Month: August 2024

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Celebrating Aurélien Breton: A Champion of Patient Access to Innovation in South Africa

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In a world where healthcare challenges are evolving at an unprecedented pace, innovative leadership has become the cornerstone of transformative progress. 

Visionaries such as Aurélien Breton exemplify this dynamic approach, blending passion with strategic insight to drive meaningful change. By placing patient wellbeing at the heart of their mission, these leaders are not merely navigating the complexities of the healthcare landscape, but redefining it. 

Their commitment to advancing patient access and optimising care underscores a powerful message: that true leadership in healthcare is about more than just responding to current needs, but anticipating future demands and crafting solutions that elevate the quality of life for patients around the globe.

For nearly five years, Aurélien has been a driving force within the Innovative Pharmaceutical Association of South Africa (IPASA), serving as a cornerstone of the Executive Committee and leading the Patient Access to Innovation (PAI) Working Group. 

His journey with IPASA reflects a deep commitment to improving patient access to life-saving medicines, tackling the significant challenges within South Africa’s healthcare system, and advocating for those most in need.

“For me, being a part of IPASA means engaging in a collective effort that extends beyond personal or corporate interests to enhance the broader healthcare landscape in South Africa,” says Aurélien.

A native of France and current Managing Director of Southern and Eastern Africa at Servier, Aurélien’s passion for healthcare brought him to South Africa in 2019 driven by a desire to contribute to something greater than himself and to make a meaningful difference in the lives of all South African patients. 

“I am a firm believer that a true leader is someone who wakes up every morning driven by a deep sense of purpose. For me, that purpose is ensuring access to innovative medicines for those who need them most. Our work in providing medicines transcends mere numbers; it profoundly impacts the lives of patients and their families, enhancing their quality of life and serving a greater purpose beyond business,” he adds.

While Aurélien’s role has evolved since joining IPASA, his mission has remained constant – to address barriers to patient access and help patients benefit from innovative medicines. Under his leadership, the PAI Working Group has engaged key stakeholders, including government bodies, medical schemes, and patient advocacy groups, to improve access to innovative treatments. 

Aurélien admits that despite engaging with all relevant stakeholders, progress has been sluggish. He attributes this to the healthcare environment at large, where excessive processes and regulations dilute responsibilities and hinder effective action. 

“Constructing a path to improvement is challenging due to unresponsiveness and barriers, including a lack of urgency from some stakeholders and uncertainty surrounding the National Health Insurance (NHI) scheme. This has slowed efforts to enhance patient access to life-saving medicines. We must focus on refining the existing system rather than waiting for a complete overhaul.”

Despite these challenges, including others such as infrastructure, access to innovative medicines and their associated high costs, Aurélien and the team have made significant strides. Most notably, the Group has been instrumental in fostering strong engagement between medical schemes, the Council for Medical Schemes, patient advocacy groups, and others; while several prominent medical schemes, such as Discovery Health and Medscheme have entered into agreements that could improve access to innovative medicines in the future. 

Aurélien is quick to credit the collective efforts and dedication of the PAI Working Group for the progress achieved during his tenure, acknowledging their willingness to invest time and energy in something greater than themselves. He recognises the significant long-term commitment required, noting the burdensome and relentless nature of the work, which can lead to discouragement or frustration. Despite facing hurdles, the PAI Working Group has met these with resilience and determination to drive progress and effect meaningful change.

While Aurélien has helped achieve significant strides in improving patient access across the South African healthcare landscape, he is eager to broaden his impact by extending his expertise to other countries where he will continue his work in improving patient access.  

“While I am sad to be moving from South Africa, I believe I have helped set the foundation for change in the country. Even though the registration of innovative medicines has improved, access to these potentially life-saving medicines and increasing the public visibility of patient voices remains a challenge. I implore everyone involved to continue working tirelessly to break down these barriers, ensuring that all patients can benefit from the innovations that have the power to transform their lives. The work is far from over, and we must maintain our commitment to improving healthcare access and outcomes for all,” concludes Aurélien. 

Reflecting on Aurélien’s contributions, Bada Pharasi, CEO at IPASA, adds: “Aurélien’s commitment to improving patient access and healthcare innovation reflects a deep-seated passion for making a tangible difference. As he embarks on this new chapter, we, as IPASA, thank him for his commitment and drive to contribute positively to the healthcare landscape in South Africa. His influence will undoubtedly continue to inspire and impact many in the industry.”

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Online ‘FoMO’ can Cause Employees to Burn Out

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Photo by Vitaly Gariev on Unsplash

Fear of missing out (FoMO) is a key risk factor for employee mental health and, along with information overload, may increase burnout, according to new research.

Researchers from the University of Nottingham’s Schools of Psychology and Medicine analysed survey data from 142 employees to investigate the ‘dark side’ of digital working and found that employees who are worried about missing out on information and are overloaded by it are more likely to suffer stress and burnout. The results have been published today in SAGE Open.

The digital workplace is now recognised as a key strategic asset in organisations that enables worker productivity and flexibility in context of hybrid working. However, the potential downsides in terms of worker well-being also need to be considered, especially given the proliferation of digital communication channels and tools since Covid.

Elizabeth Marsh, PhD student from the School of Psychology

This new study connects to previous work which revealed that employees who are more mindful in the digital workplace are better protected against stress, anxiety and overload.

In this research FoMO is defined as anxiety about missing out on both important information and updates, as well as opportunities for relationships and interactions. FoMO has long been a term used in relation to social media, and now this new research shows it is an effect that is being felt in the workplace.

The participants in the study were surveyed about their experiences of the dark side effects of the digital workplace which were identified as; stress, overload, anxiety and fear of missing out and how these affected their wellbeing.

The results showed that among the dark side effects, those relating to information – both feeling overloaded by it and fearing missing out on it – proved particularly detrimental for well-being both directly and by elevating overall stress related to digital working.

Elizabeth adds: “The glut of information flowing through channels such as email, intranets or collaboration tools can lead workers to worry about missing out on it as well as succumbing to overload as they strive to keep up. To help people cope with information overwhelm, serious and sustained attention should be given to both optimising information management and supporting information literacy.”

The research makes some practical suggestions for employers which include investing in practices to optimise the amount and flow of information to employees. The findings could also be used by HR departments to consider policy and training options that would support the end-users of the digital workplace to better access, manage and consume information in a way that is conducive to well-being as well as productivity.

Consideration of the digital workplace in work and job design is essential to not only employee productivity but also well-being in modern organisations. Where this is lacking, elevated stress and burnout as well as poorer mental health may result. Our findings indicate the information ecosystem as an important area for attention both inside organisations and among the research community.

Professor Alexa Spence, School of Psychology

Source: University of Nottingham

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New Brain–computer Interface Allows Man with ALS to ‘Speak’ Again

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A new brain-computer interface (BCI) developed at UC Davis Health translates brain signals into speech with up to 97% accuracy – the most accurate system of its kind. The researchers implanted sensors in the brain of a man with severely impaired speech due to amyotrophic lateral sclerosis (ALS). The man was able to communicate his intended speech within minutes of activating the system.

A study about this work was published in the New England Journal of Medicine.

ALS, also known as Lou Gehrig’s disease, affects the nerve cells that control movement throughout the body. The disease leads to a gradual loss of the ability to stand, walk and use one’s hands. It can also cause a person to lose control of the muscles used to speak, leading to a loss of understandable speech.

The new technology is being developed to restore communication for people who can’t speak due to paralysis or neurological conditions like ALS. It can interpret brain signals when the user tries to speak and turns them into text that is ‘spoken’ aloud by the computer.

“Our BCI technology helped a man with paralysis to communicate with friends, families and caregivers,” said UC Davis neurosurgeon David Brandman. “Our paper demonstrates the most accurate speech neuroprosthesis (device) ever reported.”

Brandman is the co-principal investigator and co-senior author of this study. He is an assistant professor in the UC Davis Department of Neurological Surgery and co-director of the UC Davis Neuroprosthetics Lab.

The new BCI breaks the communication barrier

When someone tries to speak, the new BCI device transforms their brain activity into text on a computer screen. The computer can then read the text out loud.

To develop the system, the team enrolled Casey Harrell, a 45-year-old man with ALS, in the BrainGate clinical trial. At the time of his enrolment, Harrell had weakness in his arms and legs (tetraparesis). His speech was very hard to understand (dysarthria) and required others to help interpret for him.

In July 2023, Brandman implanted the investigational BCI device. He placed four microelectrode arrays into the left precentral gyrus, a brain region responsible for coordinating speech. The arrays are designed to record the brain activity from 256 cortical electrodes.

“We’re really detecting their attempt to move their muscles and talk,” explained neuroscientist Sergey Stavisky. Stavisky is an assistant professor in the Department of Neurological Surgery. He is the co-director of the UC Davis Neuroprosthetics Lab and co-principal investigator of the study. “We are recording from the part of the brain that’s trying to send these commands to the muscles. And we are basically listening into that, and we’re translating those patterns of brain activity into a phoneme – like a syllable or the unit of speech – and then the words they’re trying to say.”

Casey Harrell with his personal assistant Emma Alaimo and UC Davis neuroscientist Sergey Stavisky

Faster training, better results

Despite recent advances in BCI technology, efforts to enable communication have been slow and prone to errors. This is because the machine-learning programs that interpreted brain signals required a large amount of time and data to perform.

“Previous speech BCI systems had frequent word errors. This made it difficult for the user to be understood consistently and was a barrier to communication,” Brandman explained. “Our objective was to develop a system that empowered someone to be understood whenever they wanted to speak.”

Harrell used the system in both prompted and spontaneous conversational settings. In both cases, speech decoding happened in real time, with continuous system updates to keep it working accurately.

The decoded words were shown on a screen. Amazingly, they were read aloud in a voice that sounded like Harrell’s before he had ALS. The voice was composed using software trained with existing audio samples of his pre-ALS voice.

At the first speech data training session, the system took 30 minutes to achieve 99.6% word accuracy with a 50-word vocabulary.

“The first time we tried the system, he cried with joy as the words he was trying to say correctly appeared on-screen. We all did,” Stavisky said.

In the second session, the size of the potential vocabulary increased to 125 000 words. With just an additional 1.4 hours of training data, the BCI achieved a 90.2% word accuracy with this greatly expanded vocabulary. After continued data collection, the BCI has maintained 97.5% accuracy.

“At this point, we can decode what Casey is trying to say correctly about 97% of the time, which is better than many commercially available smartphone applications that try to interpret a person’s voice,” Brandman said. “This technology is transformative because it provides hope for people who want to speak but can’t. I hope that technology like this speech BCI will help future patients speak with their family and friends.”

The study reports on 84 data collection sessions over 32 weeks. In total, Harrell used the speech BCI in self-paced conversations for over 248 hours to communicate in person and over video chat.

“Not being able to communicate is so frustrating and demoralising. It is like you are trapped,” Harrell said. “Something like this technology will help people back into life and society.”

“It has been immensely rewarding to see Casey regain his ability to speak with his family and friends through this technology,” said the study’s lead author, Nicholas Card. Card is a postdoctoral scholar in the UC Davis Department of Neurological Surgery.

“Casey and our other BrainGate participants are truly extraordinary. They deserve tremendous credit for joining these early clinical trials. They do this not because they’re hoping to gain any personal benefit, but to help us develop a system that will restore communication and mobility for other people with paralysis,” said co-author and BrainGate trial sponsor-investigator Leigh Hochberg. Hochberg is a neurologist and neuroscientist at Massachusetts General Hospital, Brown University and the VA Providence Healthcare System.

Brandman is the site-responsible principal investigator of the BrainGate2 clinical trial. The trial is enrolling participants. To learn more about the study, visit braingate.org or contact braingate@ucdavis.edu.

Source: UC Davis Health

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Benefits of UV Exposure may Outweigh Risks in Low-sunlight Countries

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Photo by Julian Jagtenberg on Pexels

The health benefits of spending time in the sun could outweigh the risks for those living in areas with limited sunshine, a UK study suggests. In low-sunlight locations such as parts of the UK, exposure to higher levels of ultraviolet (UV) radiation was linked to a drop in deaths due to cardiovascular disease and cancer.

Adapting public health advice to reflect both the risks and benefits of UV exposure may help to reduce disease burden and improve life expectancy in low-sunlight countries, the research team says.

Experts caution that measures should still be taken to protect the skin when UV levels are high, to prevent sunburn and the development of skin cancer.

Volunteer data

University of Edinburgh scientists used genetic and health information from the UK BioBank – an anonymised database of health details from volunteers – to examine the UV exposure of 395 000 people across the UK. Participants were restricted to those of white European descent, due to the role skin pigmentation plays in the body’s response to UV exposure.

The team applied two measures to identify those exposed to higher levels of UV. They used the geographical location of participants to calculate their average annual exposure to solar energy and, separately, whether they used sunbeds.

The findings were adjusted for other factors that might influence health – including smoking, exercise, social deprivation and gender – to reduce the chance that these factors were responsible for any of the changes observed.

Health impact

Living in locations with higher UV levels, for example Cornwall, was associated with a lower risk of death from cardiovascular disease and cancer – 19% and 12%, respectively – than living in areas with lower UV levels, such as Edinburgh or Glasgow.

Sunbed use was linked to a 23% lower risk of death from cardiovascular disease and a 14% lower risk of death from cancer, compared to non-users. It is possible that people who use sunbeds may also seek out greater sun exposure and so this result may reflect broader sun seeking behaviour, the team says.

Those with a higher estimated UV exposure had a slightly increased risk of being diagnosed with melanoma, but their risk of dying from the condition was not raised.

As the study is based on UK data from a white European population, the findings are of most relevance to similar groups in low-sunlight countries. Further research into locations with higher UV exposure is needed to build a clearer picture of the potential benefits to health, experts say.

The study, funded by Health Data Research UK, is published in the journal Health and Place.

Our paper adds to a growing body of evidence suggesting that in lower light environments, relatively higher exposure to UV is good for your health. Though there may be an increased risk of skin cancer incidence with higher UV exposure, this risk appears to be outweighed by a larger reduction in the risk of death from cancer and cardiovascular related disease.

Professor Chris Dibben, University of Edinburgh’s School of GeoSciences

Dermatologists have traditionally only considered possible harm to the skin caused by sunlight, much of which dates from the experience of white-skinned individuals in sunny countries such as Australia. When the UV index is very high, protecting skin is important.

However, this research shows that in the UK, the balance of benefit and risk from sunlight exposure is probably very different from that in sunnier countries.

Professor Richard Weller, University of Edinburgh’s Centre for Inflammation Research

Source: The University of Edinburgh

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A New Way to Kill Cancer Cells via Ferroptosis

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Human colon cancer cells. Credit: National Cancer Institute

In a first, a team in Germany has produced a substance capable of sending cancer cells into ferroptosis, a form of cell death discovered only in recent years. This could pave the way for the development of new drugs.

Conventional cancer drugs work by triggering apoptosis, that is programmed cell death, in tumour cells. However, tumour cells have the ability to develop strategies to escape apoptosis, rendering the drugs ineffective. In the journal Angewandte Chemie, a research team from Ruhr University Bochum, Germany, describes a new mechanism of action that kills cancer cells through ferroptosis. Ferroptosis is another form of programmed cell death that wasn’t discovered until the 2010s. The Bochum group synthesised a metal complex, demonstrated its effectiveness in cell cultures and on microtumours and identified the chemical processes underlying the mechanism of action.

Two types of programmed cell death

In programmed cell death, certain signaling molecules initiate a kind of suicide program to cause cells to die in a controlled manner. This is an essential step to eliminate damaged cells or to control the number of cells in certain tissues, for example. Apoptosis has long been known as a mechanism for programmed cell death. Ferroptosis is another mechanism that has recently been discovered which, in contrast to other cell death mechanisms, is characterised by the accumulation of lipid peroxides. This process is typically catalysed by iron which is where the name ferroptosis derives from.

“Searching for an alternative to the mechanism of action of conventional chemotherapeutic agents, we specifically looked for a substance capable of triggering ferroptosis,” explains Johannes Karges. His group synthesized a cobalt-containing metal complex that accumulates in the mitochondria of cells and generates reactive oxygen species, more precisely hydroxide radicals. These radicals attack polyunsaturated fatty acids, resulting in the formation of large quantities of lipid peroxides, which in turn trigger ferroptosis. The team was thus the first to produce a cobalt complex designed to specifically trigger ferroptosis.

Effectiveness demonstrated on artificial microtumours

The researchers from Bochum used a variety of cancer cell lines to show that the cobalt complex induces ferroptosis in tumour cells. On top of that, the substance slowed down the growth of artificially produced microtumours .

“We are confident that the development of metal complexes that trigger ferroptosis is a promising new approach for cancer treatment,” as Johannes Karges sums up the research, adding: “However, there’s still a long way to go before our studies result in a drug.” The metal complex must first prove effective in animal studies and clinical trials. What’s more, the substance doesn’t currently selectively target tumour cells, but would also attack healthy cells. This means that researchers must first find a way to package the cobalt complex in such a way that it damages nothing but tumour cells.

Source: Ruhr-University Bochum

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Pesticide Use Within 500m of Pregnant Women Linked to Stillbirth Risk

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Photo by Arjun Mj on Unsplash

Living less than 500m from pesticide use prior to conception and during early pregnancy could increase the risk of stillbirths, according to new research published in the American Journal of Epidemiology.

Researchers from the University of Arizona found that during a 90-day pre-conception window and the first trimester of pregnancy, select pesticides, including organophosphates as a class, were associated with stillbirth.

“In this study, some specific ingredients stood out due to their significant associations with stillbirth risk,” said first author Melissa Furlong, PhD, who studies the chronic health effects of environmental contaminants as an assistant professor and environmental epidemiologist at the Zuckerman College of Public Health. “These findings underscore the importance of considering individual pesticides rather than just the overall pesticide class, as specific chemical compounds may pose unique risks. It also highlights the potential for pre-pregnancy exposures to affect reproductive outcomes.”

To conduct the study, researchers linked Arizona pesticide use records for 27 different pesticides with state birth certificate data that included 1 237 750 births and 2290 stillbirths from 2006 to 2020.

They found that living within 500m of specific pyrethroid, organophosphate or carbamate pesticide applications during a 90-day pre-conception window or the first trimester was associated with an increased risk of stillbirth. 

Specifically, the pesticides cyfluthrin, zeta-cypermethrin, organophosphates as a class, malathion, carbaryl and propamocarb hydrochloride were linked to increased stillborn births pre-conception. During the first trimester, fenpropathrin, permethrin, organophosphates as a class, acephate and formetanate hydrochloride were associated with stillbirths.

“Among organophosphates, acephate showed the strongest effect estimates on stillbirth, so that exposure to acephate in the first trimester was associated with a doubling of risk,” said co-author Paloma Beamer, PhD, a professor and interim associate dean at the Zuckerman College of Public Health.  “Within the pyrethroid class, cyfluthrin exposure during the 90 days prior to conception almost doubled the risk of stillbirth.”

Pesticides are chemical substances used to control pests in various settings. They are commonly categorized into different classes, such as organophosphates, pyrethroids and carbamates. The primary route of exposure for most people is through diet, but household use, agricultural drift and occupational exposure are also significant pathways.

Researchers say while some pesticides may not have been directly implicated in this study, they could still pose risks to maternal and foetal health.

Pregnant women may be particularly vulnerable to the adverse effects of pesticide exposure due to physiological changes during pregnancy, such as increased metabolic rate, altered hormone levels and changes in the immune system. The developing foetus may be more susceptible to the toxic effects of pesticides during this period of rapid growth and development.

“Further research is essential to fully understand the safety profiles of various pesticides and to understand the underlying mechanisms of pesticide-induced stillbirth,” Furlong said. “This study underscores the need to develop strategies for mitigating exposure to protect maternal and foetal health.”

Source: University of Arizona Health Sciences

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Early Sensorimotor Skill Differences can Guide Autism Diagnosis

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Photo by Helena Lopes on Unsplash

New research published in the journal iSCIENCE has revealed new insights into early sensorimotor features and cognitive abilities of toddlers who are later diagnosed with Autism Spectrum Disorder (ASD). The research, led by Kristina Denisova, a professor of Psychology and Neuroscience at the CUNY Graduate Center and Queens College, takes an important step toward better understanding ASD so that more precise, individually tailored interventions can be developed.

ASD, typically diagnosed around the ages of 4 to 5 years, is a neurodevelopmental disorder with complex and varied presentations, including atypical communication and restrictive and repetitive patterns of behaviour. Moreover, cognitive abilities are often lower in individuals with ASD. Despite the established link between lower intelligence quotient (IQ) in infancy and a future diagnosis of ASD, not all children with ASD exhibit lower cognitive abilities during infancy. The study addresses the critical gap in knowledge regarding the early features that differentiate children with varying cognitive abilities who later develop ASD.

The research team investigated the relationship between movement and cognitive abilities in toddlers before their ASD diagnosis, both during sleep and wakefulness. The study posed two key questions: Do ASD children with lower IQ exhibit altered movement during sleep compared to children with higher IQ? Additionally, are lower motor skills during wakefulness characteristic of lower-IQ children with ASD compared to those of higher-IQ ASD toddlers?

The research was conducted in two stages. In the first sample, the team examined sensorimotor features obtained from sleep functional magnetic resonance imaging (fMRI) in 111 toddlers with ASD. In the second, independent sample, they analysed sensorimotor functioning during wakefulness in over 1000 toddlers with ASD, categorised by lower vs higher cognitive abilities.

The findings revealed that toddlers with ASD and lower IQs have significantly altered sensorimotor features compared to toddlers with ASD and higher IQs. Interestingly, the sensorimotor features of higher-IQ ASD toddlers were nearly indistinguishable from typically developing (TD) toddlers. This suggests that a higher IQ may confer resilience to atypical sensorimotor functioning, and conversely, that poor sensorimotor functioning may be a key marker for lower IQ in childhood autism.

Moreover, the study found that lower-IQ ASD toddlers consistently exhibited lower gross motor skills across various age milestones (6, 12, 18, 24, and 30 months). This disruption in early sensorimotor learning during critical developmental periods indicates a potential vulnerability in the brain’s motor control circuitry, associated with lower cognitive abilities in toddlers who later receive an ASD diagnosis.

“The implications of these findings are far-reaching,” said Denisova. “They underscore the need for more precise, tailored interventions for children with ASD, particularly those with lower cognitive abilities. Interventions for lower-IQ autistic children may need to focus on enhancing both sensorimotor and cognitive skills, while interventions for higher-IQ autistic children might prioritise leveraging their strengths to mitigate potential mental health consequences.”

Denisova emphasised the importance of future research in this area, particularly involving underserved families who face barriers in accessing early intervention services.

Source: The Graduate Center, CUNY

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Kidney Damage in Lupus Comes from an Unexpected Source

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When the NKp46 receptor of the ILCs is blocked (right), the lupus nephritis recedes. Blue: cell nuclei.
Credit: Charité | Frauke Schreiber

A Berlin-led research team has uncovered critical regulators of severe kidney damage in patients with the autoimmune disorder lupus. A small, specialised population of immune cells – called innate lymphoid cells (ILCs) – trigger an avalanche of effects that cause harmful kidney inflammation, also known as lupus nephritis.

The research, published this week in Nature, upends conventional wisdom that autoantibodies are primarily responsible for lupus nephritis.

“While autoantibodies are required for tissue damage, they are by themselves not sufficient. Our work reveals that ILCs are required to amplify the organ damage,” says Dr Masatoshi Kanda, a senior paper author who was a Humboldt Fellow at Max Delbrück Center and is now at the Department of Rheumatology and Clinical Immunology, Sapporo Medical University in Japan.

Lupus, or systemic lupus erythematosus, is most often diagnosed between the ages of 15 and 45. Symptoms can range from mild to severe. But what causes kidney damage in some patients – some to the point of requiring dialysis – has been unclear.

“The role of ILCs in lupus or lupus nephritis was entirely unknown,” says Professor Antigoni Triantafyllopoulou, a senior paper author at the German Rheumatology Research Center (DRFZ), an institute of the Leibniz Association, and at the Department of Rheumatology and Clinical Immunology at Charité – Universitätsmedizin Berlin. “We have now identified most of the circuit controlled by ILCs by looking at the whole kidney at single-cell resolution.”

Unusual immune cells

ILCs are a small group of immune cells that – unlike most other immune cells that circulate throughout the body – live in a specific tissue or organ.

“They are in the tissue all the time, from the time of embryonic development, which makes them very different from other immune cells,” says Professor Andreas Diefenbach, a senior paper author and director of the Institute of Microbiology, Infectious Diseases and Immunology at Charité – Universitätsmedizin Berlin.

Diefenbach’s lab was among those that discovered ILCs in the mid-2000s. Most of his research is focused on ILCs in the gut and how they modify tissue function. In this study, Triantafyllopoulou and Kanda teamed up with his group and Dr Mir-Farzin Mashreghi at the DRFZ to find out whether ILCs were present in the kidney and what role they might play in lupus nephritis.

The whole single-cell picture

To unravel this mystery, the team turned to single-cell RNA sequencing, which identifies genes that are active, or “switched on,” in individual cells and helps researchers understand the cell’s identity and function.

Kanda, a rheumatologist who was studying bioinformatics in Professor Norbert Hübner’s lab at the Max Delbrück Center at the time, developed a specialized protocol for single-cell RNA sequencing of mouse and human kidneys. “Masatoshi’s protocol was very good at pulling out and preserving multiple types of kidney cells, which gave us a much more complete overview of how lupus affects the whole kidney,” explains Triantafyllopoulou. The team sequenced nearly 100 000 individual kidney and immune cells of various types and functions.

The key receptor

Through experiments in mice, the team learned that a subgroup of ILCs with a receptor called NKp46 must be present and activated to cause lupus nephritis. When NKp46 is activated, this subgroup of cells ramped up production of a protein called GM-CSF, which stimulates invading macrophages to multiply. In the kidney, a flood of incoming macrophages caused severe tissue damage and fibrosis.

“These ILCs are really amplifiers in this system,” Diefenbach says. “They are small in population, but they seem to fertilise the whole process.”

When the team blocked NKp46 with antibodies or the receptor was genetically removed, kidney tissue damage was minimal. They also blocked GM-CSF with similar anti-inflammatory effects.

“Critically, autoantibody levels did not change when NKp46 was inhibited, but kidney tissue damage was reduced, which shows autoantibodies are not directly responsible for kidney inflammation,” Triantafyllopoulou explains.

The team also compared the results to sequencing data from tissue taken from human patients with lupus and found ILCs present, though more work is required to fully understand how to target ILCs in human kidneys. Nevertheless, the insights gained through these detailed studies point to new antibody therapies for patients with severe forms of lupus. The hope is to prevent the need for kidney dialysis in these patients.

Source: Max Delbrück Center for Molecular Medicine in the Helmholtz Association

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Fight Not Yet over as Case Against Vertex is Dropped After Cystic Fibrosis Medicine Price Cut

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Cheri Nel launched a court case against Vertex to force them to allow their generic cystic fibrosis drug to be imported into South Africa. Credit: Spotlight

By Catherine Tomlinson

Last year a South African woman took a multibillion-dollar United States pharmaceutical company to court with the aim of securing access to life-changing cystic fibrosis medicines. That case has now been dropped following a reduction in the price charged for the medicines in South Africa.

Cheri Nel, a Johannesburg-based investment banker, has dropped a potentially landmark court case against Vertex Pharmaceuticals. Nel was asking the Gauteng Division of the High Court in Pretoria to grant a compulsory licence to allow generic versions of a cystic fibrosis medicine called Trikafta to be imported into South Africa. No such compulsory licences on medicines have ever been granted in South Africa.

Trikafta, which was registered in the United States in 2019, has been hailed as a “miracle” treatment for cystic fibrosis, which causes severe damage to the lungs, digestive system and other organs in the body. The medicine is effective in treating around 90 percent of people living with the condition. It significantly improves the quality of life of people living with cystic fibrosis, eliminating many of its debilitating symptoms, while also slowing the disease’s progression and extending survival.

In February 2023, when Nel launched her lawsuit against the Boston-headquartered pharmaceutical company, the only way people in South Africa could access Trikafta was by travelling to Argentina to buy it from an Argentinian company selling a generic version of the medicine.

This is because Vertex, the company that holds the patents on Trikafta in South Africa, refused to register the medicine with the South African Health Products Regulatory Authority (SAHPRA) or identify a local distributor that could import unregistered Trikafta via Section 21 authorisations – a mechanism allowing importation of unregistered medicines.

The United States list price for Trikafta is currently over $300 000 (around R5.5 million at the current rand/dollar exchange rate) per person per year, which South Africans feared they would also have to pay if or when Vertex finally started supplying its medicine in the country. Researchers in the United Kingdom have estimated that Trikafta can be produced for under $6000 (around R110 000 at the current rand/dollar exchange rate) per person per year.

When Nel filed the case, generic Trikafta from Argentina – called Trixacar – was much cheaper than Vertex’s product (but still prohibitively expensive for many) at around $60 000, or almost R1 million per person per year. But the Argentinian company selling generic Trixacar faced potential patent infringement challenges if it shipped Trixacar to South Africa. Thus, the only way to get the medicine into South Africa at the time was to travel to Argentina to collect it. People living with cystic fibrosis in South Africa learnt how to do this through an informal network or Buyers Club of people around the world that were reliant on the Argentinian product.

Launching a legal case

Nel argued that Vertex was abusing its patents in South Africa by refusing to make Trikafta available in the country on reasonable terms, while also blocking other manufacturers from supplying the medicine in the country. If successful, Nel’s case would have allowed generic Trikafta to be shipped directly to South Africa, removing the need for travel to Argentina to access the medicine.

According to Nel, Vertex argued in the company’s answering documents to her legal filing that, as she was the only named applicant in the case, a compulsory licence for importation could only be considered for her.

Nel then worked with the South African Cystic Fibrosis Association (SACFA) to get other people living with cystic fibrosis admitted as co-applicants in the case. This process of seeking more people to join her case, she said, was time-consuming, difficult, and expensive, but more than 100 people were working towards being admitted as co-applicants before the case was dropped.

Under pressure, Vertex starts providing Trikafta in South Africa

As the case gained momentum and made headlines around the world, Vertex finally opened the door to allow some people living in South Africa to access their product.

In May 2024, Vertex identified Equity Pharmaceuticals as the local company through which Trikafta could be imported into South Africa via Section 21 authorisations. These authorisations are granted by SAHPRA to enable importation of an unregistered medicine and are meant to be used in exceptional circumstances to remedy the need for an unregistered medicine, such as when there is a shortage of the registered product.

While Vertex has not confirmed to Spotlight or stated publicly the price of Trikafta for people living in South Africa, Nel and Doctors Without Borders’ Candice Sehoma told us that the company is charging around R400 000 ($22 000) for a year’s supply of the medicine.

While still unaffordable for many and much higher than the estimated cost of manufacturing, the R400 000 price is drastically lower than the R5.5 million price charged in the United States and originally feared for South Africa.

It seems improbable that Vertex would have offered the much reduced price to people living in South Africa had Nel not launched the court case

Some medical schemes now paying for Trikafta

As emerged in April this year, Vertex reached an agreement with some medical schemes in South Africa to provide the medicine for people on top-end plans.

“Four private healthcare providers are currently funding Trikafta for eligible patients and we are open for conversations with more insurance companies,” Vertex’s spokesperson Daria Munsel confirmed to Spotlight.

The exact nature of the conversations and/or agreements between Vertex and medical schemes in South Africa however remains somewhat unclear.

Discovery Health‘s CEO, Dr Ron Whelan, told Spotlight it has engaged Vertex about the “benefits available” and “affordable access” of the class of medications that Trikafta falls in but there is “no specific commercial agreement in place” in South Africa.

He noted that Discovery Health Medical Scheme members on the comprehensive and executive plans have a suite of benefits available for the treatment of cystic fibrosis with medicines like Trikafta “of up to R400 000 per annum” for eligible people.

According to Vertex, uptake of its product has been swift and is already starting to make a difference in the lives of people living with cystic fibrosis in South Africa. “Over 100 South Africans with CF [cystic fibrosis] have been prescribed our triple combination treatment in just the first two months of the medicine being available,” said Munsel.

The cystic fibrosis registry, an initiative which seeks to identify and collect data on the outcomes of people living with cystic fibrosis in South Africa, identified 525 people living with cystic fibrosis in the country as of December 2020. Experts believe there are many more undiagnosed cases.

Why did Nel drop the case?

Not only is Vertex’s price for people in South Africa now lower than the 2023 price of Argentinian generics, but the cost of a year’s supply of generic Trikafta from Argentina have increased from around $60 000 to around $100 000 due to hyperinflation in that country.

With Vertex now offering a price lower than the cost of Argentinian generics, Nel decided that her legal case was no longer the best avenue to enhance access to the medicine. The aim of the case “was to get access to the medication… to put pills in patients’ mouths”, she told Spotlight.

Nel said it is now probably better to redirect efforts to getting government at national or provincial levels to buy the medicine for patients in the public sector.

“There is a lot of work still to be done… my efforts are still there, it’s just being redirected,” she said.

“The fact that Trikafta will now be available in South Africa at a much lower price compared to generic versions globally, certainly undercuts the legal case for a compulsory license,” said Tendai Mafuma of SECTION27, a public interest law centre. The Treatment Action Campaign and Doctors Without Borders, represented by SECTION27, were admitted as friends of the court in the case.

Why won’t Vertex register its product in SA?

While much has changed because of Nel’s legal action, Vertex has held fast on its refusal to register Trikafta with SAHPRA.

When asked about Vertex’s plans to register Trikafta in South Africa, Munsel said: “We strongly believe that this [Section 21 Authorisation] is the fastest and most efficient route to sustainable access in South Africa, which does not require a regulatory filing.”

While registering medicines can be onerous and time consuming, it is a routine practice required for pharmaceutical companies to operate around the world. Full registration also typically requires that safety, effectiveness and quality is more closely scrutinised than is the case with Section 21 authorisations.

Nel believes that Vertex has chosen not to register Trikafta in South Africa because of the price transparency requirements embedded in South African law. If other countries know what price South Africa is paying then they may also demand a lower price, she said.

The law requires that there is a transparent pricing system for medicines sold in the private sector, but these requirements do not extend to unregistered medicines imported through Section 21 authorisations, explained Mafuma.

Note: SECTION27 was involved in the court case that is the subject of this article. Spotlight is published by SECTION27, but is editorially independent – and independence that the editors guard jealously. Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons licence.

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Categories : NeurologyTags : Leave a comment

Intracranial EEG Captures Neurons Resonating as They Turn Words into Thoughts

On By ModernMedia
The lines on this diagram of the brain represent connections between various areas of the cerebral cortex involved in language processing. When we read, the neurons in these areas fire in precise synchronicity, a phenomenon known as “co-rippling.” Photo credit: UC San Diego Health Sciences

Researchers at University of California San Diego School of Medicine have brought us closer to solving how the brain processes information from specialised areas into a whole. By delving into the brain with intracranial electroencephalography, they observed how neurons synchronise across the human brain while reading. The findings are published in Nature Human Behaviour and are also the basis of a thesis by UC San Diego School of Medicine doctoral candidate Jacob Garrett.

“How the activity of the brain relates to the subjective experience of consciousness is one of the fundamental unanswered questions in modern neuroscience,” said study senior author Eric Halgren, Ph.D., professor in the Departments of Neurosciences and Radiology at UC San Diego School of Medicine. “If you think about what happens when you read text, something in the brain has to turn that series of lines into a word and then associate it with an idea or an object. Our findings support the theory that this is accomplished by many different areas of the brain activating in sync.”

This synchronisation of different brain areas, called “co-rippling” is thought to be essential for binding different pieces of information together to form a coherent whole. In rodents, co-rippling has been observed in the hippocampus, the part of the brain that encodes memories. In humans, Halgren and his colleagues previously observed that co-rippling also occurs across the entire cerebral cortex.

To examine co-rippling at the mechanistic level, Ilya Verzhbinsky, an MD/PhD candidate completing his research in Halgren’s lab, led a study published in PNAS that looked at what happens to single neurons firing in different cortical areas during ripples. The present study looks at the phenomenon with a wider lens, asking how the many billions of neurons in the cortex are able to coordinate this firing to process information.

“There are 16 billion neurons in the cortex – double the number of people on Earth,” said Halgren. “In the same way a large chorus needs to be organised to sound as a single entity, our brain neurons need to be coordinated to produce a single thought or action. Co-rippling is like neurons singing on pitch and in rhythm, allowing us to integrate information and make sense of the world. Unless they’re co-rippling, these neurons have virtually no effect on the other, but once ripples are present about two thirds of neuron pairs in the cortex become synchronised. We were surprised by how powerful the effect was.”

Co-rippling in the cortex has been difficult to observe in humans due to limitations of noninvasive brain scanning. To work around this problem, the researchers used an approach called intracranial electroencephalography (EEG) scanning, which measures the electrical activity of the brain from inside the skull. The team studied a group of 13 patients with drug-resistant epilepsy who were already undergoing EEG monitoring as part of their care.

Participants were shown a series of animal names interspersed with strings of random consonants or nonsense fonts and then asked to press a button to indicate the animal whose name they saw. The researchers observed three stages of cognition during these tests: an initial hierarchical phase in visual areas of the cortex in which the participant could see the word without conscious understanding of it; a second stage in which this information was “seeded” with co-ripples into other areas of the cortex involved in more complex cognitive functions; and a final phase, again with co-ripples, where the information across the cortex is integrated into conscious knowledge and a behavioural response – pressing the button.

The researchers found that throughout the exercise, co-rippling (~100ms-long ~90Hz oscillations) occurred between the various parts of the brain engaged in these cognitive stages, but the rippling was stronger when the participants were reading real words.

The study’s findings have potential long-term implications for the treatment of neurological and psychiatric disorders, such as schizophrenia, which are characterised by disruptions in these information integration processes.

“It will be easier to find ways to reintegrate the mind in people with these disorders if we can better understand how minds are integrated in typical, healthy cases,” added Halgren.

More broadly, the study’s findings have significant implications for our understanding of the link between brain function and human experience.

“This is a fundamental question of human existence and gets at the heart of the relationship between mind and brain,” said Halgren. “By understanding how our brain’s neurons work together, we can gain new insights into the nature of consciousness itself.”

Source: University of California San Diego