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.
