapeutic targets by examining how disruptions in the heart’s neuronal network contribute to different heart disorders.”

Source: Karolinska Institutet

Categories : ExerciseTags : Leave a comment

Home and Neighbourhood Environments Impact Sedentary Behaviour in Teens Globally

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Photo by Steinar Engeland on Unsplash

The World Health Organization recommends no more than two to three hours per day of sedentary time for youth. However, adolescents worldwide are spending an average of 8 to 10 hours per day engaging in sedentary activities such as watching television, using electronic devices, playing video games and riding in motorised vehicles, according to a 15-country study published in the International Journal of Behavioral Nutrition and Physical Activity.

The most notable finding of the study, led by principal investigator James F. Sallis, PhD, distinguished professor at University of California San Diego, and colleagues from 14 countries, found that simply having a personal social media account was linked with higher total sedentary time in both males and females. Social media was also related to more self-reported screen time.

“Although there is great concern about negative effects of social media on youth mental health, this study documents a pathway for social media to harm physical health as well,” said Sallis, who is also a professorial fellow at the Australian Catholic University.

“These findings are concerning, as excessive sedentary behavior has been linked to a range of health problems, including obesity, diabetes and mental health issues.”

Researchers analysed accelerometer data from 3,982 adolescents aged 11 to 19 and survey measures of sedentary behaviour from 6,02 participants in the International Physical Activity and the Environment Network (IPEN) Adolescent Study, which covered 15 geographically and culturally diverse countries across six continents.

The number of electronic devices within a home, how many adolescents had their own social media accounts and neighbourhood walkability were significantly different across countries.

For example, adolescents from India had an average of 1.2 electronic devices in the bedroom and 0.5 personal electronic devices, while the average number of such devices in Denmark was 4.2 and 2.3, respectively. In India and Bangladesh, fewer than 30% of adolescents reported having their own social media account, compared to higher socio-economic status countries where it was over 90%.

Parents reporting on walkability identified Australia as having high access to parks, while Nigerian parents reported no access, and parents in Bangladesh and India reported poor access. Traffic was a concern among parents in Brazil, Malaysia, Bangladesh, India, and Israel, and concerns about crime were high in the first three countries.

Adolescents who reported less recreational screen time lived in walkable neighbourhoods and had better perceptions of safety from traffic and crime than others. Girls who lived in neighbourhoods designed to support physical activity were less likely to be sedentary.

Despite differences in culture, built environments and extent of sedentary time, patterns of association were generally similar across countries, said the study’s lead author Ranjit Mohan Anjana, MD, PhD, of Dr Mohan’s Diabetes Specialties Centre and Madras Diabetes Research Foundation in India.

“Together, parents, policymakers and technology companies can work together to reduce access to screens, limit social media engagement and promote more physical activity, thus helping adolescents develop healthier habits and reduce their risk of chronic diseases,” said Anjana.

The study’s findings have significant implications for public health policy and highlight the need for further research into the causes and consequences of sedentary behaviour among teenagers.

Source: University of California – San Diego

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How Breast Cancer Cells Survive in Bone Marrow after Remission

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Photo by National Cancer Institute on Unsplash

A new study has shed light on a previously poorly understood aspect of breast cancer recurrence: how cancer cells survive in bone marrow despite targeted therapies. The paper appears in the Journal of Clinical Investigation. 

Oestrogen receptor positive (OR+) breast cancer is the most common form of the disease, and cancer cells of this kind can live for years in bone marrow after remission. The persistence of these cells in marrow leads to the disease recurring about 40% of patients. This return can take the form of especially aggressive bone cancer with symptoms such as bone fractures and hypercalcaemia. 

The cells can also spread to other organs, causing recurrent disease that is currently incurable. 

To better understand how these cancer cells survive, and why they cause such aggressive returning disease, researchers investigated what happens to these dispersed cells in bone marrow. 

Their key finding was the mechanism by which a normal cell type, mesenchymal stem cells, in the bone marrow supports the cancer cells.

“We discovered that the breast cancer cells require direct contact with mesenchymal stem cells,” said Gary Luker, MD, senior author on the paper.  

“The cancer cells physically borrow molecules – proteins, messenger RNA – directly from the mesenchymal stem cells. Essentially the mesenchymal stem cells act as very generous neighbours in donating things that make the cancer cells more aggressive and drug resistant.”

In laboratory experiments, contact between cancer cells and mesenchymal stem cells induced changes in hundreds of proteins. Further analysis of which proteins allowed for survival of breast cancer cells led researchers to focus on GIV, also known as Girdin. The paper notes that GIV drives “invasiveness, chemoresistance, and acquisition of metastatic potential in multiple cancers.”

GIV makes these cancer cells specifically resistant to oestrogen-targeted therapies, such as the drug Tamoxifen. The researchers hope this understanding of the mechanism of cancer cell survival will one day lead to treatments that prevent OR+ breast cancers from returning.

Sleeper cells can awaken

“Sleeper cells can be reawakened and cause oestrogen receptor positive breast cancers to relapse years –in some cases as long as a decade – after patients were believed to be in remission,” said study author Pradipta Ghosh, M.D., a professor in the Departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine.

“Since these cancer cells ‘borrow’ essential proteins from stem cells in the bone marrow through cellular tunnels – much like smuggling – approaches for targeting the tunnels or proteins they smuggle could help prevent the relapse and metastasis of oestrogen receptor positive breast cancer.”

Source: University of Michigan