Tag: 17/9/25

Categories : CancerTags :

New Cancer Drug Boosts Effectiveness of Chemotherapy – Even in Resistant Tumours

On By ModernMedia

A groundbreaking cancer drug could enhance how patients respond to chemotherapy even in treatment-resistant tumours.

The drug works by disarming a key defence mechanism that tumours use to protect themselves from treatment. In preclinical models, it has already shown promise in making chemotherapy-resistant cancers more responsive to therapy.

Chemotherapy is one of the most widely used cancer treatments, but it doesn’t always work as effectively as hoped. One major reason is that macrophages act as a barrier around tumours. These immune cells surround the blood vessels inside tumours and act like gatekeepers, blocking helpful immune cells from entering and doing their job in supporting the responses to chemotherapy.

The King’s College London scientists, who have launched a spinout company Aethox Therapeutics, found that these macrophages make a protein called heme oxygenase-1 (HO-1), which helps shield the tumour from the immune system and block the effects of chemotherapy. The new drug, KCL-HO-1i, targets this protein.

Professor James Arnold, Head of Tumour Immunology Group, King’s College London, said: “We discovered that these macrophages in cancer play a key role in blocking chemotherapy. By targeting the enzyme they produce using KCL-HO-1i, we were able to help beneficial immune cells and chemotherapy drugs become significantly more effective. In laboratory models, even chemotherapy-resistant tumours became responsive to treatment, which is a really exciting step forward.”

Unlike many cancer treatments that require hospital visits, KCL-HO1i is designed to be taken at home as a tablet between chemotherapy sessions. This makes it easier for patients to incorporate into their treatment plans without adding extra hospital burdens.

In early tests using mouse models of breast cancer, supported by funding by Cancer Research UK and Medical Research Council (MRC), the drug made tumours more responsive to a range of commonly used chemotherapies. These promising results suggest it could be used across a wide variety of cancer types and chemotherapy treatments.

The researchers hope that with funding, clinical trials on breast and other cancers could begin within two years.

Professor James Spicer, Professor of Experimental Cancer Medicine, King’s College London, said: “Chemotherapy remains a key part of treatment for many patients with cancer, but too often it is not as effective or long-lasting as we might like. This research has identified a key reason for these limitations, and discovered a drug that we are keen to test in the clinic alongside established chemotherapy drugs”.

This breakthrough is the result of a multidisciplinary collaboration between researchers including Professors James Arnold, James Spicer, and Miraz Rahman and their research teams at King’s College London.

If human trials are successful, KCL-HO-1i could become a valuable companion drug to existing cancer therapies – helping more patients to benefit from the treatments that are already available and reduce the need for more aggressive cancer therapies in the future.

Professor Miraz Rahman, Professor of Medicinal Chemistry, King’s College London
Categories : EndocrinologyTags :

Sleep and Growth Hormones Tightly Regulate One Another

On By ModernMedia
Photo by Zhenzhong Liu on Unsplash

As every bodybuilder knows, a deep, restful sleep boosts levels of growth hormone to build strong muscle and bone and burn fat. And as every teenager should know, they won’t reach their full height potential without adequate growth hormone from a full night’s sleep.

But why lack of sleep – in particular the early, deep phase called non-REM sleep — lowers levels of growth hormone has been a mystery.

In a study published in the current issue of the journal Cell, researchers from University of California, Berkeley, dissect the brain circuits in mice that control growth hormone release during sleep and report a novel feedback mechanism in the brain that keeps growth hormone levels finely balanced.

The findings provide a map for understanding how sleep and hormone regulation interact. The new feedback mechanism could open avenues for treating people with sleep disorders tied to metabolic conditions like diabetes, as well as degenerative diseases like Parkinson’s and Alzheimer’s.

“People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep,” said study first author Xinlu Ding, a postdoctoral fellow in UC Berkeley’s Department of Neuroscience and the Helen Wills Neuroscience Institute. “We’re actually directly recording neural activity in mice to see what’s going on. We are providing a basic circuit to work on in the future to develop different treatments.”

Because growth hormone regulates glucose and fat metabolism, insufficient sleep can also worsen risks for obesity, diabetes and cardiovascular disease.

The sleep-wake cycle

The neurons that orchestrate growth hormone release during the sleep-wake cycle – growth hormone releasing hormone (GHRH) neurons and two types of somatostatin neurons – are buried deep in the hypothalamus, an ancient brain hub conserved in all mammals. Once released, growth hormone increases the activity of neurons in the locus coeruleus, an area in the brainstem involved in arousal, attention, cognition and novelty seeking. Dysregulation of locus coeruleus neurons is implicated in numerous psychiatric and neurological disorders.

“Understanding the neural circuit for growth hormone release could eventually point toward new hormonal therapies to improve sleep quality or restore normal growth hormone balance,” said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author. “There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel handle to try to dial back the excitability of the locus coeruleus, which hasn’t been talked about before.”

The researchers, working in the lab of Yang Dan, a professor of neuroscience and of molecular and cell biology, explored the neuroendocrine circuit by inserting electrodes in the brains of mice and measuring changes in activity after stimulating neurons in the hypothalamus with light. Mice sleep for short periods – several minutes at a time – throughout the day and night, providing many opportunities to study growth hormone changes during sleep-wake cycles.

Using state-of-the-art circuit tracing, the team found that the two small-peptide hormones that control the release of growth hormone in the brain – GHRH, which promotes release, and somatostatin, which inhibits release – operate differently during REM and non-REM sleep. Somatostatin and GHRH surge during REM sleep to boost growth hormone, but somatostatin decreases and GHRH increases only moderately during non-REM sleep to boost growth hormone.

Released growth hormone regulates locus coeruleus activity, as a feedback mechanism to help create a homeostatic yin-yang effect. During sleep, growth hormone slowly accumulates to stimulate the locus coeruleus and promote wakefulness, the new study found. But when the locus coeruleus becomes overexcited, it paradoxically promotes sleepiness, as Silverman showed in a study published earlier this year.

“This suggests that sleep and growth hormone form a tightly balanced system: Too little sleep reduces growth hormone release, and too much growth hormone can in turn push the brain toward wakefulness,” Silverman said. “Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health.”

Because growth hormone acts in part through the locus coeruleus, which governs overall brain arousal during wakefulness, a proper balance could have a broader impact on attention and thinking.

“Growth hormone not only helps you build your muscle and bones and reduce your fat tissue, but may also have cognitive benefits, promoting your overall arousal level when you wake up,” Ding said.

Source: University of California – Berkeley

Categories : Expert Opinion Medical IndustryTags :

The Future of Pharmacies in South Africa Lies in Sustainable Expansion

On By ModernMedia
Photo by National Cancer Institute on Unsplash

By Christina Mooki, Head of Acquisition Operations at Merchant Capital

Pharmacies, especially ones in rural areas, are often the cornerstone of their communities. Beyond filling prescriptions, they provide medication, medical equipment, and counselling, sometimes serving as multi-service clinics in small towns and outlying areas. When people cannot wait weeks for a doctor’s appointment or need trusted advice, the local pharmacy is their first stop.

In many outlying areas, it is not just the most practical option, but often the only one. With the country’s high and rising burden of chronic disease, this role will only grow in importance.

The sector is indeed expanding. In just two years, 2020 and 2021, about 648 new community pharmacies opened across South Africa. By 2021, the total number stood at roughly 3580 outlets, and nearly 70% of these were independent rather than corporate-owned. That is over 2000 small businesses carrying community healthcare.

Christina Mooki, Head of Acquisition Operations at Merchant Capital

But every pharmacy is also a business. Behind the scenes, owners are juggling supplier deliveries, unpredictable supply chain issues, negotiating credit terms, paying staff, and trying to keep overheads under control. Balancing that with the responsibility of keeping communities healthy makes pharmacy ownership uniquely challenging and uniquely important.

Why more pharmacies are needed

A growing number of South Africans are living with chronic illness such as diabetes, hypertension, and HIV. These patients cannot miss their repeat medications and local pharmacy access becomes essential. Independent outlets do more than only dispense medicine, they also cut travel time, keep treatment within reach, and help build local economies.

Around the world, the role of a pharmacy is expanding. They are no longer limited to handing out prescriptions. According to Deloitte, many pharmacies are transforming into community health hubs by adding point-of-care testing, preventative health screening, and digital services to meet the changing expectations of modern consumers. Locally, they are also incorporating retail services to diversify their offerings further.

Running a pharmacy like a retailer

Passion for helping people will take you far as a pharmacist, but on its own, it will not keep the doors open. Independent pharmacies need to be run with the same discipline as any other retailer. Cash flow must be watched so staff are paid and suppliers are not left waiting. Shelves must carry the medicines that matter most without tying up money in products that sit for months. Costs like rent and electricity creep up quickly, and if unchecked, margins vanish.

Strong supplier relationships also make a difference. Paying on time, negotiating fairly, and keeping that trust intact can protect a business when times are tough. And like any other retailer, pharmacy owners have to be careful about how much debt they take on. Too much, too soon, can put even a busy store under pressure.

When these basics are in place, a pharmacy is not just a trusted point of care. It is also a resilient business that can think about growing, instead of simply surviving.

Where funding helps

Growth always asks for money before it offers returns. Anyone who has opened a second branch, hired staff, or added delivery knows this reality. The bills arrive first, and only later does the revenue follow. For a small independent owner working on thin margins, that can feel like a brick wall.

This is also the point where funding can be an enabler rather than a burden. At Merchant Capital, we treat pharmacies like retail businesses because that is what they are. They need capital that moves quickly, without red tape, and repayment models that flex with real turnover rather than with a rigid schedule. That flexibility gives owners breathing space, the confidence to back their instinct, invest in a new outlet, upgrade systems, or respond to their community.

Looking ahead

Independent pharmacies have already shown how vital they are to South Africa’s healthcare system. The next step is ensuring more of them open in the areas where they are most needed. With sound business management and access to the right kind of funding, these enterprises can grow their footprint, create jobs, and continue to provide reliable access to healthcare.

Categories : Respiratory DiseasesTags :

Researchers Identify Promising New Compound to Treat Tuberculosis

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As part of the ongoing fight against tuberculosis, scientists within Texas A&M AgriLife Research and Calibr-Skaggs have developed a promising new compound targeting a key bacterial enzyme on M. tuberculosis. The compound, using a novel mechanism, proved effective against even drug-resistant strains of tuberculosis in early studies. (Inna Krieger/Texas A&M AgriLife)

Scientists have developed a new compound that could offer a breakthrough in the global fight against tuberculosis, history’s deadliest infectious disease.

A study recently published in Nature describes the treatment potential of the novel compound known as CMX410. The drug uniquely targets a crucial enzyme in Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. Importantly, this compound even proved effective against drug-resistant infections, which are common globally and pose a significant challenge for controlling the disease’s spread and progression.

The study was led by James Sacchettini, PhD, the Rodger J. Wolfe-Welch Foundation Chair in Science, Texas A&M AgriLife Research scientist and professor in the Texas A&M College of Agriculture and Life Sciences Department of Biochemistry and Biophysics and College of Arts and Sciences Department of Chemistry. He was joined by Case McNamara, PhD, senior director of infectious disease at Calibr-Skaggs Institute for Innovative Medicines, the nonprofit drug development division of Scripps Research dedicated to accelerating next-generation medicines.

The discovery was made possible through collaborations formed by the TB Drug Accelerator program, an initiative funded by The Gates Foundation to support research focused on developing the most promising tuberculosis treatments.

“A lot of people think of tuberculosis as a disease of the past,” Sacchettini said. “But in reality, it remains a major public health issue requiring significant attention, collaboration and innovation to overcome.”

A smarter way to fight back

The new compound identified by AgriLife Research and Calibr-Skaggs works by blocking a crucial enzyme, polyketide synthase 13 or Pks13, that M. tuberculosis needs to build its protective cell wall. Without the functionality of this protein, the bacteria can’t survive to cause infection.

For over a decade, scientists have recognised this protein as a high-value target in the fight against tuberculosis. Yet, despite its potential, drug development efforts have repeatedly fallen short – largely because compounds must clear a high bar for both safety and therapeutic performance.

The unique mechanism of CMX410 makes it highly specific for its target, which translates to a favourable safety profile. By incorporating a reactive chemical group that forms an irreversible bond with a critical site on Pks13, the researchers enhanced the compound’s selectivity, minimising potentially negative off-target effects. This modification also reduces the likelihood of resistance emerging.

The addition of this key chemical group was accomplished with click chemistry, a method that snaps molecules together like puzzle pieces. Click chemistry was developed by co-author Barry Sharpless, Ph.D., W.M. Keck Professor of Chemistry at Scripps Research and two-time Nobel Laureate, and it has led to the development of extensive libraries of chemical compounds.

“This technique represents a new tool for drug design,” said McNamara. “We expect to see its uses expand in the coming years to help address public health concerns with a critical need, including tuberculosis.”

Early results prove safe and effective

The team began by investigating a library of compounds shared by the Sharpless lab to identify molecules that could inhibit bacterial growth of M. tuberculosis.

After intensive optimization to improve compound potency and other pharmacological properties led by Calibr-Skaggs tuberculosis team members and co-first authors Baiyuan Yang, Ph.D., associate director of medicinal chemistry, and Paridhi Sukheja, Ph.D., investigator of infectious diseases, CMX410 was identified as a strong contender.

Yang, who led the chemistry optimisation, said the team explored more than 300 analogues to identify a compound with the right balance of potency, selectivity and safety. The team ultimately tested CMX410 against 66 strains of M. tuberculosis and found that it worked on both laboratory and multidrug-resistant strains collected from real patients.

“Identifying this novel target was an exciting moment,” said Sukheja, who led many early studies showing CMX410 could target a previously unexplored gene. “It opened up a completely new path forward, especially against strains that have learned to evade existing treatments.”

In other early experiments, the researchers determined that CMX410 could be safely combined with other tuberculosis antibiotics. This was an especially important factor for this disease, as treatment regimens require multiple drugs to be taken together for months at a time.

Researchers found no adverse effects in their initial tests in animal models even at the maximum dose level. And because CMX410 is highly specific to its target protein, they see it as unlikely to disrupt other beneficial bacteria or cause broader microbiome imbalances, a common side effect of conventional antibiotics.

Progress toward better treatments

The addition of a specialised chemical group that allows CMX410 to irreversibly bind to its target makes the compound extremely selective. These types of inhibitors remain an exciting and underexplored class of drugs, and further research will be needed to confirm their safety for humans.

Nonetheless, the precision, unique mechanism, good safety profile and other key features all make CMX410 a promising candidate for treating tuberculosis.

“These early results are very encouraging,” said Inna Krieger, Ph.D., senior research scientist in Sacchettini’s lab and co-first author of the study. “Cell wall-targeting antibiotics have long been a cornerstone of tuberculosis treatment. However, after decades of widespread use, their effectiveness is waning due to the rise of drug-resistant strains.

“We are working to discover new drugs that disrupt essential biological processes and identify optimal combinations with existing drugs to enable shorter, safer and more effective treatment regimens. Through these efforts, we hope to help move the world closer to a future free from tuberculosis.”

Source: Scripps Research

Categories : Antibiotics Diet and NutritionTags :

Study Finds Caffeine Can Weaken Effectiveness of Certain Antibiotics

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Photo by Mike Kenneally on Unsplash

Ingredients of our daily diet – including caffeine – can influence the resistance of bacteria to antibiotics. This has been shown in a new study by a team of researchers at the Universities of Tübingen and Würzburg led by Professor Ana Rita Brochado. They discovered bacteria such as Escherichia coli (E. coli) orchestrate complex regulatory cascades to react to chemical stimuli from their direct environment which can influence the effectiveness of antimicrobial drugs such as ciprofloxacin.

In a systematic screening, Brochado’s team investigated how 94 different substances – including antibiotics, prescription drugs, and food ingredients – influence the expression of key gene regulators and transport proteins of the bacterium E. coli, a potential pathogen. Transport proteins function as pores and pumps in the bacterial envelope and control which substances enter or leave the cell. A finely tuned balance of these mechanisms is crucial for the survival of bacteria.

Researchers describe phenomenon as an ‘antagonistic interaction’

“Our data show that several substances can subtly but systematically influence gene regulation in bacteria,” says PhD student Christoph Binsfeld, first author of the study. The findings suggest even everyday substances without a direct antimicrobial effect – eg, caffeinated drinks – can impact certain gene regulators that control transport proteins, thereby changing what enters and leaves the bacterium. “Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli – which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” explains Ana Rita Brochado. This results in caffeine weakening the effect of this antibiotic. The researchers describe this phenomenon as an ‘antagonistic interaction.’

“Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli – which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” says Prof Brochado.

This weakening effect of certain antibiotics was not detectable in Salmonella enterica, a pathogen closely related to E. coli. This shows that even in similar bacterial species, the same environmental stimuli can lead to different reactions – possibly due to differences in transport pathways or their contribution to antibiotic uptake.

The study, which has been published in the scientific journal PLOS Biology, makes an important contribution to the understanding of what is called ‘low-level’ antibiotic resistance, which is not due to classic resistance genes, but to regulation and environmental adaptation. This could have implications for future therapeutic approaches, including what is taken during treatment and in what amount, and whether another drug or food ingredient – should be given greater consideration.

Source: University of Tübingen