A drug approved to treat eczema provided significant improvement in the symptoms of patients with severe itching diseases that currently have no targeted treatments, according to a new study published in JAMA Dermatology. The drug, abrocitinib, was found to cause minimal side effects during a small 12-week study led by University of Maryland School of Medicine (UMSOM) researchers. It was beneficial for those with an itching disease called prurigo nodularis as well as for those with chronic pruritus of unknown origin, a condition that causes chronic unexplainable itching symptoms.
“Very few treatments exist for prurigo nodularis and chronic pruritus of unknown origin; patients often suffer for years in horrible discomfort, which can lead to anxiety and depression, severely impacting their quality of life,” said Shawn Kwatra, MD, the Joseph W. Burnett Endowed Professor and Chair of Dermatology at UMSOM and Chief of Service Dermatology at the University of Maryland Medical Center (UMMC). “The rationale for this study came from my laboratory’s studies findings of altered inflammatory mediators in these conditions that all function through JAK1. Through this trial, we hope to continue to move the needle toward personalized therapies that can provide sustainable relief for coping with these debilitating conditions.”
Affecting at least 130,000 Americans, prurigo nodularis causes dozens of extremely itchy and disfiguring bumps, usually on the chest, arms, and legs. Dr. Kwatra’s previous research indicates that prurigo nodularis occurs more than 3 times as frequently in Black patients than white patients, tends to be more common in women, and is associated with depression, diabetes, chronic kidney disease, and HIV. Chronic pruritus of unknown origin is most prevalent among older adults and causes severe itching lasting longer than six weeks. Current therapies used to help manage symptoms include over-the-counter and prescription itch relief ointments and anti-inflammatory drugs such as antihistamines and corticosteroids. None of these medications, however, provide sustained relief.
The study involved a total of 20 patients, half of whom had prurigo nodularis and half of whom had chronic pruritus of unknown origin. They were all given a 200-milligram pill of abrocitinib once a day for 12 weeks; the patients knew they were being given an experimental treatment, and the study did not include a placebo group. Abrocitinib was found to reduce itching and pain symptoms by 78 percent in the prurigo nodularis patients. Patients with chronic pruritus of unknown origin experienced a 54 percent reduction in itching and pain symptoms. Patients in both groups also reported an improvement in their quality of life and in their sleep habits.
None of the patients experienced serious adverse events. The most common side effect, in 10 percent of patients, was small acne-like bumps.
Abrocitinib is a JAK1 inhibitor drug that works to suppress inflammation, specifically pro-inflammatory chemicals called cytokines that are involved in an overactive immune system. The drugs appear to slow down immune activity by suppressing intracellular signaling of these cytokines.
“This is not only an encouraging study but also sets the stage for a Phase 3 clinical trial,” said Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore. “It holds promise for introducing a novel treatment to patients in underserved communities disproportionately affected by prurigo nodularis, a condition historically overlooked by dermatology.”
Since beginning his position at UMSOM, Dr. Kwatra has created the Maryland Itch Center at UMMC and is currently continuing his research there.

How hard is it to stop taking antidepressants? If countless Internet posts and a number of scientific studies are to be believed, discontinuing these medications is highly problematic, and doctors often underestimate the difficulties involved. But it is unclear how common discontinuation symptoms actually are. Researchers from Charité — Universitätsmedizin Berlin and University Hospital Cologne have now conducted a systematic review and meta-analysis. In their article in The Lancet Psychiatry,* they conclude that one in three people reports symptoms after discontinuing antidepressant treatment, but half of those symptoms are attributable to negative expectations (the nocebo effect).
According to the formal definition, antidepressants are not habit-forming. Unlike “true” addictive substances, for example, taking them does not cause the body to require higher and higher doses to achieve the same effect. Even so, many patients report symptoms such as dizziness, headache, or insomnia when they stop taking these mood medications. The phenomenon went largely unremarked by researchers for years, but there are now a relatively large number of studies seeking to quantify the extent of discontinuation symptoms.
“The results of these studies vary, in some cases widely,” says Prof. Christopher Baethge, a researcher at the Department of Psychiatry and Psychotherapy at University Hospital Cologne and the Faculty of Medicine at the University of Cologne. “There has been a great deal of discussion, some of it quite emotional, within the research community and the general public alike in recent years about how prevalent and severe the discontinuation symptoms actually are.” A look at prescription figures shows just how relevant this topic is. According to the most recent Arzneiverordnungs-Report, which summarizes data on drug prescriptions, nearly 1.8 billion daily doses of antidepressants were prescribed in Germany in 2022.
Comprehensive meta-analysis brings clarity
To answer that question more reliably than before, a team led by Christopher Baethge and Dr. Jonathan Henssler, head of the Evidence-Based Mental Health research group at the Department of Psychiatry and Neurosciences at Charité, conducted a systematic review of existing studies and re-analyzed them in what is known as a meta-analysis. As the first study of its kind, it provides the soundest assessment to date of the consequences of stopping antidepressant treatment. “Our analysis shows that on average, one in three people will experience symptoms after stopping antidepressant treatment,” Henssler says. “However, only half of these symptoms are in fact attributable to the drug itself.”
For their paper, the researchers reviewed more than 6,000 studies. They then selected 79 of them and re-analyzed the results of those trials using statistical methods. In the end, they analyzed data on about 21,000 people, who had received either an antidepressant or a placebo and then been surveyed regarding the prevalence of discontinuation symptoms. Some 31 percent of the patients treated with an active drug reported discontinuation symptoms, but so did 17 percent of those who had received a placebo alone.
One in six or seven people experiences true discontinuation symptoms
“Drug effects can be ruled out in the placebo group, which means the symptoms either arose by chance, independently of the treatment, or they are the product of the nocebo effect,” Henssler explains. The nocebo effect is often considered the mirror image of the placebo effect. It explains the observation that inactive treatments can be associated with “side effects.” These effects are triggered purely by the expectation that the treatment that people think they are receiving will have negative effects.

“When we take non-specific symptoms and the effect of expectations into account, about one in six or seven people is affected by discontinuation symptoms that occur as an actual consequence of antidepressant medication,” Henssler says, summing up the study’s results. “In most cases, the symptoms are mild. The vast majority of those affected will be able to discontinue antidepressants without relevant symptoms. This means that in most cases, there is no need for a lengthy or gradual tapering process.”
Severe symptoms are rare
The study found that severe discontinuation symptoms are experienced by one in 35 people, or nearly three percent of those affected. These kinds of symptoms were more common after discontinuing treatment with the drugs imipramine, paroxetine, venlafaxine, and desvenlafaxine. There was not yet enough information on hand for the researchers to assess the situation for a number of widely used antidepressants.
As Baethge points out, “It’s important for all people wishing to discontinue treatment with antidepressants to be monitored and counseled by healthcare professionals and to receive individual support in the case of withdrawal symptoms. Joint decision-making between the patient and prescriber even before a course of treatment begins is the foundation of good treatment. We hope our data will support patients and healthcare professionals and help alleviate some of the uncertainty surrounding these issues today.”
About the study
The 79 studies considered in the meta-analysis included both randomized placebo-controlled trials and observational studies conducted without a control group. Of the 21,002 patients involved in the studies, 16,532 had received an antidepressant, and 4,470 a placebo. In addition to the researchers from Charité and University Hospital Cologne, researchers at the Medical Center — University of Freiburg and University Hospital Carl Gustav Carus, in Dresden, were involved in the meta-analysis.

Researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London have investigated the feasibility of a new home-administered treatment for binge eating disorder. The new treatment combines a gentle brain stimulation technique called transcranial direct current stimulation (tDCS) with a training programme that targets unhelpful patterns of attention around food.
The findings, published in BJPsychOpen, indicate that this might be a welcome new avenue for treatment.
Binge eating disorder (BED) is a serious mental illness that can affect anyone of any age, gender, ethnicity or background. People with the disorder have recurring episodes of losing control over their food intake, consuming lots of food in a short period of time until they are uncomfortably full. BED is typically accompanied by anxiety and low mood and linked to obesity and metabolic complications.
New approaches to meet an unmet need
Psychological therapies are recommended for treatment of BED and about 50 per cent of those who receive treatment achieve a full and lasting recovery.
Research has shown that self-regulatory processes in the brain are instrumental in maintaining the cycle of binge eating and innovative approaches such as tDCS and attention bias modification training (ABMT) aim to target these processes.
TDCS changes function in the prefrontal areas of the brain by applying a gentle electrical stimulation to carefully selected areas of the brain via electrodes placed on the scalp. ABMT improves self-regulatory control by correcting unhelpful biases towards food cues and training people with BED to change how they attend to high-calorie food cues.

TANDEM trial
New tDCS devices have been developed to enable self-administration at home. The TANDEM trial investigated whether the simultaneous delivery of at-home self-administered tDCS with ABMT is feasible, acceptable and potentially effective for the treatment of BED.
Researchers recruited 82 participants who were overweight or living with obesity and who met criteria for BED diagnosis. Participants were allocated to one of four groups that received either: 10 sessions of at-home self-administered tDCS during ABMT 10 sessions of pretend (sham) tDCS with a headset that did not deliver electrical stimulation during ABMT, 10 sessions of ABMT only, No treatment (they remained on a waitlist for 8 weeks).Less Binge Eating, Weight Loss and Mood improvements
Changes to binge eating behaviour were most pronounced in those who received real tDCS with ABMT. In this group binge episodes were reduced from around 20 times a month on average at baseline to six times a month at follow-up six weeks later.
Participants in the real tDCS with ABMT group also reported that they lost approximately 3.5 to 4 kg between baseline and six-week follow-up (reduction in mean body mass index [BMI] of 1.28 points). In comparison, over the same period time those who received ABMT with sham tDCS reported that they lost about 1.5 to 2 kg on average (reduction in mean BMI of 0.52 points) and those who received ABMT only reported negligible change in their weight (reduction in mean BMI of 0.07 points). There was no change in eating behaviour or weight loss in the no treatment control group.

The group who received real tDCS with ABMT also reported substantial improvement in their mood between baseline and follow-up. No similar change in mood was reported in those who received sham tDCS with ABMT or in those who received ABMT only, and there was no change in mood in the no treatment control.
Dr Michaela Flynn, Research Associateat King’s IoPPN, and first author on the study said: “Current treatments for binge eating disorder are only effective for some people and many need further or different support to get well. Our study is the first to look at a new option for home-based treatment that offers a different approach to treating binge eating disorder. TDCS targets the brain driven patterns of behaviour that might be contributing to the loss of control around food, enabling people to shift entrenched thinking and behaviour around food.
“Participants commented that their mood felt lighter, which may be a key part of why they reported changes in eating behaviour and weight loss that lasted for some time after treatment ended. Our findings are encouraging, and we want to explore this on a larger scale with more participants.”
Professor Ulrike Schmidt OBE, Professor of Eating Disorders at King’s IoPPN, aand coauthor said: “Binge eating disorder is a really neglected, but common and distressing eating disorder that is typically surrounded by a lot of shame. The treatment we tested is home delivered, which allows it to reach people who may find it difficult to come into the community. For some time eating disorder services have not been funded to work with or treat people with binge eating disorder. Importantly the treatment described here is straightforward to deliver making it potentially highly scalable in the NHS.”
Professor Iain Campbell, Senior Research Fellow at King’s IoPPN, said, “These encouraging clinical findings will help refine treatment protocols and promote studies of brain processes associated with neuromodulation. Future studies should verify these preliminary findings in a larger clinical trial which includes longer term follow-up beyond six-weeks. Additionally, the use of functional imaging and wearable technologies (which may provide insight into day-to-day changes in physical activity, food consumption, mood, and so on) might yield greater insight into the mechanism driving the therapeutic effects. Studies pairing tDCS with other treatments should also be considered such as mindfulness or other cognitive training techniques. ”
This research was supported by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC).

Healthcare providers should watch out for new and highly contagious forms of ringworm or jock itch, which are emerging as a potential public health threat, according to a pair of reports.
In the first of the studies, experts at NYU Langone Health who focus on the spread of contagious rashes document the first reported U.S. case of a sexually transmitted fungal infection that can take months to clear up even with treatment. In the second report, NYU Langone physicians partnered with authorities at the New York State Department of Health to describe the largest group of patients in the country with a similar fungal strain that resists standard therapies.
Both species of fungi are among a group that causes skin rashes, or tinea, that easily spread on the face and limbs (ringworm), groin (jock itch), and feet (athlete’s foot). However, the tinea explored in the new reports can look very different from the neat, regular circles seen in most forms of ringworm. They may instead be confused for lesions caused by eczema and can therefore go without proper treatment for months.
The first report, publishing online on June 5 in the journal JAMA Dermatology, describes a man in his 30s who developed tinea on his penis, buttocks, and limbs after returning home to New York City from a trip to England, Greece, and California. Genetic tests of fungal samples collected from the patient’s rashes revealed that the infection was caused by the species Trichophyton mentagrophytes type VII (TMVII). This sexually transmitted form of ringworm has been increasingly diagnosed throughout Europe, with 13 instances reported in France in 2023, mostly in men who have sex with men. Notably, the man in the current study said he had sex with multiple male partners during his travels, none of whom reported similar skin issues.
“Healthcare providers should be aware that Trichophyton mentagrophytes type VII is the latest in a group of severe skin infections to have now reached the United States,” said study lead author and dermatologist Avrom Caplan, MD. Caplan is an assistant professor in the Ronald O. Perelman Department of Dermatology at NYU Grossman School of Medicine.
“Since patients are often reluctant to discuss genital problems, physicians need to directly ask about rashes around the groin and buttocks, especially for those who are sexually active, have recently traveled abroad, and report itchy areas elsewhere on the body,” added study senior author John Zampella, MD.
Zampella, an associate professor in the Ronald O. Perelman Department of Dermatology at NYU Grossman says that while infections caused by TMVII are difficult to treat and can take months to clear up, they so far appear to respond to standard antifungal therapies such as terbinafine.

Meanwhile, Caplan says the new skin condition explored in his other new report presents a greater challenge for dermatologists. The study results, published online in May in JAMA Dermatology, center on Trichophyton indotineae (T. indotineae), which is widespread in India and is now reported globally. First confirmed to be in the U.S. last year, the infection causes similar itchy and contagious rashes as TMVII but often resists terbinafine treatment.
To better understand how T. indotineae can evade antifungal drugs, the researchers collected clinical and laboratory data from 11 men and women treated for ringworm in New York City hospitals between May 2022 and May 2023. Their tinea was confirmed to have been caused by T. indotineae. Seven of the patients had received standard doses of terbinafine for anywhere from 14 days (the usual duration for most forms of ringworm) to 42 days, yet their rashes did not improve.
Analyzing the fungal samples’ DNA, the team reported several variations in the genetic code (mutations) that prevent terbinafine from hooking onto fungal cells and poking holes in their protective membranes. According to the study authors, these mutations might help explain why the therapy often failed in some cases to fight the infections.
The results also showed that when seven patients were treated with another antifungal called itraconazole, three recovered entirely and two improved. The problem with this therapy however, Caplan says, is that while effective, the drug can interfere with many medications and can cause nausea, diarrhea, and other side effects that make it hard to use for long periods.
“These findings offer new insight into how some of the fungal skin infections spreading from South Asia can evade our go-to therapies,” said Caplan. “Beyond learning to recognize their misleading signs, physicians will need to ensure their treatment addresses each patient’s quality-of-life needs.”
Caplan adds that he plans to work with leading fungi experts around the U.S. and internationally over the next few months to expand research efforts and track emerging cases.
The researchers caution that while dermatologists should be on the alert for signs of TMVII and T. indotineae in their patients, rates so far remain low in the U.S.
Study funding was provided by NYU Langone.
In addition to Caplan and Zampella, other NYU Langone investigators involved in the TMVII study are Michelle Sikora, BS; Arianna Strome, MD; Christine Akoh, MD, PhD; and Caitlin Otto, PhD. Other study authors include Sudha Chaturvedi, PhD, at the New York State Department of Health in Albany.

Diabetes rates continue to rise, with 11.7 million Canadians living with diabetes or pre-diabetes. At UBC, scientists have created a pain-free drug delivery method to help people with diabetes manage the disease and maintain their health more easily.
Researchers at the Li Lab have developed oral insulin drops that when placed under the tongue are quickly and efficiently absorbed by the body, potentially replacing the need for insulin injections.
The drops contain a mixture of insulin and a unique cell-penetrating peptide (CPP) developed by Dr. Shyh-Dar Li and colleagues.
A little help from a peptide guide
“Insulin is a complicated molecule,” explains lead researcher Dr. Li, a professor in the faculty of pharmaceutical sciences. “In pill form, it’s easily destroyed in the stomach. Insulin also needs to be rapidly available in the blood, but as a large molecule, it cannot get through cells easily on its own.” The peptide, sourced from fish byproducts, opens a pathway for insulin to cross over.
Pre-clinical tests showed that insulin with the peptide effectively reaches the bloodstream whereas without the peptide, insulin remains stuck in the inside lining of the mouth.
“Think of it as a guide that helps insulin navigate through a maze to reach the bloodstream quickly. This guide finds the best routes, making it easier for insulin to get where it needs to go,” said Dr. Jiamin Wu, a postdoctoral researcher in the Li Lab.

Two versions of the peptide are described in recent articles in the Journal of Controlled Release (here and here). The UBC team is working to license the technology to a commercial partner.
Keeping medications on track
Healthy people get their insulin naturally from the pancreas to regulate glucose after a meal. Diabetes patients cannot produce sufficient insulin and need to get it from an outside source.
Unregulated glucose can be very dangerous, so diabetes patients must monitor their glucose levels and take insulin to lower it when necessary. While injections are the fastest way to get insulin into the blood, patients typically need at least three to four injections per day, which can affect their quality of life. Adherence to this regimen is challenging, and over time this can cause severe complications such as eye, kidney and nerve damage, potentially leading to limb amputations.
“My lab has been working on needle-free insulin alternatives these past three years,” said Dr. Li. “We tried nasal sprays before landing on oral drops, which are easy and convenient. Hopefully, the oral drops open up a new possibility for diabetes patients — making it easier to take their medications and regulate their blood glucose to maintain their health in the long run.”
Two inhalable insulin products (Exubera, Afrezza) were approved earlier but the effects were suboptimal and shown to increase the risk of lung cancer development. These products have been withdrawn. Dr. Li aims to achieve rapid, pain-free delivery of insulin without significant side effects. The new needle-free technology is expected to reduce the risk of cross-contamination, needle pricks, accidental infections and unsafe disposal of contaminated needles.

UCLA scientists have identified a protein that plays a critical role in regulating human blood stem cell self-renewal by helping them sense and interpret signals from their environment.
The study, published in Nature, brings researchers one step closer to developing methods to expand blood stem cells in a lab dish, which could make life-saving transplants of these cells more available and increase the safety of blood stem cell-based treatments, such as gene therapies.
Blood stem cells, also known as hematopoietic stem cells, have the ability to make copies of themselves via a process called self-renewal, and can differentiate to produce all the blood and immune cells found in the body. For decades, transplants of these cells have been used as life-saving treatments for blood cancers such as leukemia and various other blood and immune disorders.
However, blood stem cell transplants have significant limitations. Finding a compatible donor can be difficult, particularly for people of non-European ancestry, and the number of stem cells available for transplant can be too low to safely treat a person’s disease.
These limitations persist because blood stem cells that have been removed from the body and placed in a lab dish quickly lose their ability to self-renew. After decades of research, scientists have come achingly close to solving this problem.
“We’ve figured out how to produce cells that look just like blood stem cells and have all of their hallmarks, but when these cells are used in transplants, many of them still don’t work; there’s something missing,” said Dr. Hanna Mikkola, senior author of the new study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
To pinpoint the missing piece that prevents these blood stem cell-like cells from being fully functional, Julia Aguade Gorgorio, the paper’s first and co-corresponding author, analyzed sequencing data to identify genes that are silenced when blood stem cells are placed in a lab dish. One such gene, MYCT1, which encodes a protein by the same name, stood out as being essential to these cells’ self-renewal capacity.

They found that MYCT1 regulates a process called endocytosis, which plays a key role in how blood stem cells take in the signals from their environment that tell them when to self-renew, when to differentiate and when to be quiet.
“When cells perceive a signal, they have to internalize it and process it; MYCT1 controls how fast and how efficiently blood stem cells perceive these signals,” said Aguade Gorgorio, an assistant project scientist in the Mikkola lab. “Without this protein, the signals from the cells’ environment turn from whispers into screams and the cells become stressed out and dysregulated.”
The researchers compare MYCT1 to the sensors in modern cars that monitor all nearby activity and selectively relay the most crucial information to drivers at the right time, aiding decisions like when to safely turn or change lanes. Without MYCT1, blood stem cells resemble anxious drivers who, used to relying on these sensors, suddenly find themselves lost without their guidance.
Next, the researchers used a viral vector to reintroduce MYCT1 to see if its presence could restore blood stem cell self-renewal in a lab dish. Restoration of MYCT1, they found, not only made the blood stem cells less stressed and enabled them to self-renew in culture but also allowed these expanded cells to function effectively after being transplanted into mouse models.
As a next step, the team will investigate why the silencing of the MYCT1 gene occurs, and then, how to prevent this silencing without the use of a viral vector, which would be safer for use in a clinical setting.
“If we can find a way to maintain MYCT1 expression in blood stem cells in culture and after transplant, it will open the door to maximize all these other remarkable advances in the field,” said Mikkola, who is a professor of molecular, cell and developmental biology in the UCLA College and a member of the UCLA Health Jonsson Comprehensive Cancer Center. “This would not only make blood stem cell transplants more accessible and effective but also improve the safety and affordability of gene therapies that utilize these cells.”
This work was supported by the National Institutes of Health, the Swiss National Science Foundation, the European Molecular Biology Organization, the UCLA Jonsson Cancer Center Foundation, the James B. Pendleton Charitable Trust, the McCarthy Family Foundation, the California Institute for Regenerative Medicine, the UCLA AIDS Institute, the Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center, the Royal Society, the Wellcome Trust and the UCLA Broad Stem Cell Research Center Stem Cell Training Program.

Many people, especially children and the elderly, have difficulty swallowing pills. Liquid forms of many medicines taste extremely bitter and are often rejected. Put simply, strong bitterness is the main reason why people all over the world, especially children, avoid taking their medicines, putting their health, and sometimes, their lives at risk.
Now, a group of scientists at the Monell Chemical Senses Center identified the first temporary, universal taste blocker that works in people. Their findings appear in the British Journal of Pharmacology.
“Remarkably, and unlike our experience with blockers of bitter taste receptors, the taste-nerve blocker we tested worked for every subject and every bitter compound we tested,” said first author Linda J. Flammer, PhD, Monell Senior Research Associate and Director of the Corporate Partners Program. “I have never seen this before.”
Until now, efforts to block bitterness in foods and medicines have focused on finding blockers for bitter taste receptors on the tongue. Because different medications activate distinct sets of bitter taste receptors, targeting specific receptors may only suppress bitterness for certain, but not all, bitter-tasting compounds. “There is a clear need to develop bitter blockers that are able to suppress the bitterness of many medications,” said co-author Carol Christensen, PhD, Monell Alumnus Faculty Member. “Although humans have 25 different bitter receptors, our ongoing research suggests only a handful of bitter receptors may be responsible for most of the bitterness of medicines.”
Taste cells in the mouth that express the TAS2R family of taste receptors are stimulated by sweet, bitter, and savory compounds, and transmit signals to nerve fibers by releasing adenosine triphosphate (ATP), a cell’s main source of energy. In turn, ATP activates a receptor called P2X2/P2X3 on the receiving nerve cells. These nerves send information to the brain about the taste of foods and medications.
The team used an inhibitor of P2X2/P2X3 receptors, called AF-353, to block taste-nerve transmission and reduce the bitterness signal caused by medications and other taste compounds. Several blockers of P2X2/P2X3 receptors have been identified, with some tested in clinical trials to treat chronic cough; however, a side effect in these trials was taste disturbance. The Monell team capitalized on the “side effect” of these compounds to create an oral treatment that enhances the palatability of medicines.
A key finding of the study is that rinsing the mouth with AF-353 significantly reduced the bitterness of two important medicines that treat common chronic diseases: Praziquantel for parasites and Tenofovir Alafenamide (TAF) for hepatitis B and HIV.

“AF-353 is the first universal bitter taste blocker that has been identified,” said Monell Faculty Member Peihua Jiang, PhD. “In addition to bitter taste, it also affects savory, salt, sweet, and sour tastes. However, AF-353 only blocks taste. Other oral sensations like the tingle from carbonation were not affected.”
The team conducted both human sensory taste testing and mouse behavioral experiments to determine the breadth, strength, and duration of the blocking effects. The results of the human and rodent studies were similar in the breadth and duration of AF-353’s action.
The topical application of AF-353 directly into the mouth may improve compliance of many important medications, especially those that are life-saving for children in developing countries. “In people, the blocking effect lasted 60 to 90 minutes, when their taste was restored to normal,” said Flammer.
“We are now looking for taste blockers that act faster and allow taste to return to normal sooner,” said Jiang.orted by the Bill & Melinda Gates Foundation (INV-037008 and INV-042630). The behavioral work was performed at the Monell Behavioral and Physiological Phenotyping Core, which is supported, in part, by the National Institutes of Health (NIH) NIDCD Core Grant 1P30DC011735-01. Research infrastructure was provided in part by NIH Grant G20OD020296.

Researchers from the University of Colorado Anschutz Medical Campus have established a new framework for understanding how classic antidepressants work in treating major depressive disorder (MDD), reemphasizing their importance and aiming to reframe clinical conversation around their role in treatment.
The nature of the dysfunction at the root of MDD has been under investigation for decades. Classic antidepressants, like SSRIs (selective serotonin reuptake inhibitors, such as Prozac) cause an elevation in the levels of the brain chemical messenger, serotonin. This observation led to the idea that antidepressants work because they restore a chemical imbalance, such as a lack of serotonin. However, subsequent years of research showed no significant decrease in serotonin in people with depression. While experts have moved away from this hypothesis due to lack of concrete evidence, this has led to a shift in public opinion on the effectiveness of these medications.
Antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) are still effective in alleviating depressive episodes in many patients, however. In a paper published in Molecular Psychiatry, researchers outline a new framework for understanding how antidepressants are efficacious in treating MDD. This framework helps clarify how antidepressants like SSRIs are still be helpful, even if MDD isn’t caused by a lack of serotonin.
“The best evidence of changes in the brain in people suffering from MDD is that some brain regions are not communicating with each other normally,” says Scott Thompson, PhD, professor in the department of psychiatry at the University of Colorado School of Medicine and senior author. “When the parts of the brain responsible for reward, happiness, mood, self-esteem, even problem solving in some cases, are not communicating with each other properly, then they can’t do their jobs properly.
“There is good evidence that antidepressants that increase serotonin, like SSRIs, all work by restoring the strength of the connections between these regions of the brain. So do novel therapeutics such as esketamine and psychedelics. This form of neuroplasticity helps release brain circuits from being ‘stuck’ in a pathological state, ultimately leading to a restoration of healthy brain function,” said Thompson.
Thompson and colleagues liken this theory to a car running off the road and getting stuck in a ditch, requiring the help of a tow truck to pull the car out of its stuck state, allowing it to move freely down the road again.
Researchers are hoping health care providers will use their examples to bolster conversations with apprehensive patients about these treatments, helping them better understand their condition and how to treat it.
“We are hoping this framework provides clinicians new ways to communicate the way these treatments work in combating MDD,” said C. Neill Epperson, MD, Robert Freedman endowed professor and chair of the department of psychiatry in the University of Colorado School of Medicine and co-author on the paper. “Much of the public conversation around the effectiveness of antidepressants, and the role serotonin plays in diagnosis and treatment, has been negative and largely dangerous. While MDD is a heterogenous disorder with no one fits all solution, it is important to emphasize that if a treatment or medication is working for you, then they are lifesaving. Understanding how these medications promote neuroplasticity can help strengthen that message.”

As prostate cancer progresses, it becomes increasingly aggressive and can metastasise. In this form, the tumour is difficult to treat, which is reflected in high mortality rates: Worldwide, the malignant disease of the prostate is the second most common cause of cancer death in men. An international study led by Lukas Kenner (MedUni Vienna) and Sabine Lagger (Vetmeduni Vienna) has now identified a protein that could slow tumour growth. The results, which have just been published in the top journal “Molecular Cancer,” provide a new starting point for the development of therapies.
The complex molecular processes that lead to the progression of prostate cancer have not yet been fully clarified by science. The protein known as JUN is being intensively researched as a possible driver of tumour growth. “Numerous studies have shown that JUN is produced excessively in cancer. So, a link has been established between tumour growth and high JUN levels,” says Lukas Kenner (Clinical Institute of Laboratory Medicine at MedUni Vienna, Department of Laboratory Animal Pathology at Vetmeduni Vienna), explaining the background to the current study. In collaboration with national and international partners, it was shown that the opposite is the case with prostate cancer: the research team’s investigations using a mouse model and clinical samples revealed that the progression of prostate cancer is not accelerated but slowed down when JUN is present in high levels. On the contrary, it was observed that the tumour grows faster when the protein is missing.
The fact that JUN plays an important role in the activation of genes and various processes such as cell growth was discovered back in the 1980s. “In our investigations, we found that JUN is significantly involved in the regulation of prostate cancer by influencing the body’s immune response,” says Sabine Lagger from the Department of Laboratory Animal Pathology at Vetmeduni Vienna, explaining the connections currently being researched. If the protein is missing, the recruitment of certain immune cells in the tumour’s micro-environment is impaired, which leads to accelerated cancer growth. These results could explain why Prostate cancer is less responsive to immune therapy and could help to understand how to reactivate local immune responses.
Most common cancer in men
Prostate cancer has been the most common cancer in men in Austria for decades. Every year, around 6,000 new cases and 1,300 deaths are registered as a result of prostate cancer. In the vast majority of cases, tumours in the prostate gland remain localised and are therefore easily treatable. However, around 20 per cent of patients develop metastatic prostate cancer, which remains difficult to treat. “Our research suggests that activating JUN could potentially be a promising therapeutic option for slowing the progression of prostate cancer,” Sabine Lagger and Lukas Kenner summarise the significance of their study ahead of further investigations to confirm the results.

A novel gene therapy designed to target a form of inherited deafness restored hearing function in five children who were treated in both ears. The children also experienced better speech perception and gained the ability to localize and determine the position of sound. The study, the world’s first clinical trial to administer a gene therapy to both ears (bilaterally), demonstrates additional benefits than what were observed in the first phase of this trial, published earlier this year, when children were treated in one ear. The research was led by investigators from Mass Eye and Ear (a member of the Mass General Brigham healthcare system) and Eye & ENT Hospital of Fudan University in Shanghai, and findings were published June 5th in Nature Medicine.
“The results from these studies are astounding,” said study co-senior author Zheng-Yi Chen, DPhil, an associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear. “We continue to see the hearing ability of treated children dramatically progress and the new study shows added benefits of the gene therapy when administrated to both ears, including the ability for sound source localization and improvements in speech recognition in noisy environments.”
The researchers noted their team’s goal was always to treat children in both ears to achieve the ability to hear sound in three dimensions, a capability important for communication and common daily tasks such as driving.
“Restoring hearing in both ears of children who are born deaf can maximize the benefits of hearing recovery,” said lead study author Yilai Shu MD, PhD, professor, director of Diagnosis and Treatment Center of Genetic Hearing Loss affiliated with the Eye & ENT Hospital of Fudan University in Shanghai, “These new results show this approach holds great promise and warrant larger international trials.”
Over 430 million people around the world are affected by disabling hearing loss, of which congenital deafness constitutes about 26 million of them. Up to 60 percent of childhood deafness is caused by genetic factors. Children with DFNB9 are born with mutations in the OTOF gene that prevent the production of functioning otoferlin protein, which is necessary for the auditory and neural mechanisms underlying hearing.
This new study is the first clinical trial to use bilateral ear gene therapy for treating DFNB9. The new research presents an interim analysis of a single-arm trial of five children with DFNB9 who were observed over either a 13-week or 26-week period at the Eye & ENT Hospital of Fudan University in Shanghai, China. Shu injected functioning copies of the human OTOF transgene carried by adeno-associated virus (AAV) into the inner ears of patients through a specialized, minimally invasive surgery. The first case of bilateral treatment was conducted in July 2023. During follow-up, 36 adverse events were observed, but no dose-limiting toxicity or serious events occurred. All five children showed hearing recovery in both ears, with dramatic improvements in speech perception and sound localization. Two of the children gained an ability to appreciate music, a more complex auditory signal, and were observed dancing to music in videos captured for the study. The trial remains ongoing with participants continuing to be monitored.
In 2022, this research team delivered the first gene therapy in the world for DFNB9 as part of a trial of six patients in China treated in one ear. That trial, which had results published in The Lancet in January 2024, showed five of six children gained improvements in hearing and speech. Shu initially presented the data at the 30th annual congress of European Society of Gene and Cell Therapy (ESGCT) in Brussels, Belgium in October 2023, becoming the first in the world to report clinical data on using gene therapy to restore hearing.

“These results confirm the efficacy of the treatment that we previously reported on and represent a major step in gene therapy for genetic hearing loss,” said Shu. Shu trained under Chen for four years as a postdoctoral fellow at Mass Eye and Ear, with their collaboration continuing for more than a decade since he returned to Shanghai.
“Our study strongly supports treating children with DFNB9 in both ears, and our hope is this trial can expand and this approach can also be looked at for deafness caused by other genes or non-genetic causes,” added Chen, who is also an associate professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School. “Our ultimate goal is to help people regain hearing no matter how their hearing loss was caused.”
Currently, there are no drugs available to treat hereditary deafness, which has made room for novel interventions like gene therapies.
Mass General Brigham’s Gene and Cell Therapy Institute is helping to translate scientific discoveries made by researchers into first-in-human clinical trials. Chen and his colleagues are working with the Institute to develop platforms and vectors with good manufacturing practice standards that would enable his team to more easily test this therapeutic approach with other genes in the future.
The authors note that more work is needed to further study and refine the therapy. The bilateral study requires more consideration compared to the unilateral (one-ear) study as operations in both ears, in the course of one surgery, doubles the surgical time. Furthermore, by injecting double doses of AAVs into the body, the immune response is likely to be stronger and the potential for adverse effects could be greater. Looking ahead, more patients as well as a longer follow-up duration are necessary, and continued analysis of gene therapies and cochlear implants in larger randomized trials will be valuable.