In a new study published in Molecular Biology of the Cell, a team of Rensselaer Polytechnic Institute researchers identified a previously unknown propofol anaesthetic mechanism, which, despite its frequent clinical application, is poorly understood.The study found that propofol exposure impacted the transportation of proteins to the surface of neurons, interrupting their function.
Almost all animal cells, including human cells, are highly compartmentalised and rely on efficient movement of protein material between compartments in vesicles. This transport must be efficient and highly specific to maintain cellular organisation and function.
The research team was led by Dr Marvin Bentley, associate professor at Rensselaer Polytechnic Institute, whose laboratory studies vesicle transport in neurons. Neurons are particularly reliant on vesicle transport because axons, often organised in nerve bundles. can span distances of up to 100cm in humans. Errors in vesicle transport have been linked to neurodevelopmental and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
This new study found that propofol affects a family of proteins called kinesins – small ‘motor proteins’ that move vesicles on tiny filaments called microtubules.
Dr Bentley’s team observed that vesicle movement of two prominent kinesins, Kinesin-1 and Kinesin-3, was substantially reduced in cells exposed to propofol. The team then showed that propofol-induced transport delays led to a significant drop in protein delivery to axons.
“The mechanism by which propofol works is not fully understood,” Bentley said. “What we discovered was unexpected: propofol altered the trafficking of vesicles in live neurons.”
Overall, the research contributes significantly to our understanding of how propofol works. Most studies on propofol’s anaesthetic mechanism have instead focused on its interaction with an ion channel called the GABAA receptor, which inhibits neurotransmission when activated.
This new study demonstrates that vesicle transport is an additional mechanism that may be important for propofol’s anaesthetic effect. Discovery of this new propofol effect has important applications for human health and may lead to the development of better anaesthetic drugs.
A recent study comparing atrial fibrillation (AF) treatments, published in The New England Journal of Medicine, shows that early intervention with cryoballoon catheter ablation (cryoablation) is more effective at reducing the risk of serious long-term health impacts, when compared to the current first step in treatment, antiarrhythmic drugs.
“By treating patients with cryoablation right from the start, we see fewer people advancing to persistent, more life-threatening forms of atrial fibrillation,” says Dr Jason Andrade, an associate professor of medicine at University of British Columbia. “In the short term, this can mean less recurrences of arrhythmia, improved quality of life and fewer visits to the hospital. In the long run, this can translate into a reduced risk of stroke and other serious heart problems.”
When used for AF, cryoablation is a minimally invasive procedure that involves guiding a small tube into the heart to kill problematic tissue by freezing. Historically, the procedure has been reserved as a secondary treatment when patients don’t respond to antiarrhythmic drugs.
“This study adds to the growing body of evidence that early intervention with cryoablation may be a more effective initial therapy in the appropriate patients,” says Dr Andrade.
Early intervention halts disease progression
AF affects approximately 3% of the population, and while the condition starts as an isolated electrical disorder, each recurring incident can cause electrical and structural changes in the heart that can lead to persistent AF, where episodes last more than seven days.
“Atrial fibrillation is like a snowball rolling down a hill. With each atrial fibrillation episode there are progressive changes in the heart, and the heart rhythm problem gets worse,” explains Dr Andrade.
The new findings, stemming from a multi-site clinical trial, show that cryoablation can stop this snowball effect.
Researchers enrolled 303 patients with AF in Canada. Half of the patients were randomised to receive antiarrhythmic drugs, while the other half were treated with cryoablation. All patients received an implantable monitoring device that recorded their cardiac activity throughout the study period.
At three years follow-up, patients in the cryoablation group were less likely to progress to persistent AF compared to patients treated with antiarrhythmic drugs. Over the follow-up period, the cryoablation patients also had lower hospitalisation rates and experienced fewer serious adverse health events that resulted in death, functional disability or prolonged hospitalisation.
Addressing the root cause
Because cryoablation targets and destroys the cells that initiate and perpetuate AF, the researchers say it can lead to longer-lasting benefits.
“With cryoablation, we’re treating the cause of the condition, instead of using medications to cover-up the symptoms,” says Dr Andrade. “If we start with cryoablation, we may be able to fix atrial fibrillation early in its course.”
The new study builds on previous work by Dr Andrade and colleagues demonstrating that cryoablation was more effective than antiarrhythmic drugs at reducing the short-term recurrence of atrial fibrillation.
Patients with nasopharyngeal cancer are often treated with immunotherapy. It was previously feared that, due to its immune response stimulation, COVID vaccination could reduce the success of cancer treatment or cause severe side effects. A recent study published as a “Letter to the editor” in the journal Annals of Oncology now gives the all-clear on this matter. What’s more, the study showed that cancer drugs actually worked better after vaccination with the Chinese vaccine SinoVac than in unvaccinated patients.
Many cancer cells are capable of subverting the body’s immune response. They do this by acting on the PD-1 receptor, they effectively shut down these endogenous defence forces. Drugs can be used to block PD-1 receptors. This enables the immune system to fight the tumour more effectively.
Vaccination against COVID also stimulates the immune response, involving the PD-1 receptor. “It was feared that the vaccine would not be compatible with anti-PD-1 therapy,” explains Dr Jian Li of the Institute of Molecular Medicine and Experimental Immunology (IMMEI) at the University Hospital Bonn. “This risk is especially true for nasopharyngeal cancer, which, like the SARS Cov-2 virus, affects the upper respiratory tract.”
Researchers from the Universities of Bonn and Shanxi in the People’s Republic of China investigated whether this concern is justified. More than 1500 patients treated in 23 hospitals from all over China participated in the analysis. Such multi-centre studies are considered to be particularly informative because the participants are very diverse and, moreover, the results are not distorted by regional characteristics.
Better response to cancer therapy
A subset of 373 affected individuals had been vaccinated with the Chinese COVID vaccine SinoVac. “Surprisingly, they responded significantly better to anti-PD-1 therapy than the unvaccinated patients,” explains Prof. Dr. Christian Kurts, Director of IMMEI. “Furthermore, they did not experience severe side effects more often.” The researchers cannot say why the treatment was more successful after vaccination. “We assume that vaccination activates certain immune cells, which then attack the tumor,” says Prof. Dr. Qi Mei of Shanxi University Hospital. “We will now investigate this hypothesis further.”
Nasopharyngeal cancer is quite rare in this country. In southern China and other countries in Southeast Asia, however, the disease is widespread. One of the suspected reasons for this is the frequent use of air conditioning in the hot and humid regions. Nutritional factors also appear to play an important role. In Taiwan, nasopharyngeal cancer is now considered one of the leading causes of death among young men.
Watching violent TV during the preschool years can lead to later risks of psychological and academic impairment by the end of primary school according to a new study published in the Journal of Developmental and Behavioral Pediatrics.
According to study leader Professor Linda Pagani, a professor at Université de Montréal’s School of Psycho-Education, it was previously “unclear to what extent exposure to typical violent screen content in early childhood – a particularly critical time in brain development – can predict later psychological distress and academic risks,” said Pagani.
“The detection of early modifiable factors that influence a child’s later well-being is an important target for individual and community health initiatives, and psychological adjustment and academic motivation are essential elements in the successful transition to adolescence,” she added.
“So, we wanted to see the long-term effect of typical violent screen exposure in preschoolers on normal development, based on several key indicators of youth adjustment at age 12.”
To do this, Pagani and her team examined the violent screen content that parents reported their children viewing between ages three-and-a-half and four-and-a-half, and then conducted a follow-up when the children reached 12.
Follow-up at age 12
At the follow-up, two reports were taken: first, of what teachers said they observed, and second, of what the children themselves, now at the end of Grade 6, described as their psychological and academic progress.
“Compared to their same-sex peers who were not exposed to violent screen content, boys and girls who were exposed to typical violent content on television were more likely to experience subsequent increases in emotional distress,” said Pagani.
“They also experienced decreases in classroom engagement, academic achievement and academic motivation by the end of the sixth grade,” she added.
“For youth, transition to middle school already represents a crucial stage in their development as adolescents. Feeling sadness and anxiety and being at risk academically tends to complicate their situation.”
Pagani and co-authors Jessica Bernard and Caroline Fitzpatrick came to their conclusions after examining data from a cohort of children born in 1997 or 1998 who are part of the Quebec Longitudinal Study of Child Development, coordinated by the Institut de la statistique du Québec.
Close to 2000 children studied
In all, the parents of 978 girls and 998 boys participated in the study of violent TV viewing at the preschool age. At age 12 years, the children and their teachers rated the children’s psychosocial and academic achievement, motivation and participation in classroom activities.
Pagani’s team then analysed the data to identify any significant link between problems with those aspects and violent content they were exposed to at preschool, while trying to account for as many possible biases and confounding influences as possible.
“Our goal was to eliminate any pre-existing conditions of the children or families that could have provided an alternative explanation or throw a different light on our results,” Pagani said.
Watching TV is a common early childhood pastime, and some of the children in the study were exposed to violence and some were not.
Psychological and academic impairment in children is of increasing concern for education and public-health sector workers. According to Pagani, problems starting middle school (ages 13 to 15) are rooted in early childhood.
Identifying with fictional characters
“Preschool children tend to identify with characters on TV and treat everything they see as real,” she said. “They are especially vulnerable to humorous depictions of glorified heroes and villains who use violence as a justified means to solve problems.
“Repeated exposure,” she added, “to rapidly paced, adrenaline-inducing action sequences and captivating special effects could reinforce beliefs, attitudes and impressions that habitual violence in social interactions is ‘ normal’. Mislearning essential social skills can make it difficult to fit in at school.”
Added Bernard: “Just like witnessing violence in real life, being repeatedly exposed to a hostile and violent world populated by sometimes grotesque-looking creatures could trigger fear and stress and lead these children to perceive society as dangerous and frightening.
“And this can lead to habitually overreacting in ambiguous social situations.”
She continued: “In the preschool years, the number of hours in a day is limited, and the more children get exposed to aggressive interactions (on screens) the more they might think it normal to behave that way.”
Pagani added: “Being exposed to more appropriate social situations, however, can help them develop essential social skills that will later be useful and ultimately play a key role in their personal and economic success.”
Women have a better ability to recover from kidney injury than men, but the reasons are not well understood. A study in Cell Reports may provide answers, as researchers found that females have an advantage at the molecular level that protects them from a newly discovered form of cell death that occurs in injured kidneys. This protection could be exploited as a potential therapeutic.
“Kidney disease afflicts more than 850 million people worldwide every year, so it’s important to understand why female kidneys are more protected from these acute and chronic injuries,” said Tomokazu Souma, MD, PhD, assistant professor at Duke University School of Medicine. “Our study is a step toward identifying the causes and suggests that this female resilience could be therapeutically harnessed to improve kidney repair in both sexes.”
Souma and colleagues conducted studies in mice focusing on a form of cell death called ferroptosis, which was only recently discovered. This form of cell death is dependent on iron and oxidative stress. It has been identified as a key player in kidney diseases.
Using genetic and single-cell RNA transcriptomic analysis in mice, the researchers found that being female confers striking protection against ferroptosis through a particular pathway called nuclear factor erythroid 2-related factor 2, or NRF2.
In females, NRF2 is highly active, keeping cell death in check. In males, however, the sex hormone testosterone reduces the activity of NRF2, thus promoting ferroptosis and undermining cell resiliency in kidney injury.
Further experiments showed that chemically activating NRF2 protected male kidney cells from ferroptosis, demonstrating that NRF2 could be a potential therapeutic target to prevent failed renal repair after acute kidney injury.
“By identifying the mechanism in which the female hormonal environment protects and the male hormonal environment aggravates acute and chronic kidney injuries, we believe there is strong potential to boost the resilience of kidneys,” Souma said.
Researchers have discovered that a certain hormone, that develops in males during puberty, could be predictive of the risk of developing age-related disease in later life.
The novel insulin-like peptide hormone, called INSL3, was found by researchers to be consistent over long periods of time and is an important early biomarker for prediction of age-linked disease. Their latest findings have been published today in Frontiers in Endocrinology.
INSL3 is produced in the testes by Leydig cells, which also make testosterone, but unlike testosterone which fluctuates over a man’s life, INSL3 remains consistent, with the level at puberty staying about the same throughout life, decreasing only slightly into old age. This makes it the first clear and reliable predictive biomarker of age-related morbidity as compared to any other measurable parameters.
Blood levels of INSL3 were associated with a range of age-related illnesses, such as bone weakness, sexual dysfunction, diabetes, and cardiovascular disease.
Since the hormone is so consistent, a young man with high INSL3 would still have high INSL3 when he is older. But low levels of INSL3 when young will stay low when older, making a man more likely to acquire typical age-related illnesses. This opens up exciting possibilities for predicting age-related illnesses and finding ways to prevent the onset of these diseases with early intervention.
This study from University of Nottingham was led by Professors Ravinder Anand-Ivell and Richard Ivell and is the latest of three recent studies into this hormone. Prof Anand-Ivell explains: “The holy grail of ageing research is to reduce the fitness gap that appears as people age. Understanding why some people are more likely to develop disability and disease as they age is vital so that interventions can be found to ensure people not only live a long life but also a healthy life as they age. Our hormone discovery is an important step in understanding this and will pave the way for not only helping people individually but also helping to ease the care crisis we face as a society.”
The team analysed blood samples from 3000 men, with two samples taken four years apart and found that unlike testosterone, INSL3 remains at consistent.
The study also showed that there is an almost 10-fold variation in INSL3 levels in the normal male population, even among the young and healthy.
Prof Ivell adds: “Now we know the important role this hormone plays in predicting disease and how it varies amongst men we are turning our attention to finding out what factors have the most influence on the level of INSL3 in the blood. Preliminary work suggests early life nutrition may play a role, but many other factors such as genetics or exposure to some environmental endocrine disruptors may play a part.”
The largest and most rigorous clinical trial to date of psilocybin (a psychoactive ingredient in magic mushrooms), suggests the possibility that COMP360 psilocybin with psychological support could be a beneficial therapeutic strategy for people with treatment-resistant depression (TRD). The trial results were published in the New England Journal of Medicine.
Prompted by promising preliminary findings, this funded multi-centre, randomised, double-blind, phase 2b clinical trial was launched in 2018 to determine the safety and potential antidepressant effects of a single dose of COMP360 psilocybin (25mg or 10mg), compared to 1mg, with psychological support in people with TRD.
The trial, which included 233 people with TRD across 10 countries who received a single dose of 25mg COMP360 psilocybin experienced a highly statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg at three weeks. This offers hope that COMP360 psilocybin with psychological support could be an effective antidepressant treatment paradigm for some people with TRD, if proven effective and safe in larger studies. COMPASS Pathways, the company that developed the psilocybin formulation., will be running a larger phase 3 programme of COMP360 psilocybin therapy in TRD, which is on schedule to begin in 2022.
KEY RESEARCH FINDINGS
25mg COMP360 psilocybin with psychological support led to a statistically and clinically significantly reduction in symptoms of depression in people with TRD compared to 1mg at week 3.
37% of people with TRD in the 25mg group met criteria for response at week 3 (≥ 50% decrease in depressive symptoms).
Approximately 30% of people with TRD in the 25mg group met criteria for remission at week 3 (29.1%).
20% of people with TRD in the 25mg group met criteria for sustained response at week 12.
COMP360 psilocybin was generally well-tolerated.
Dr John R. Kelly, Psychiatrist and Clinical Senior Lecturer, Trinity College said: “This is the largest and most rigorous clinical trial of psilocybin to date. It shows a promising antidepressant signal for 25mg COMP360 psilocybin with psychological support and has paved the way for phase 3 clinical trials, which will determine whether it translates into a much-needed complementary treatment strategy in the psychiatry clinic.”
Performing open bypass surgery to restore circulation for people with a severe form of peripheral artery disease (PAD) resulted in better outcomes for specific patients compared to a less-invasive procedure, according to findings published in the New England Journal of Medicine.
PAD is a condition in which blood flow to one or both legs is reduced by a buildup of fatty plaque in the arteries. One in 10 of patients with this condition develop a severe form of PAD called chronic limb-threatening ischaemia (CLTI), a painful and debilitating condition that can lead to amputation if untreated. Up to about 22 million people worldwide have CLTI, which is also associated with an increased risk of heart attack, stroke, and death.
“Given the projected rise in the number of patients with chronic limb-threatening ischaemia, it is critically important that we understand the full impact of our interventions for this disease,” said Matthew Menard, MD, a study author and associate professor of surgery and co-director of the endovascular surgery program at Brigham and Women’s Hospital, Boston. “These findings help do that and also can assist clinicians and caregivers in providing the best possible care to patients.”
The Best Endovascular versus Best Surgical Therapy for Patients with CLTI (BEST-CLI) trial is a landmark study supported by the National Heart, Lung, and Blood Institute (NHLBI).
To compare effectiveness of two common treatments for CLTI, researchers enrolled 1830 adults who were planning to have revascularisation, a procedure used to restore blood flow in their blocked arteries, and who were eligible for both treatment strategies.
One treatment strategy was an open bypass surgery, in which blood is redirected around the blocked leg artery by using a segment of a healthy vein. The other strategy was an endovascular procedure, where a balloon is dilated and/or a stent is placed in the blocked segment of the artery to improve blood flow. To compare the surgical strategy to the less-invasive endovascular approach, researchers randomised participants into one of two parallel trials between 2014–2021.
The first trial, defined as cohort 1, included 1434 adults who were judged to be the best candidates for the bypass surgery because they had an adequate amount of an optimal vein (the single-segment great saphenous vein) preferred for the procedure. Participants were then randomly assigned to have either a surgical bypass or endovascular procedure. Researchers followed the trial participants for up to seven years.
The second trial, defined as cohort 2, included 396 adults who were not the best candidates for the open bypass because they did not have an adequate amount of the preferred saphenous vein. They were randomised to have either an endovascular procedure or a bypass that used alternate graft material instead of the saphenous vein. Participants were followed-up for up to three years.
At the end of the trial, the researchers found that participants in cohort 1 who received the bypass were 32% less likely to have major medical events related to CLTI than those who had an endovascular procedure. This result was driven by a 65% reduction in major repeat surgeries or procedures to retain blood flow in the lower leg and a 27% reduction in major amputations. No differences were found in death rates between the participants who received the bypass surgery and those who received an endovascular procedure.
Adults in cohort 2 – those who did not have the optimal vein for the bypass – had no major differences in outcomes based on having had an open bypass or an endovascular procedure.
“Our findings support complementary roles for these two treatment strategies and emphasise the need for preprocedural planning to assess patients and inform what treatment is selected,” said co-principal investigator Alik Farber, MD, at Boston Medical Center.
Common symptoms of CLTI include leg and foot pain, foot infections, and open sores on the leg and foot that don’t fully heal. Without having a procedure to redirect or open blocked blood flow to the lower body, about 4 in 10 adults with CLTI have a lower leg or foot amputation.
BEST-CLI is the largest CLTI clinical trial to date and builds on prior research that aims to answer questions about the risks and benefits of revascularisation strategies for CLTI.
Inflammatory bowel disease is a risk factor for giving birth preterm even when in apparent disease remission, according to a study published in the journal eClinicalMedicine. If corroborated, the results may eventually affect recommendations for women with ulcerative colitis wishing to conceive.
Inflammatory bowel disease (IBD) is chronic inflammatory disease with a prevalence of approximately 0.5%. IBD, which includes ulcerative colitis and Crohn’s disease, and – unlike irritable bowel syndrome (IBS) – causes visible damage to the mucosa lining the intestines. IBD is characteristic for its recurrent tendency for symptoms to relapse, followed by periods of remission.
Onset of IBD commonly occurs at age 15–30, so questions about its impact on pregnancy and the foetus are common. IBD has previously been linked to negative birth outcomes, such as preterm birth (< 37 weeks of pregnancy), mainly in women showing signs of active disease.
Also, women without obvious IBD activity often have microscopic inflammation in the intestinal mucosa. Until now, however, it has been unknown whether even microscopic inflammation may be associated with risks in pregnancy.
Higher risk of preterm birth
The present study, shows that microscopic inflammation in IBD, especially ulcerative colitis, is linked to an elevated risk of giving birth prematurely.
Among babies born to women with microscopic inflammation due to IBD, 9.6% were preterm, while 6.5% of children were born preterm to women without microscopic inflammation of IBD. This corresponds to a relative risk increase of 46 percent. Microscopic inflammation was not clearly associated with other adverse pregnancy outcomes, such as growth restriction.
The results are based on register data on women in Sweden, diagnosed with IBD in 1990–2016, in whom information was available on the microscopic appearance of the intestine shortly before pregnancy. The study included 1223 children of women with microscopic IBD inflammation of the intestine and 630 children of women with IBD but with microscopically healed intestinal mucosa.
Through register linkages, data were also retrieved from several national health registers, such as the Swedish Medical Birth Register and the Swedish Quality Register for Inflammatory Bowel Desiease (SWIBREG).
Prospectof new treatment targets
“Our results suggest that IBD treatment aimed at not merely alleviate symptoms of IBD, but also microscopically heal the intestine, can reduce the risk of giving birth preterm,” sayd first author and corresponding author is Karl Mårild, associate professor of paediatrics at Sahlgrenska Academy, University of Gothenburg. “If our results hold up in future studies, they may therefore be the basis for recommendations to confirm microscopic healing before pregnancy, to reduce such risks.”
“Even a modestly increased relative risk of preterm birth is important, given that preterm birth can greatly affect the child’s health in both the short and the long term. Preterm birth is still one of the most common causes of death for children under the age of five in Sweden,” Karl Mårild concludes.
One dose of a new monoclonal antibody safely protected healthy, non-pregnant adults from malaria infection during the malaria season in Mali. The antibody was up to 88.2% effective at preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region. These findings were published in The New England Journal of Medicine.
The only WHO-recommended vaccine against vaccine, RTS,S (Mosquirix), provides partial protection against clinical malaria during the early years of life when given to children aged 5 to 17 months in four doses over a 20-month period. Other drugs consisting of small chemical compounds that effectively prevent malaria infection are also available for infants and young children as well as travellers. The requirement for frequent dosing of these drugs can limit adherence, however, and the emergence of drug resistance may also limit their usefulness. Thus, there is an urgent need for new, fast-acting, infrequently dosed interventions that safely provide strong protection against malaria infection.
Malaria is caused by Plasmodium parasites, which mosquitos inject into into the skin and bloodstream in a form called sporozoites. These travel to the liver, where they mature and multiply before spreading throughout the body via the bloodstream to cause illness. P. falciparum is the Plasmodium species most likely to result in severe malaria infections, which, if not promptly treated, may lead to death.
The Phase 2 NIAID-USTTB trial evaluated the safety and efficacy of a one-time, intravenous infusion of a monoclonal antibody called CIS43LS. This antibody was previously shown to neutralise the sporozoites of P. falciparum in the skin and blood before they could infect liver cells. Researchers led by Robert A. Seder, MD, isolated a naturally occurring form of this antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to extend the length of time it would remain in the bloodstream.
The study team for the Phase 2 trial enrolled 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where intense P. falciparum transmission typically occurs from July through December each year.
The first part of the trial assessed the safety of three different intravenous doses of CIS43LS – 5mg/kg of body weight, 10 mg/kg and 40 mg/kg – in 18 study participants, with six participants per dose level. The study team followed these participants for 24 weeks and found the antibody infusions were safe and well-tolerated.
The second part of the trial assessed the efficacy of two different doses of CIS43LS compared to a placebo. Three hundred and thirty participants were assigned at random to receive either 10mg/kg of the antibody, 40mg/kg, or a placebo by intravenous infusion. No one knew who was assigned to which group until the end of the trial. The study team followed these individuals for 24 weeks, testing their blood for P. falciparum weekly for the first 28 days and every two weeks thereafter. Any participant who developed symptomatic malaria during the trial received standard treatment from the study team.
The investigators analysed the efficacy of CIS43LS two ways. Based on the time to first P. falciparum infection over the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective at preventing infection and the lower dose (10 mg/kg) was 75% effective. An analysis of the proportion of participants infected with P. falciparum at any time over the 24-week study period found the high dose was 76.7% at preventing infection and the lower dose was 54.2% effective.
“These first field results demonstrating that a monoclonal antibody safely provides high-level protection against intense malaria transmission in healthy adults pave the way for further studies to determine if such an intervention can prevent malaria infection in infants, children, and pregnant women,” Dr Seder said. “We hope monoclonal antibodies will transform malaria prevention in endemic regions.”
Dr Seder and colleagues have developed a second antimalarial monoclonal antibody, L9LS, that is much more potent than CIS43LS and therefore can be administered in a smaller dose as a more convenient subcutaneous injection. An early-phase NIAID trial of L9LS in the United States found that the antibody was safe and prevented malaria infection for 21 days in 15 out of 17 healthy adults exposed to P. falciparum in a carefully controlled setting. Two larger, NIAID-sponsored Phase 2 trials assessing the safety and efficacy of L9LS in infants, children and adults are underway in Mali and Kenya.
