One of the molecules responsible for triggering the inflammation that causes allergic respiratory diseases, such as asthma and allergic rhinitis, has just been discovered by scientists in France. This molecule, from the alarmin family, represents a therapeutic target of major interest for the treatment of allergic diseases. The study is published in the Journal of Experimental Medicine on 10 April.
The inflammation process plays a crucial role in allergic respiratory diseases, such as asthma and allergic rhinitis. Although the pulmonary epithelium is recognised as a major player in the respiratory inflammation that causes these diseases, the underlying mechanisms are still poorly understood.
The research team, from the CNRS, Inserm and the Université Toulouse III – Paul Sabatier and co-directed by Corinne Cayrol and Jean-Philippe Girard, has identified one of the molecules responsible for triggering these allergic reactions,. This molecule from the alarmin family, named TL1A, is released by lung epithelium cells a few minutes after exposure to a mould-type allergen.
It cooperates with another alarmin, interleukin-33, to alert the immune system.
This double alarm signal stimulates the activity of immune cells, triggering a cascade of reactions responsible for allergic inflammation.
Alarmins, therefore, constitute major therapeutic targets for the treatment of respiratory allergic diseases. In a few years’ time, treatments based on antibodies blocking the TL1A alarmin could benefit patients suffering from severe asthma or other allergic diseases.
The MOU between SAHPRA and Rwanda FDA will allow the regulators to develop a cooperative partnership towards ensuring access to safe, quality, and effective health products in the respective countries.
Areas of cooperation
SAHPRA and Rwanda FDA will cooperate in joint products reviews and inspections to enable efficient access to health products. The World Health Organization (WHO) has set up an initiative for establishing a mRNA technology transfer hub, together with six spokes, in Africa as a strategy to increase mRNA vaccine production capacity in under-served regions and thus promote regional health security. Rwanda is one of the spokes and South Africa being the hub. Thus, building on this model, SAHPRA and Rwanda FDA will collaborate in the area of mRNA vaccines regulatory oversight.
“The forging of partnerships with fellow African National Regulatory Authorities, namely the Rwanda Food and Drug Authority allows SAHPRA to further our drive in enhancing and building capacity on the continent,” says SAHPRA CEO, Dr Boitumelo Semete-Makokotlela.
“The signing of this MoU underscores the profound potential of collaboration among African NRAs, affirming that the solutions to our shared challenges lie within our continent. Rwanda FDA staunchly believes in the power of collaboration and strategic partnerships. This MoU symbolises the culmination of dedicated efforts and signifies our unwavering commitment to facilitating mutual exchange and enhancing regulatory oversight. Through collaborative efforts with SAHPRA, we aim to strengthen our regulatory capacity and promote public health. As we embark on this journey together, let us harness the collective strength of our agencies to advance the pharmaceutical sector in Rwanda and beyond,” shares Rwanda FDA Director-General, Professor Emile Bienvenu.
A new drug for the treatment of a type of brain tumour that strikes young people could soon receive approval by the U.S. Food and Drug Administration. The drug, vorasidenib, could greatly extend the time before further therapy – and eventual resistance – is needed.
In an editorial in the New England Journal of Medicine, David Schiff, MD, the co-director of UVA Cancer Center’s Neuro-Oncology Center, outlines the potential significance of the drug vorasidenib for patients with most low-grade gliomas. The drug was fast-tracked by the FDA in August 2023 based on the strength of the findings, and filings for regulatory approval were made in February 2024. FDA approval is anticipated in the second half of 2024, and its approval in Europe will likely soon follow.
Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumours. Of those, approximately 20% harbour an isocitrate dehydrogenase (IDH) mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas. Approximately 2500 Americans with a median age of only 40 are diagnosed with grade 2 IDH-mutant gliomas each year. The tumours cause steadily increasing disability, eventually become resistant to treatment options and typically prove fatal.
Because of the limited treatment options available, doctors usually take a “watch and wait” approach to managing the brain tumours, holding off on treatment until after the tumour progresses.
In the randomised controlled INDIGO trial, 331 patients received either vorasidenib or placebo. The trial showed that the drug slowed tumour growth significantly and extended the average time until the tumour started growing from 11.1 months to more than 27 months. Vorasidenib also increased the time to next intervention (TTNI), the timeframe before patients need additional treatment such as radio- or chemotherapy.
Schiff, in his editorial, describes the results as “striking.” Vorasidenib’s success could “put a nail in the coffin” of the watch-and-wait approach for such brain tumours, Schiff believes.
“It used to be that we thought of all gliomas as being on a spectrum,” Schiff said. “We now understand that those with the IDH gene mutation have a markedly different biology, outcome and, as this study shows, vulnerabilities that new therapies can exploit.”
If the drug receives approval from the federal Food and Drug Administration, it would become the first targeted therapy for low-grade gliomas. But Schiff notes that there are also other recent advances that are improving our understanding of such gliomas.
“There are still many unanswered questions about how we can best utilise this new medication if and when it receives FDA approval,” Schiff said. “Nonetheless, considering that existing standard therapies for these tumours [radiation and chemotherapy] are tough on patients, with short- and long-term side effects, it will be wonderful to have a useful and very well-tolerated treatment option.”
A neurosurgeon alleged during his employment tribunal that a “gang culture” exists within the neurosurgery department of an NHS hospital already beset by claims of a toxic culture and investigations into negligence.
As reported by the BBC, Dr Mansoor Foroughi was dismissed from University Hospitals Sussex in 2022 for misconduct. At a separate employment tribunal, Krish Singh, the former clinical director for general surgery, claimed that rota changes reduced the number of “safe” consultants, putting patients at risk.
Four whistleblowers had also told the BBC of a “Mafia-like” culture, where patients had died unnecessarily and others “maimed”. These new allegations came to light as the BBC and The Times fought a nine-month court battle to have the employment tribunal documents unsealed.
Dr Foroughi alleges that one colleague was signed off to do complex spinal procedures despite lacking training, another performed procedures with a “disproportionate” mortality rate, and yet another took on private work while on call to the NHS – a serious breach of conduct.
University Hospital Sussex encompasses several hospitals, which includes Royal Sussex Country Hospital, which has been the source of many complaints, and a history of poor service delivery, which was put into special measures between 2016 and 2019.
At least 105 cases of alleged medical negligence from failings at the hospital’s neurosurgery and general surgery departments are being investigated by police. According to court documents, there was “serious dysfunctionality in the neurosurgery department” with “stark divisions between colleagues”.
An investigation by the Royal College of Surgeons found that “a culture of fear” existed in the hospital’s surgery department, and that senior staff were “dismissive and disrespectful”. Two staff were allegedly assaulted.
In a statement, the trust said: “The trust will vigorously contest these claims at the Employment Tribunals, which we are keen take place at the earliest opportunity so they can be examined properly and fairly.
“Dismissing anyone, or removing someone from a leadership role, is an absolute last resort and we would always seek to avoid this outcome if possible.
“In both of these cases, due process was followed, and we are confident we did the right things, in the right way, for the benefit of our patients, their care and safety.”
A cystic fibrosis drug targeting the basic defect that causes the condition has been shown to be safe and effective in newborns aged four weeks and above, new research involving RCSI University of Medicine and Health Sciences and Children’s Health Ireland has found.
The finding is described as a “huge moment” for cystic fibrosis by one of the lead researchers. The study included the first baby in the world with cystic fibrosis to be diagnosed from birth and enrolled directly onto a trial of this sort.
The drug, ivacaftor (Kalydeko), is the first drug designed to treat the basic defect in cystic fibrosis. It was originally approved for adults, then sequentially over several years for older and younger children. Currently, it is approved for babies aged four months and older, however, this new research suggests that it is safe and effective for babies as young as four weeks of age.
Cystic fibrosis experts predict that the earlier treatments can begin, the more likely that progression of the condition can be slowed down or halted in children, and this is the focus of several international research studies led by RCSI and Children’s Health Ireland. The findings of this study could pave the way for eligible newborns to start treatment on the medicine at the time of diagnosis (typically at newborn screening) rather than having to wait until they are four months old.
“This is a huge moment in cystic fibrosis,” said Paul McNally, Associate Professor of Paediatrics at RCSI and Consultant in Respiratory Medicine at CHI. McNally is one of the authors of the new study which was published in the Journal of Cystic Fibrosis.
“Over the years ivacaftor, or Kalydeko, has been put through clinical trials in younger and younger children. Now, through this study, it has been shown to be safe and effective all the way down to four weeks of age,” he said.
“This is an important development because almost all children are diagnosed through newborn screening at around this time. The availability of a treatment that targets the underlying cause of the disease in newborns and can be started immediately at diagnosis will provide a huge sense of reassurance and hope for families.”
Cystic fibrosis is an inherited disease that mainly affects the lungs and digestive system. Ireland has the highest incidence of the condition in the world: approximately 1400 children and adults in Ireland live with the condition and more than 30 new cases of cystic fibrosis are diagnosed here each year, typically around four weeks of age through the newborn screening programme.
In recent years, new medicines have emerged that target the basic defect that causes cystic fibrosis. Ivacaftor (Kalydeko) is one such treatment. It targets a genetic change seen in around 4% of people with cystic fibrosis worldwide, and around 10% in Ireland.
Siblings Kara (aged 5) and Isaac Moss (aged 2) both participated in the study through Children’s Health Ireland. Kara was part of an earlier phase of the study that paved the approval of the drug in older infants and led to the latest trial that Isaac took part in.
Isaac was the first baby with cystic fibrosis in the world to be diagnosed from birth and enrolled directly onto a trial of these ground-breaking treatments.
“Both Kara and Isaac are doing really well and remarkably are not experiencing any of the typical symptoms of cystic fibrosis at the moment,” said their mother Debbie.
“Research studies like this one are so important to ensuring that children get access to the right treatments as early as possible. With the right medications, they can enjoy a healthy childhood and look forward to a brighter future”
Ivacaftor is manufactured by pharmaceutical company Vertex Pharmaceuticals, who are currently applying to the European Medicines Agency for an extension to the marketing authorization for Ivacaftor down to one month of age.
The study involved researchers from RCSI, Children’s Health Ireland, the U.S. and the UK.
Children and young people who are overweight or obese are at significantly higher risk of iron deficiency, according to a study by nutritional scientists at the University of Leeds.
Researchers from the School of Food Science and Nutrition examined thousands of medical studies from 44 countries involving people under the age of 25 where levels of iron and other vitamins and minerals had been recorded alongside weight. They found that iron deficiency was associated with both underweight and overweight children and adolescents.
By contrast, zinc and vitamin A deficiencies were only observed in children who were undernourished, leading researchers to conclude that iron deficiency in overweight children is probably due to inflammation disrupting the mechanisms that regulate iron absorption.
The results of the research appear in the journal BMJ Global Health.
Iron deficiency in children has a negative effect on brain function, including attention, concentration and memory, and can increase the risk of conditions, such as autism and ADHD.
It is already recognised as a problem in adults living with obesity, but this research is the first to look at the association in children.
Lead author Xiaomian Tan, a Doctoral Researcher in the University of Leeds’ School of Food Science and Nutrition said: “The relationship between undernutrition and critical micronutrients for childhood growth and development is well established, but less is known about the risk of deficiencies in iron, vitamin A and zinc in children and adolescents who are overweight or obese, making this a hidden form of malnutrition.
“Our research is hugely important given the high prevalence of obesity in children. We hope it will lead to increased recognition of the problem by healthcare practitioners and improvements in clinical practice and care.”
Hidden hunger
Historically the problem has been linked to malnutrition and is a particular concern for lower- and middle-income countries where hunger may be the leading cause of mortality for young children.
Increasingly though it is being recognised that vitamin and mineral deficiencies can also occur in people who are overweight and obese and who have a nutrient-poor but energy-dense diet, something which has been described as ‘hidden hunger’.
In high-income countries it is associated with ultra-processed foods that are high in fat, sugar, salt, and energy but in lower- and middle-income countries obesity is often associated with poverty and monotonous diets with limited choices of staples such as corn, wheat, rice, and potatoes.
Many developing countries are now facing a double burden of malnutrition alongside overnutrition due to the rapid increase in the global prevalence of obesity in recent decades, especially in children aged between five and 19.
Undernutrition versus overnutrition
The research also highlights differences in focus between higher income countries and developing nations, with most studies in Africa and Asia focusing on undernutrition and those from North America and Europe focusing entirely on overnutrition.
The researchers say this is particularly concerning as both Africa and Asia are experiencing the highest double burden of malnutrition due to economic growth and the transition to a western-style high-sugar, high-fat diet.
Between the years 2000 and 2017, the number of overweight children under the age of five in Africa increased from 6.6 to 9.7 million, and in Asia that figure rose from 13.9 to 17.5 million. At the same time, there was an increase in the number of stunted children under 5, from 50.6 to 58.7 million in Africa.
Research supervisor Bernadette Moore, Professor of Nutritional Sciences in Leeds’ School of Food Science and Nutrition, said: “These stark figures underscore the fact that the investigation of micronutrient deficiencies in relation to the double burden of malnutrition remains critically important for child health.
“By the age of 11 here in the UK, one in three children are living with overweight or obesity, and our data suggests that even in overweight children inflammation leading to iron deficiency can be an issue.
“Iron status may be the canary in the coalmine, but the real issue is that prolonged inflammation leads to heart disease, diabetes and fatty liver.”
Increasing physical activity and improving diet have been shown to reduce inflammation and improve iron status in children and the researchers are now calling for further studies into the effectiveness of these interventions.
They also believe that more research is needed into micronutrient deficiencies and the double burden of malnutrition and overnutrition in countries where there are currently gaps in data.
Colourised transmission electron micrograph of hepatitis B virus particles (colourised red and yellow). Credit: NIAID and CDC (Transmission electron micrograph image courtesy of CDC; colourisation by NIAID).
Over 12 million people worldwide suffer from a chronic infection with the hepatitis D virus. This most severe viral liver disease is associated with a high risk of dying from liver cirrhosis and liver cancer. It is caused by the hepatitis D virus (HDV), which uses the surface proteins of the hepatitis B virus (HBV) as a vehicle to specifically enter liver cells via a protein in the cell membrane – the bile salt transporter protein NTCP. This cell entry can be prevented by the active agent bulevirtide.
An international research team has now succeeded in deciphering the molecular structure of bulevirtide in complex with the HBV/HDV receptor NTCP at the molecular level. The research results published in the journal Nature Communications pave the way for more targeted and effective treatments for millions of people chronically infected with HBV/HDV.
The entry inhibitor bulevirtide is the first and currently only approved drug (under the drug name Hepcludex) for the treatment of chronic infections with the hepatitis D virus. The active agent effectively inhibits the replication of hepatitis D viruses and leads to a significant improvement in liver function. But the exact mechanism by which bulevirtide interacts with the virus entry receptor on the surface of the liver cells – the bile salt transporter protein NTCP (sodium taurocholate cotransporting polypeptide) – and thereby inhibits the entry of the viruses into the cells was previously unknown.
In order to understand the molecular interaction of bulevirtide and NTCP at the molecular level, the researchers first generated an antibody fragment that specifically recognises the NTCP-bulevirtide complex and makes it accessible for analysis when bound to nanoparticles. This complex was then analysed using cryo-electron microscopy, which allowed to visualise structural details with atomic resolution. The research results represent a milestone in understanding both the interaction of HBV and HDV with their cellular entry receptor NTCP and the mechanism of cell receptor blockade by bulevirtide.
How bulevirtide blocks the cell entry receptor NTCP
The analysis showed that bulevirtide forms three functional domains in the interaction with the HBV/HDV receptor NTCP: a myristoyl group that interacts with the cell membrane on the outside of the cell; an essential core sequence (‘plug’) that fits precisely into the bile salt transport tunnel of the NTCP like the bit of a key into a lock; and an amino acid chain that stretches across the extracellular surface of the receptor, enclosing it like a brace.
“The formation of a ‘plug’ in the transport tunnel and the associated inactivation of the bile salt transporter is so far unique among all known virus-receptor complexes. This structure explains why the physiological function of the NTCP is inhibited when patients are treated with bulevirtide,” says Prof Stephan Urban, DZIF Professor of Translational Virology and Deputy Coordinator of the DZIF research area Hepatitis, in whose laboratory at Heidelberg University the active agent bulevirtide was developed.
“Thanks to the structural details of the interaction with bulevirtide, we have also gained insights that enable the development of smaller active agents – so-called peptidomimetics – with improved pharmacological properties. Our structural analysis also lays the foundation for the development of drugs that are not only based on peptides and possibly enable oral administration,” adds the co-author of the study, Prof Joachim Geyer from the Institute of Pharmacology and Toxicology at Justus Liebig University Giessen.
Evolutionary adaptation of hepatitis B viruses to host species
The structural analysis also helped to decode an important factor in the species specificity of hepatitis B and D viruses. According to the findings of the analysis, the amino acid at position 158 of the NTCP amino acid chain plays an essential role in virus-receptor interaction. A change in the amino acid at this position prevents the binding of HBV/HDV. This explains why certain Old World monkeys, such as macaques, cannot be infected by HBV/HDV.
“Our findings enable a deeper understanding of the evolutionary adaptation of human and animal hepatitis B viruses to their hosts and also provide an important molecular basis for the development of new and targeted drugs,” adds co-author Prof Dieter Glebe, DZIF scientist at the Institute of Medical Virology at Justus Liebig University Giessen.
“Thanks to the structural details of the interaction with bulevirtide, we have also gained insights that enable the development of smaller active agents — so-called peptidomimetics — with improved pharmacological properties. Our structural analysis also lays the foundation for the development of drugs that are not only based on peptides and possibly enable oral administration,” adds the co-author of the study, Prof Joachim Geyer from the Institute of Pharmacology and Toxicology at Justus Liebig University Giessen.
Evolutionary adaptation of hepatitis B viruses to host species
The structural analysis also helped to decode an important factor in the species specificity of hepatitis B and D viruses. According to the findings of the analysis, the amino acid at position 158 of the NTCP amino acid chain plays an essential role in virus-receptor interaction. A change in the amino acid at this position prevents the binding of HBV/HDV. This explains why certain Old World monkeys, such as macaques, cannot be infected by HBV/HDV.
“Our findings enable a deeper understanding of the evolutionary adaptation of human and animal hepatitis B viruses to their hosts and also provide an important molecular basis for the development of new and targeted drugs,” adds co-author Prof Dieter Glebe, DZIF scientist at the Institute of Medical Virology at Justus Liebig University Giessen.
The disciplinary hearing against “anti-vax” doctor Shankara Chetty got underway in Durban this week, after changes to the charge sheet were made.
This comes after Chetty asked that the charges be dismissed or revised – or he would approach the high court for relief.
The charges are based on allegations by Francois Venter, a medical professor at Wits University who was at the forefront of Covid research in South Africa. He said Chetty was practicing “pseudo-science” at the height of the pandemic, with Chetty claiming that vaccines made no sense.
Chetty’s argument, in the main, focusses on his right to freedom of expression and claims that expressing a view is not a violation of the ethical guidelines of the Health Professions Council of South Africa (HPCSA).
His lawyers argued that the charges should have been dropped. Instead, the disciplinary committee ordered that they be amended.
The revised charge sheet contains four charges of unprofessional conduct.
They include that he contravened norms and standards by using unproven and unrecommended health technologies, namely Chetty’s “8th day” protocol, and that he failed to act in the best interests of patients by prescribing ivermectin, corticosteroids, and hydroxychloroquine for Covid, which were not approved by the South African Health Products Regulatory Council for this purpose.
He is also charged with casting aspersions on expert health care professionals who were authorised to provide advice and develop protocols, by stating that they engineered protocols in hospitals to “cause death and damage” to Covid patients.
The final, and fourth charge, is based on allegations that he “mischaracterised the cause and identification of the Covid illness, spike proteins and the toxicity of the virus”, which was not in line with the tenets of science.
In his complaint to the HPCSA, Venter said Chetty had made unprecedented claims in a video regarding the toxicity of Covid vaccines and that they were a “deliberate mass poisoning and planned to kill billions”.
He said Chetty, on his own website, had also made “outlandish physiological claims” which undermined the most basic tenets of accepted science about the vaccines, and advocated outpatient remedies of his own.
He said the video and the website “were more than enough evidence of gross misrepresentation of the vaccine programme: anybody watching would be justified in being severely alarmed at the prospect of mass poisoning”.
Chetty’s narrative, Venter said, went against the Department of Health, local experts, and international guidelines.
“This level of pseudo-science within the profession needs to be firmly and quickly clamped down on. The HPCSA must do its duty in protecting the public and discipline Chetty.”
In his written response, Chetty said the video was taken at a three-day Caribbean Summit held by the Word Council for Health, which brought together experts in various fields to share opinions and insights on the pandemic. (Wikipedia describes the World Council for Health as a pseudo-medical organisation dedicated to spreading misinformation to discourage COVID-19 vaccination and promoting fake COVID-19 treatments.)
The summit was not open to the general public and was a behind-closed-doors robust discussion.
Chetty said he did not consent to any recording being shared with the public.
He said he was not an “anti-vaxxer” but he was of the view that the vaccine technology had been rushed to market, with poor safety surveillance by clinical trials, and with a disregard for informed consent and individual choice.
In a written response, Venter said Chetty’s right to freedom of speech did not absolve him of his ethical duties.
This included not posting opinions on the professional reputations of their colleagues on social media “lest the public lose faith in the healthcare profession”.
Chetty is expected to plead not guilty to all the charges. According to the minutes of a pre-inquiry conference, both the HPCSA and Chetty intend to call expert witnesses.
A new review of research evidence has explored the key differences in how women and men sleep, variations in their body clocks, and how this affects their metabolism. Published in Sleep Medicine Reviews, the paper highlights the crucial role sex plays in understanding these factors and suggests a person’s biological sex should be considered when treating sleep, circadian rhythm and metabolic disorders.
Differences in sleep
The review found women rate their sleep quality lower than men’s and report more fluctuations in their quality of sleep, corresponding to changes throughout the menstrual cycle.
“Lower sleep quality is associated with anxiety and depressive disorders, which are twice as common in women as in men,” says senior author Dr Sarah L. Chellappa from the University of Southampton. “Women are also more likely than men to be diagnosed with insomnia, although the reasons are not entirely clear. Recognising and comprehending sex differences in sleep and circadian rhythms is essential for tailoring approaches and treatment strategies for sleep disorders and associated mental health conditions.”
The paper’s authors also found women have a 25 to 50% higher likelihood of developing restless legs syndrome and are up to four times as likely to develop sleep-related eating disorder, where people eat repeatedly during the night.
Meanwhile, men are three times more likely to be diagnosed with obstructive sleep apnoea (OSA). OSA manifests differently in women and men, which might explain this disparity. OSA is associated with a heightened risk of heart failure in women, but not men.
Sleep lab studies found women sleep more than men, spending around 8 minutes longer in non-REM (Rapid Eye Movement) sleep, where brain activity slows down. While the time we spend in NREM declines with age, this decline is more substantial in older men. Women also entered REM sleep, characterised by high levels of brain activity and vivid dreaming, earlier than men.
Variations in body clocks
The all-woman research ream from the University of Southampton in the UK, and Stanford University and Harvard University in the United States, found differences between the sexes are also present in our circadian rhythms.
They found melatonin, a hormone that helps with the timing of circadian rhythms and sleep, is secreted earlier in women than men. Core body temperature, which is at its highest before sleep and its lowest a few hours before waking, follows a similar pattern, reaching its peak earlier in women than in men.
Corresponding to these findings, other studies suggest women’s intrinsic circadian periods are shorter than men’s by around six minutes.
Dr Renske Lok from Stanford University, who led the review, says: “While this difference may be small, it is significant. The misalignment between the central body clock and the sleep/wake cycle is approximately five times larger in women than in men. Imagine if someone’s watch was consistently running six minutes faster or slower. Over the course of days, weeks, and months, this difference can lead to a noticeable misalignment between the internal clock and external cues, such as light and darkness.
“Disruptions in circadian rhythms have been linked to various health problems, including sleep disorders, mood disorders and impaired cognitive function. Even minor differences in circadian periods can have significant implications for overall health and well-being.”
Men tend to be later chronotypes, preferring to go to bed and wake up later than women. This may lead to social jet lag, where their circadian rhythm doesn’t align with social demands, like work. They also have less consistent rest-activity schedules than women on a day-to-day basis.
Impact on metabolism
The research team also investigated if the global increase in obesity might be partially related to people not getting enough sleep – with 30% of 30- to 64-year-olds sleeping less than six hours a night in the United States, with similar numbers in Europe.
There were big differences between how women’s and men’s brains responded to pictures of food after sleep deprivation. Brain networks associated with cognitive (decision making) and affective (emotional) processes were twice as active in women than in men. Another study found women had a 1.5 times higher activation in the limbic region (involved in emotion processing, memory formation, and behavioural regulation) in response to images of sweet food compared to men.
Despite this difference in brain activity, men tend to overeat more than women in response to sleep loss. Another study found more fragmented sleep, taking longer to get to sleep, and spending more time in bed trying to get to sleep were only associated with more hunger in men.
Both women and men nightshift workers are more likely to develop type 2 diabetes, but this risk is higher in men. Sixty-six per cent of women nightshift workers experienced emotional eating and another study suggests they are around 1.5 times more likely to be overweight or obese compared to women working day shifts.
The researchers also found emerging evidence on how women and men respond differently to treatments for sleep and circadian disorders. For example, weight loss was more successful in treating women with OSA than men, while women prescribed zolpidem may require a lower dosage than men to avoid lingering sleepiness the next morning.
Dr Chellappa added: “Most of sleep and circadian interventions are a newly emerging field with limited research on sex differences. As we understand more about how women and men sleep, differences in their circadian rhythms and how these affect their metabolism, we can move towards more precise and personalised healthcare which enhances the likelihood of positive outcomes.”
Early diagnosis is key to transformative treatment in Pompe disease
Photo by National Cancer Institute on Unsplash
15 April is recognised as International Pompe Day, a time dedicated to increasing awareness about Pompe Disease – a rare, inherited disorder that leads to progressive muscle and heart weakness. The day emphasises global awareness with the message: “Together We Are Strong.”
Pompe Disease is a condition resulting from mutations in a gene responsible for producing acid alpha-glucosidase (GAA), the enzyme necessary for breaking down glycogen, a sugar the body uses for energy.1 These mutations lead to a reduced or absent production of this enzyme, causing an accumulation of glycogen that damages muscles and the heart. The impact of the disease, including its severity and the age when symptoms appear, depends on how much the enzyme’s activity is reduced.1
Pompe Disease is classified into two types2: the infantile form, characterised by severe GAA deficiency and symptoms appearing in the first months of life1, and the late-onset form, where symptoms may start in childhood or adulthood, usually without affecting the heart.1
Early diagnosis is vital for managing Pompe Disease effectively and improving outcomes.2 Kelly du Plessis, CEO and Founder of Rare Diseases South Africa (RDSA), says: “The rise in adult diagnoses stresses the importance of recognising symptoms such as difficulty walking, frequent chest infections, fatigue, muscle weakness, and frequent falls. Symptoms in infants include feeding problems, poor weight gain, breathing difficulties, muscle weakness, an enlarged heart, floppiness, and delayed milestones.”1
Obtaining a Pompe Disease diagnosis can be challenging. Du Plessis’ own path to finding a diagnosis for her son confirms the difficulties of identifying Pompe Disease. “The journey to a diagnosis is fraught with complexity because of the many ways in which the disease presents. I urge parents to trust their intuition and seek medical counsel without delay, as early intervention is critical.”
Although there is no cure for the disease, Enzyme Replacement Therapy (ERT), available since 2006, supplies the body with a version of the GAA enzyme that people with Pompe Disease lack, and has significantly improved outcomes for patients.3
Monique Nel, Medical Advisor for Rare Diseases at Sanofi South Africa, emphasises the importance of early screening and treatment to prevent or minimise complications. “Access to ERT in South Africa has been life-changing for patients, offering improved energy levels and quality of life,” says Nel. “Starting ERT before the onset of symptoms can prevent or slow the progression of the disease. This means patients may experience fewer complications and a slower decline in their condition over time.”
Some of the key benefits of ERT include:
Improvement in muscle function: ERT helps to break down glycogen, preventing its harmful accumulation in muscle cells. Patients often experience improvements in muscle strength and function2, which can enhance mobility and daily living activities.
Enhanced respiratory function: Many individuals with Pompe Disease suffer from respiratory complications due to muscle weakness. ERT can lead to improved respiratory function2, reducing the need for ventilatory support and decreasing the frequency of respiratory infections.
Cardiac benefits: In the infantile form of Pompe Disease, heart enlargement and dysfunction are significant concerns. ERT has been shown to improve heart function2, which can be life-saving for infants affected by the disease.
“By addressing some of the primary symptoms of Pompe Disease, ERT can significantly improve the quality of life for patients,” says Nel. “This includes increased energy levels, reduced fatigue, and the ability to participate more fully in social, educational, and professional activities.”
“We also encourage healthcare professionals to consider Pompe Disease when evaluating patients with muscle weakness, respiratory issues, or unexplained cardiac symptoms, to ensure early diagnosis. Early diagnosis facilitates timely intervention and treatment, optimising patient outcomes and quality of life.”
1. National Institute of Neurological Disorders and Stroke. Pompe disease. N.d. Available at: https://www.ninds.nih.gov/health-information/disorders/pompe-disease#, accessed 9 April 2024. 2. Bhengu, L, et al. Diagnosis and management of Pompe disease. South African Medical Journal, 2014; 104(4):273-274. 3. Ficicioglu, C, et al. Newborn screening for Pompe disease: Pennsylvania experience. International Journal of Neonatal Screening, 2020; 6: 89.
