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
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.
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.
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 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.”
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.
Since President Cyril Ramaphosa signed the NHI Act into law last year in May, eight different groups have challenged it in court. One common argument is that it is irrational and unreasonable to restructure the health system when there’s no money to do so. In this feature, Spotlight dissects how the argument is being applied, and whether it has any chance of success.
Earlier this month, the Western Cape Government filed papers with the Constitutional Court challenging the validity of the National Health Insurance (NHI) Act. In doing so, it became the eighth group to litigate against the Act, which aims to provide the same state-funded medical cover for all South Africans.
Not only are there now numerous litigants, each with their own distinct set of arguments, but some have also launched multiple applications, challenging different steps that led to it becoming law.
In this context, figuring out on which legal questions the future of the NHI Act will ultimately turn is difficult. Thus, Spotlight combed through some of the founding affidavits and spoke with legal experts to get a sense of the arguments litigants are betting on. A first key argument relates to the affordability of the scheme – in part two of this series we will turn to whether the NHI leads to an unreasonable regression in health services for certain groups.
Rationality and reasonability
Section 1(c) of the Constitution of the country holds that South Africa is a state governed by the rule of law. One of the implications of this is that governments can’t simply introduce laws arbitrarily without any justification. Instead, when an Act is passed, there has to be some aim behind that legislation, and some logical reason as to why passing it would advance that aim.
In other words, laws have to be rational.
Not only this, but Section 27 of the Constitution states that when it comes to the advancement of certain social rights like healthcare, government must act “reasonably”. This is a more demanding requirement than “rationality”. It doesn’t just require that an Act be logically related to its purpose but that it is practically feasible, and that it meets a range of other criteria (for instance, costs and benefits have to be fairly weighed).
A central argument of several litigants is that the NHI simply doesn’t meet basic standards of rationality or reasonability. One of the reasons for this, they argue, is that the government is unable to finance the NHI, and thus the Act has no hope of achieving its goals.
There are at least two ways in which this argument is being advanced. The first is as part of a series of applications seeking to invalidate the NHI Act itself. The second is as part of a procedural challenge to President Cyril Ramaphosa’s decision to sign the NHI Act into law. Here, the focus is on the rationality of the President’s decision, rather than the Act.
Challenging the act itself
The first party to take legal action against the NHI was the conservative trade union, Solidarity, which launched its application in the North Gauteng High Court in Pretoria on 24 May 2024.
In its founding affidavit, Solidarity argued that for the NHI to achieve its stated aim of universal access to quality healthcare services, the “requisite level of funding” must be available to establish the NHI Fund and its various mechanisms. But according to Solidarity’s application, it has already been shown that the government is incapable of raising enough tax revenue to support the scheme.
For instance, Solidarity references the position of the Davis Tax Committee, which was a group of experts chaired by Judge Dennis Davis that used to advise the government on how it could raise money to advance various policy goals. In 2017, the committee released a 48-page report on the NHI, which found that the state couldn’t cover the full cost of the NHI unless there was “sustained economic growth”.
Solidarity stated that this, in combination with its own research, showed that the NHI simply can’t be rolled out comprehensively. Thus, there was a “complete absence of a rational relation between the means selected and the objective sought to be achieved”.
Similarly, in February, a separate challenge was brought by the Hospital Association of South Africa (HASA), which argued that the NHI should be set aside because it is “fundamentally unreasonable and therefore unconstitutional”.
HASA’s submission argued that the burden of proof lay with the government to show that the NHI was financially feasible before passing the Act. This is particularly important given that the scheme involves a radical restructuring of healthcare with potentially detrimental knock-on effects for the private sector. The government thus had a duty to show that the scheme could lead to material benefits that justified these harms.
However, HASA argues that “no recent comprehensive and accurate financial feasibility and affordability assessment was conducted” by the government before pushing through the NHI, rendering “the passing of the legislation unreasonable and irrational”.
For its part, the National Department of Health has argued in court papers that trying to work out the full cost of the NHI would be a futile exercise. For instance, the health department’s NHI lead, Nicholas Crisp, filed an affidavit in response to Solidarity which stated that “attempts to conduct a once-off accounting exercise” were “not useful”.
He said: “The outcome of such an exercise is inevitably inaccurate, misleading and does not support informed decision making for reform.” Crisp argued that this was already evident from the “extremely wide range of figures that various parties have claimed to reflect the cost of the NHI in the public domain”.
Instead, Crisp stated that the World Health Organization (WHO) had advised the department to conduct an “ongoing costing approach for specific steps of the NHI implementation process”, which is something they were already doing, he said.
Nonetheless, many of the litigants have pushed back against this, arguing that this approach still leaves us without any evidence that the NHI can be funded in the medium to long term. In its affidavit, HASA argues: “In the context of constrained public finances and very challenging economic conditions… it is wholly irrational to commence the wholesale restructuring of the healthcare sector without long-term costing, and only with short-term piece-meal analysis”.
Challenging the President’s decision
While the above applications have sought to review and set aside the NHI Act itself, a separate set of challenges has instead focused on the decision of Ramaphosa to sign the Bill into law.
Section 79(1) of the Constitution states that if the President “has reservations about the constitutionality of the Bill”, then he should refer it back to Parliament for reconsideration.
If it can be proved that Ramaphosa had good evidence that the NHI may have been unconstitutional, but signed it anyway, then his decision can potentially be overturned by a court. In this case, the NHI wouldn’t be completely invalidated and set aside, but the President’s decision to sign it into law would be. Therefore, the NHI would go back to being a Bill, and would likely need to be reworked by Parliament.
President Cyril Ramaphosa holds a copy of the NHI Act after publicly signing into law in May 2024. (Photo: GCIS)
The Board of Health Funders (BHF), which represents medical insurance companies, is one of the litigants taking this approach. In addition, the South African Private Practitioners Forum (SAPPF) has a two-part application challenging both the Act itself and Ramaphosa’s decision to sign it.
Once again, the affordability argument has been central in these cases. In particular, the BHF and SAPPF have both highlighted a number of documents that were sent to Ramaphosa before he signed the NHI Act, which they argue should have caused the President to reconsider whether the Act was affordable.
For instance, the parties note that in 2018, the Office of the Presidency received a letter from the acting director-general of Treasury which expressed several concerns about what was then the NHI Bill. One of them was that the “financial implications are not costed”. As a result of issues such as this, the acting director-general felt “unable to support the bill in the current form submitted to cabinet”.
The BHF affidavit points out that the version of the Bill that Treasury had commented on was “not materially altered” later on. It further states that the letter from Treasury “was before the president when he assented to the NHI Bill and it is unclear at this stage the basis on which the president disagreed with the views of Treasury”.
In order to properly evaluate the rationality of Ramaphosa’s decision, the applications by BHF and SAPPF have been seeking to have the full record of his decision made public. The record refers to any information he would have had before him when signing the bill into law, as well as any minutes of correspondences he had which related to the Act.
The BHF and SAPPF have already made some progress with their case. In May, the North Gauteng High Court in Pretoria ruled that it was able to review Ramaphosa’s decision to sign the NHI Bill into law, and gave the President 10 days to provide the full record of his decision to do so.
Neil Kirby, who heads the healthcare and life science practice area at Werksman’s Attorneys, which represents BHF, told Spotlight that after the ruling, “both the [health] minister and the president made application for leave to appeal that judgment which is a process that’s supposed to happen before the original judge. They also then proposed that they appeal directly to the constitutional court.”
He adds: “At this point in time the high court has taken a step back on the basis that the high court wants to wait for the constitutional court via the chief justice to see what to do about those direct applications.”
Thus, until the Chief Justice provides direction, Kirby says “everything is in limbo”.
In the meantime, the BHF has also launched a separate application at the Constitutional Court, which challenges the public participation process prior to Ramaphosa signing the NHI Act. The focus here is on the rationality and reasonability of Parliament’s consideration of the NHI Bill, which they argue failed to consider input from various parties. As with the other application, the affordability argument plays a role.
Kirby explains: “If you’re sitting in the National Assembly and you’re being asked to vote on a Bill that proposes a significant financial burden on the state in due course and you don’t have the figures in front of you to understand what that burden actually is, then you’re not in a position to say that such a thing is a good idea… It’s grounds for review based on the reasonableness and the rationality of [that] decision”.
How powerful is the affordability argument?
According to Kirby, the argument about affordability is by no means the only strong line of attack that the BHF possesses against the NHI, but it is easily one of the most powerful.
According to Dr Larisse Prinsen, a medico-legal expert at the University of the Free State, who is not involved in the litigation, the affordability argument is more likely to be successful as a line of attack against the President’s assent to the legislation (as with the BHF’s case). Though it would be unlikely to suffice on its own, she says.
Prinsen explains that if the “record shows that the President ignored massive red flags, such as the warnings by the [Davis Tax Committee] and Treasury regarding concerns about the sustainability of the NHI, unresolved costing, provincial power concerns etc., this could support the claim of irrationality in the decision-making process”.
However, she says when it comes to the legal challenges to the Act itself, the argument about affordability is less likely to be successful.
“Courts often defer where a law creates a framework with a phased roll-out and which leaves fiscal choices to later money bills,” she says. “The government might use annual appropriations or future revenue decisions or phased progressive implementation to argue the NHI scheme is in fact capable of reasonable realisation over time. This means that outright invalidation on ‘infeasibility’ alone is a harder battle to fight.”
Similarly, another attorney who is also independent of the litigation, told Spotlight that rationality reviews are typically aimed at procedural steps in the formation of an Act. Thus, the challenge to the President’s decision to sign the law, would likely carry more weight, he said.
Note: In part two of this series, we will turn to whether the implementation of NHI, as set out in the NHI Act, will lead to an unreasonable regression in health services for certain groups.
As the effectiveness of antibiotics meant to fight the deadly superbug Clostridioides difficile wanes, a research team at the University of Houston is seeing positive results of a new antibiotic on the scene – ibezapolstat – which is proving successful in fighting these infectious bacteria in clinical trials.
C. diff is a leading cause of death from gastroenteritis, causing gastrointestinal illness ranging from diarrhoea and abdominal pain to toxic megacolon, sepsis and death.
Until now the frontline treatments for C. diff have been the antibiotics vancomycin, with a sustained clinical cure of 42% to 71%, and fidaxomicin at 67%.
And yet, a superbug would not be so deadly if it was not able to outlive the very medicines meant to destroy it.
“Both vanco and fidaxo are associated with emerging antimicrobial resistance. C. difficile infection recurrence is associated with increased mortality, decreased quality of life and higher healthcare costs. New antibiotics are urgently needed,” said Kevin Garey, Professor of Drug Discovery at the University of Houston College of Pharmacy and senior author on recent clinical trial results with ibezapolstat published in Lancet Microbe.
C. diff infections often return when the natural balance in the gut stays disrupted – good bacteria like Bacillota, Bacteroidota, and Actinomycetota are reduced, while harmful types like Pseudomonadota increase. These changes can weaken the gut’s defences, causing a loss of the kind of bacteria that helps break down bile acids. When that happens, harmful bacteria can easily take over.
“Ibezapolstat’s mechanism of action helps restore the healthy microbiota that causes C. diff recurrence” said study lead author Taryn A. Eubank, research assistant professor of Pharmacy Practice and Translational Research at UH.
Enter ibezapolstat
Ibezapolstat has a way of working that kills harmful C. difficile bacteria without harming the good bacteria in the gut that protect against C. diff infections.
“A randomized, double-blind, active-controlled study showed high rates of initial clinical cure in participants treated with ibezapolstat, with no recurrence,” reports Garey.
“Ibezapolstat was found to be safe, well tolerated, and was associated with the preservation of key health-promoting bacteria responsible for bile acid homoeostasis, a key component in preventing recurrent C. difficile infection.”
Eubank added, “This helps confirm the important anti-C diff recurrence properties of Ibezapolstat.”
Ibezapolstat is being developed by Acurx Pharmaceuticals progressing towards phase III clinical trials. The study was conducted at 15 centres, primarily outpatient clinics and hospitals in the United States. Participants were aged 18–90 years, with diarrhoea and a confirmed diagnosis of mild or moderate C. difficile infection.
“The findings of our study support further clinical development of ibezapolstat into phase III clinical trials and eventual use in our patients,” said Garey.
What compels someone to keep engaging in alcohol use, even if it damages their health, relationships and wellbeing? A new study from Scripps Research offers an important clue: a small midline brain region plays a key role in how animals learn to continue drinking to avoid the stress and misery of withdrawal.
In a new study, published in Biological Psychiatry: Global Open Science on August 5, 2025, the Scripps Research team zeroed in on a set of brain cells in the paraventricular nucleus of the thalamus (PVT) in rats. They found that this region becomes more active, driving strong relapse behaviour, when rats learn to associate environmental stimuli with the easing of withdrawal symptoms by alcohol. By illuminating this brain pathway, the research sheds light on one of the most stubborn features of addiction – drinking not for pleasure, but to escape pain – and could eventually lead to new treatments for substance use disorders (SUDs) as well as other maladaptive behaviours including anxiety.
“What makes addiction so hard to break is that people aren’t simply chasing a high,” says Friedbert Weiss, professor of neuroscience at Scripps Research and senior author of the study. “They’re also trying to get rid of powerful negative states, like the stress and anxiety of withdrawal. This work shows us which brain systems are responsible for locking in that kind of learning, and why it can make relapse so persistent.”
“This brain region just lit up in every rat that had gone through withdrawal-related learning,” says co-senior author Hermina Nedelescu of Scripps Research. “It shows us which circuits are recruited when the brain links alcohol with relief from stress – and that could be a game-changer in how we think about relapse.”
From behaviour to brain maps
An estimated 14.5 million people in the United States have alcohol use disorder, which encompasses a range of unhealthy drinking behaviours. Like other drug addictions, alcohol addiction is characterised by cycles of withdrawal, abstinence and relapse.
In 2022, Weiss and Nedelescu used rats to study the types of learning that happen in the brain throughout this cycle. When rats initially begin drinking, they learn to associate pleasure with alcohol and seek more. However, that conditioning becomes far stronger during multiple cycles of withdrawal and relapse. After learning that alcohol eased the unpleasant feelings of withdrawal – negative reinforcement, or a relief of ‘negative hedonic state’ – the animals sought out more alcohol and would remain persistent even when uncomfortable.
“When rats learn to associate environmental stimuli or contexts with the experience of relief, they end up with an incredibly powerful urge to seek alcohol in the presence of that stimuli –even if conditions are introduced that require great effort to engage in alcohol seeking,” says Weiss. “That is, these rats seek alcohol even if that behavior is punished.”
In the new work, the team wanted to pin down exactly what networks of cells in the brain were responsible for learning to associate environmental cues with the relief of this negative hedonic state.
The researchers used advanced imaging tools to scan entire rat brains, cell by cell, and pinpoint areas that became more active in response to alcohol-related cues. They compared four groups of rats: those that had gone through withdrawal and learned that alcohol relieves a negative hedonic state, and three different control groups that had not.
While several brain areas showed increased activity in the withdrawal-learned rats, one stood out: the PVT, which is known for its role in stress and anxiety.
“In retrospect, this makes a lot of sense,” says Nedelescu. “The unpleasant effects of alcohol withdrawal are strongly associated with stress, and alcohol is providing relief from the agony of that stressful state.”
The researchers hypothesise that this negative hedonic state, and the activation of the PVT in the brain as a response, is critical for how the brain learns and perpetuates addiction.
A better understanding of addiction
The implications of the new study extend well beyond alcohol, the researchers say. Environmental stimuli conditioned to negative reinforcement – the drive to act in order to escape pain or stress – is a universal feature of the brain, and can drive human behaviour beyond substance use disorders such as anxiety disorders, fear-conditioning and traumatic avoidance learning.
“This work has potential applications not only for alcohol addiction, but also other disorders where people get trapped in harmful cycles,” says Nedelescu.
Future research will zoom in even further. Nedelescu and colleagues at Scripps Research want to expand the study to females and to study neurochemicals released in the PVT when subjects encounter environments associated with the experience of this relief from a negative hedonic state. If they can pinpoint molecules that are involved, it could open new avenues for drug development by targeting those molecules.
For now, the new study underscores a key shift in how basic scientists think about addiction.
“As psychologists, we’ve long known that addiction isn’t just about chasing pleasure – it’s about escaping those negative hedonic states,” says Weiss. “This study shows us where in the brain that learning takes root, which is a step forward.”
A new study tracked the acute muscle-building response in adults engaged in a weight-training exercise who were fed either high-fat or lean ground pork burgers with the same amount of protein in each. The findings surprised the scientists, adding to the evidence that muscle-protein synthesis in response to weight-training and a post-exercise meal is as complex as the high-protein foods people consume.
“What we’re finding is that not all high-quality animal protein foods are created equal,” said Nicholas Burd, a professor of health and kinesiology at the University of Illinois Urbana-Champaign, who led the research with graduate student Žan Zupančič.
A previous study from Burd’s lab found that consuming whole eggs after weight training was better for muscle-protein synthesis than eating only egg whites with equal amounts of protein. Another study from his lab revealed that eating salmon showed a more favourable rate of muscle-building after weight training than a processed mixture containing the same nutrients in the same proportions as the salmon.
These studies suggest that whole foods are better at stimulating post-workout protein synthesis than their processed counterparts, and that the fat content of whole foods may, in some circumstances, improve the rate of muscle-building, Burd said.
In the new study, the researchers used state-of-the-art methods to trace and calculate muscle-protein synthesis in 16 young, physically active adults. The team turned to the U. of I.’s Meat Science Laboratory for formulation of the pork patties.
“That took us a year because it was so hard to get those fat ratios correct,” Burd said. All the meat used in the study came from a single pig, and the researchers sent the patties off to another laboratory for analysis. Once the lean-to-fat ratios and other macros were confirmed, the pork burgers were frozen until needed in the feeding part of the study.
Before the weight-training and feeding intervention, all participants received an infusion of isotope-labeled amino acids. This allowed the researchers to track how quickly the labeled amino acids were incorporated into muscle. The team also took blood samples throughout the study to measure amino acid levels in participants’ blood.
Before and after the first two hours of the infusion, researchers took muscle biopsies of each participant to get a baseline measure of muscle-protein synthesis.
“And then we took them to the gym,” Burd said. “And they were wheeling that infusion pump and everything else with them.”
At the gym, the study subjects engaged in an acute bout of leg presses and leg extensions and then returned to the lab for a meal of either a high-fat pork burger, a lean pork burger or a carbohydrate drink. Five hours after the meal, another muscle biopsy was taken to measure protein synthesis in response to the weight-training and feeding intervention.
After a break of a few days, 14 of the 16 participants “crossed over, switching to a different feeding intervention to minimise the impact of individual differences in muscle-building responses,” Burd said.
The analysis revealed, as expected, that the amino acid content of the blood was significantly higher in those who ate pork than in those who consumed a carbohydrate drink. But the lean-pork group saw the greatest gains in amino acid levels in the blood. This was true for total and essential amino acids, the team found.
“When you see an increased concentration of amino acids in the blood after you eat, you get a pretty good idea that that is coming from the food that you just ate,” Burd said.
Those who consumed the lean pork burger after a bout of weight training also had a greater rate of muscle-protein synthesis than those who ate the high-fat pork burger. This was a surprise to Burd, as “the previous studies using fattier foods, such as whole eggs or salmon, generally showed enhanced post-exercise muscle-protein synthesis compared with lower fat food such as egg whites or nutritional supplements,” he said.
Although weight training boosted muscle-protein synthesis in the groups eating pork, the protein in the high-fat burger seemed to have no added benefit in the hours after participants consumed it, while the protein in the lean pork gave muscle-protein synthesis a boost.
“For some reason, the high-fat pork truly blunted the response,” Burd said. “In fact, the people who ate the high-fat pork only had slightly better muscle-building potential than those who drank a carbohydrate sports beverage after exercise.”
Interpreting the results of this study for people who want to optimise muscle gains from weight-training is tricky, Burd said. It could be that processing the ground pork patties, which involved grinding the meat and adding the fattier meat to the lean, affected the kinetics of digestion.
“There was a little larger rise in the amino acids available from eating lean pork, so it could have been a bigger trigger for muscle-protein synthesis,” Burd said. “But that seems to be specific to the ground pork. If you’re eating other foods, like eggs or salmon, the whole foods appear to be better despite not eliciting a large rise in blood amino acids.”
Burd stresses that exercise is the strongest stimulus for muscle-protein synthesis.
“Most of the muscle response is to weight-training, and we use nutrition to try to squeeze out the remaining potential,” he said. “When it comes to eating after weight-training, what we’re finding is that some foods, particularly whole, unprocessed foods seem to be a better stimulus.”
Infants with high levels of antibiotic-resistant bacteria face a greater risk to their health if they need to be treated with antibiotics when they contract infectious diseases during their first year of life. Now, researchers at the Technical University of Denmark have discovered a way to combat antibiotic-resistant bacteria by nourishing a special subgroup of bifidobacteria found in the gut.
The research project, recently published in the renowned journal Nature Communications, points to a new, natural strategy for combating antibiotic resistance: supporting the good bacteria in the gut from the very first months of life.
“We document that special lactic acids produced by bifidobacteria play a key role in keeping antibiotic-resistant bacteria at bay, which is important for reducing the risk of resistance genes being transferred to other bacteria in the gut. Resistance genes can jump from one type of bacteria to another, and the more bacteria with resistance that are present in the gut, the greater the chance that they will encounter other bacteria and transfer resistance genes to them,” says postdoc Ioanna Chatzigiannidou from DTU Bioengineering, who participated in the research project.
The study of gut bacteria is based on 547 stool samples from 56 children and their mothers, who were followed over a five-year period.
A matter of life and death for infants
Professor Susanne Brix Pedersen from DTU Bioengineering is the head of the research project and explains that the new knowledge about bifidobacteria can be better utilized in society when researchers have developed a rapid test for use in the first weeks of a child’s life, so that parents can check whether their child already has these bifidobacteria naturally or would benefit from receiving a supplement containing them.
“It will be very important if we can strengthen their ability to handle antibiotic-resistant bacteria from the first weeks of a child’s life. This is especially true in the first year of life where infants are exposed to many infectious diseases due to an immature immune system, and when it is a matter of life and death if they have many antibiotic-resistant bacteria, for instance the pneumonia bacteria Klebsiella pneumoniae, making it difficult to treat pneumonia with certain antibiotics,” says Susanne Brix Pedersen.
There is a lot of research into antibiotic resistance, and Susanne Brix Pedersen is also involved in another study, BEGIN, which is based in the paediatric department at Aarhus University Hospital, where researchers are investigating whether a dietary supplement containing beneficial bifidobacteria can strengthen the immune system of newborn babies. So far, the trial has involved 300 women and their newborn babies, who are given either a placebo or a dietary supplement containing the special bifidobacteria.
