Publisher Health

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has demonstrated the safety and tolerability of a new drug treatment designed as a therapeutic intervention for spinal cord injury (SCI).
The research, published in British Journal of Clinical Pharmacology, found that the KCL-286 drug — which works by activating retinoic acid receptor beta (RARb) in the spine to promote recovery — was well tolerated by participants in a Phase 1 clinical trial, with no severe side effects. Researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI.
Global prevalence of SCI is estimated to be between 0.7 and 1.2 million cases per year, with falls and road accidents being the major causes. Despite incurring a cost of $4 billion per year in direct healthcare and indirect costs (i.e. inability to work and social care) in the US alone, there are no licensed drugs that can tackle the intrinsic failure of the adult central nervous system to regenerate, and thus remains a largely unmet clinical need.
Previous research by various groups has shown that nerve growth can be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist1, was developed by Professor Corcoran and team and used in a first in man study to test its safety in humans.
109 healthy males were divided into one of two trial groups; single ascending dose (SAD) adaptive design with a food interaction (FI) arm, and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments.
SAD studies are designed to establish the safe dosage range of a medicine by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects, and measure how the medicine is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to accumulate within the body.
Researchers found that participants were able to safely take 100mg doses of KCL-286, with no severe adverse events.

Over the past decade, the gut microbiome has gained significant interest by scientists and non-scientists alike. Recent research has shown that the bacteria and other microbes in our gut play a supporting role in immunity, metabolism, digestion, and the fight against “bad bacteria” that try to invade our bodies.
However, new research published in Nature Biotechnology by Angela Wahl, PhD, Balfour Sartor, MD, J. Victor Garcia, PhD, and UNC School of Medicine colleagues others has revealed that the microbiome may not as always be protective against human pathogens.
Using a first-of-its-kind precision animal model with no microbiome (germ-free), researchers have shown that the microbiome has a significant impact on the acquisition of Epstein-Barr virus (EBV) and human immunodeficiency virus-1 (HIV) infection and plays a role in the course of disease.
“These findings offer the first direct evidence that resident microbiota can have a significant impact on the establishment and pathology of infection by two different human-specific pathogens,” said Wahl, assistant professor in the Division of Infectious Diseases in the UNC Department of Medicine.
This research was conducted through a collaboration with scientists at the UNC International Center for the Advancement of Translational Science and the Division of Gastroenterology and Hepatology at the UNC School of Medicine.
For the discovery to be made, Wahl and Garcia needed to create a “humanized” mouse model that mimicked a human’s immune system to conduct their study. Once exposed to a virus, the humanized models can replicate the virus like a human and could be used for study.
But researchers needed to take it one step further. Wahl and Garcia needed to compare a conventional humanized mouse model to one without a microbiome (germ-free). This meant that they needed to create a first-of-its-kind mouse model that was humanized and free of bacteria.

Two distinct neurodevelopmental abnormalities that arise just weeks after the start of brain development have been associated with the emergence of autism spectrum disorder, according to a new Yale-led study in which researchers developed brain organoids from the stem cells of boys diagnosed with the disorder.
And, researchers say, the specific abnormalities seem to be dictated by the size of the child’s brain, a finding that could help doctors and researchers to diagnosis and treat autism in the future.
The findings were published Aug. 10 in the journal Nature Neuroscience.
“It’s amazing that children with the same symptoms end up with two distinct forms of altered neural networks,” said Dr. Flora Vaccarino, the Harris Professor in the Child Study Center at Yale School of Medicine and co-senior author of the paper.
Using stem cells collected from 13 boys diagnosed with autism — including eight boys with macrocephaly, a condition in which the head is enlarged — a Yale team created brain organoids (small, three-dimensional replicas of the developing brain) in a lab dish that mimic neuronal growth in the fetus. They then compared brain development of these affected children with their fathers. (Patients were recruited from clinician colleagues at the Yale Child Study Center, which conducts research, service, and training to improve understanding of health issues facing children and their families.)
The study was co-led by Alexandre Jourdon, Feinan Wu, and Jessica Mariani, all from Vaccarino’s lab at the Yale School of Medicine.
About 20% of autism cases involve individuals with macrocephaly, a condition in which a child’s head size is in the 90th percentile or greater at birth. Among autism cases these tend to be more severe.

A research team led by The Hong Kong University of Science and Technology (HKUST) has developed a novel technique to self-assemble a thin layer of amino acids with ordered orientation over a large area that demonstrates high piezoelectric strength, making the manufacturing of biocompatible and biodegradable medical microdevices, such as pacemaker and implantable biosensor, in the near future possible.
The generation of bioelectricity from the piezoelectric effect — reversible conversion between mechanical and electrical energies — has physiological significance in living systems. Piezoelectric charges generated by the human tibia during walking boost bone remodeling and growth. Also, piezoelectric potential in the lungs generated during respiration could assist in binding oxygen to hemoglobin.
Currently, most of the piezoelectric materials are rigid, brittle and some of them even contain toxic materials like lead and quartz, making them unsuitable for implantation in the human body. Piezoelectric biomaterials such as amino acids are promising alternatives since they naturally exhibit biocompatibility, reliability, and sustainability. However, manipulating biomolecules at scale with an aligned orientation for functioning correctly has been proven difficult and remained an international academic challenge for 80 years.
Addressing the long-standing challenge, a team led by Prof. Zhengbao YANG, Associate Professor in the Department of Mechanical and Aerospace Engineering at HKUST, recently developed an active self-assembly strategy to tailor piezoelectric biomaterial thin films via synergistic nanoconfinement and in-situ poling. It enables biomolecules to self-assemble over a very large area with the same orientation. More importantly, based on this novel technique, the team found that films of a kind of amino acid, β-glycine, exhibit an enhanced piezoelectric strain coefficient of 11.2pmV−1, which is the highest compared to the other biomolecular films.
Their self-assembled piezoelectric biomolecular films are capable of producing electrical signals from mechanical stress produced by muscle stretching, breathing, blood flow and small body movements. With no batteries required, they will simply dissolve in the body when their mission is complete.
Prof. Yang said, “Our study shows uniformly high piezoelectric response and excellent thermostability across the entire β-glycine films. The excellent output performance, natural biocompatibility, and biodegradability of the β-glycine nanocrystalline films are of practical implications for high-performing transient biological electromechanical applications, such as implantable biosensor, wireless charging power supply for bioresorbable electronics, smart chip and other biomedical engineering purposes.”
The team will continue to examine ways in improving the film’s flexibility to match biological tissues, and achieving low-cost mass production of the bioresorbable piezoelectric films. They are also looking to conduct experiments in animals, to demonstrate biomedical applications in vivo.
This study is a collaborative work with City University of Hong Kong and University of Wollongong in Australia. The research findings were recently published in Nature Communications.

Atherosclerosis is a disease in which fat, cholesterol, and other substances build up inside artery walls. This can lead to plaque formation, which can block arteries and cause heart attacks and strokes. Immune cells play a key role in cleaning the blood, by interacting with red blood cell extracellular vesicles (RBCEVs), which are nano-sized particles released by red blood cells.
Commonly referred to as “first responders” to infections, macrophages are immune cells which detect and clear pathogens and dead cells, and secrete molecules to activate other immune cells. To understand what happens to macrophages that are exposed to a high amount of RBCEVs and whether they prove to be beneficial in treating atherosclerosis, a multi-institutional team examined the mechanisms of how RBCEVs are internalised by macrophages and analysed the consequent changes.
Led by Assistant Professor Minh Le from the Department of Pharmacology and the Institute for Digital Medicine (WisDM), Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), the study demonstrated that the uptake of RBCEVs by macrophages was highly efficient, as the particles induced multiple changes in the macrophages. Following exposure to RBCEVs, the macrophages had decreased levels of proteins that promote inflammation, suggesting the potential use of RBCEVs to alleviate conditions associated with excessive inflammation. The macrophages also produced higher levels of an enzyme which protects cells against oxidative damage — commonly observed in inflammatory and cardiovascular diseases. In addition, the RBCEVs led to higher resistance to lipid uptake in the macrophages, reducing fat deposition — which characterises the condition of atherosclerosis.
Published in the Journal of Extracellular Vesicles, one of the top Cell Biology journals, the study was conducted in collaboration with the Department of Surgery, Department of Physiology, Nanomedicine Translational Research Programme, and Cardiovascular Research Institute at NUS Medicine; the School of Mechanical and Aerospace Engineering and Lee Kong Chian School of Medicine, Nanyang Technological University (NTU); and the Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR).
Asst Prof Minh Le said, “We have known for a while that RBCEVs tend to go to macrophages when they enter the body, but we did not realise some of the implications until now. The properties of RBCEVs that we have uncovered here are desirable for treating atherosclerosis and possibly other inflammatory diseases.”
The team hopes to leverage their improved understanding to manipulate RBCEV uptake by macrophages and thus adjust the distribution of RBCEVs to different tissues in the body. The team also plans to further explore the therapeutic potential of RBCEVs by combining their natural beneficial properties with exogenously loaded drugs designed to treat inflammatory conditions. These plans are part of the expansion of their ongoing work on developing the RBCEV platform for the treatment of various diseases including cancer, cancer-associated muscle loss, and COVID-19.
“Atherosclerosis causes heart disease and stroke, affecting millions of people. This discovery by the team is paving the way towards exciting new therapeutic strategies that can have a real impact on healthcare. We can now start looking into the use of very tiny particles made from our own red blood cells to treat atherosclerosis and potentially other diseases,” said Professor Lee Chuen Neng from the Department of Surgery, and Nanomedicine Translational Research Programme at NUS Medicine. He is also Clinical Director, Institute for Health Innovation & Technology, NUS.

Unlike previously thought, speech production and singing are supported by the same circuitry in the brain. Observations in a new study can help develop increasingly effective rehabilitation methods for patients with aphasia.
The neural network related to speech is mostly located in the left cerebral hemisphere, while singing has been primarily associated with the structures of both hemispheres. However, a new study indicates that the left hemisphere has a greater significance, including in terms of singing, than previously thought.
“According to a notion prevalent for more than 50 years, the potential preservation of singing ability in aphasia is based on the fact that the right hemisphere of the brain offers, as it were, a detour to expressing sung words,” says Doctoral Researcher Anni Pitkäniemi from the University of Helsinki.
This theory has also served as a basis for the development of singing-based rehabilitation strategies for patients with aphasia, or difficulty producing speech due to cerebrovascular disease.
However, a recently published study carried out by the Cognitive Brain Research Unit at the University of Helsinki found that, contrary to the researchers’ expectations, the ability to produce words by singing was associated not with the structures of the right hemisphere, but, as with speech, with the language network of the left hemisphere.
Both shared and distinct neural connections
Another key finding in the study was that, while the results indicate that the production of speech and singing are centrally linked to the language network of the brain, they are partially dispersed into distinct circuits under that network.

Restaurants can persuade patrons to choose healthier foods by adjusting the font size of numbers attached to nutritional information on menus, according to a study headed by a Washington State University researcher.
Lead researcher Ruiying Cai, an assistant professor in the WSU School of Hospitality Business Management, said U.S. restaurants with more than 20 locations are already required to show the calorie content of food on their menus. By representing these values incongruously — using physically larger numbers on the page when they’re attached to lower-calorie options, and smaller numbers for high-calorie foods — Cai said businesses can successfully “nudge” customers toward healthier choices.
“When restaurants use a larger font size for the calorie content of healthy foods, even though the number itself has a smaller value, it will increase consumers’ preference to order the healthier item,” Cai said.
For the study, recently published in the International Journal of Hospitality Management, participants were asked to choose between a less healthy item like a smoked beef burger and a healthier option like a grilled chicken sandwich. They were then randomly assigned to two groups. In the first group, number values and font size rose and fell together. In the second group, the relationship between the numbers’ magnitude and their size was incongruent, meaning the font size became smaller as the number values rose and vice versa.
Researchers also posed questions to gauge how health-conscious participants were and gave varying time limits to some to measure the effect time constraints have on their decisions. Cai said the study results showed that participants in second group, who saw low calorie counts printed in large fonts, were more likely to lean toward the healthier option. Respondents who indicated they were less health-conscious were also the most affected, particularly when there was a tight timeframe to make the choice.
People who had a high level of health awareness were less likely to be swayed, Cai said, but this is likely because they already favored healthy food.
“Even if you use some of the smart tricks, it does not work as well as for those who are not so knowledgeable about health,” Cai said.

Researchers at the University of Bristol have made a remarkable step forward in finding a potential cure for a type of childhood kidney disease.
The research project has shown that just one dose of gene therapy targeting cells in the kidney has the potential to cure a condition known as steroid-resistant nephrotic syndrome.
The research project received early funding from charity Kidney Research UK and the Wellcome Trust and has gone on to gain further support from Purespring Therapeutics.
The findings, which were published in the journal Science Translational Medicine by the team in Bristol led by Professor Moin Saleem, from the Bristol Medical School, suggested that replacing one faulty gene that codes for a protein known as podocin could cure the condition. Podocin is a protein essential for the functioning of cells called podocytes which have a critical role within the kidney’s filtration system.
Nephrotic syndrome is a condition where the kidney’s filtering units are damaged, allowing large amounts of protein that should be kept in the bloodstream to leak into the urine. This can lead to swelling, particularly in the eyes and legs, and an increased risk of infections and blood clots, and the risk of kidney damage. It can occur at any age but is most commonly diagnosed in children under five years old.
Often the symptoms can be managed with a type of medication known as steroids, however, around 10% of children with nephrotic syndrome do not respond to steroids and many will go on to develop kidney failure and will need dialysis or transplant within two to five years. This is the group where a faulty gene is frequently the cause of the disease.
Professor Saleem said:”We are hoping that this treatment could be curative. You keep the same podocytes for life, so if we can change their gene expression right at the beginning of the disease, we should be able to prevent this disease from progressing. With most kidney diseases, there is a reasonable window of opportunity, often years, before you get irreversible damage to the kidneys, where we would hope to be able to intervene with gene therapy and avoid the need for dialysis or transplantation.”
The discovery could bring major benefits to hundreds of children who currently suffer from nephrotic syndrome. If the intervention works, patients will be saved from a life of kidney failure and subsequent dialysis and transplant treatments.

New research from The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has successfully reversed hearing loss in mice.
The research, published in Proceedings of the National Academy of Sciences, used a genetic approach to fix deafness in mice with a defective Spns2 gene, restoring their hearing abilities in low and middle frequency ranges. Researchers say this proof-of-concept study suggests that hearing impairment resulting from reduced gene activity may be reversible.
Over half of adults in their 70s experience significant hearing loss. Impaired hearing is associated with an increased likelihood of experiencing depression and cognitive decline, as well as being a major predictor of dementia. While hearing aids and cochlear implants may be useful, they do not restore normal hearing function, and neither do they halt disease progression in the ear. There is a significant unmet need for medical approaches that slow down or reverse hearing loss.
Researchers in this study bred mice with an inactive Spns2 gene. Mice were then provided with a special enzyme at differing ages to activate the gene after which their hearing improved. This was found to be most effective when Spns2 was activated at a young age, with the positive effects of gene activation becoming less potent the longer the researchers waited to provide the intervention.
Professor Karen Steel, Professor of Sensory Function at King’s IoPPN and the study’s senior author said, “Degenerative diseases such as progressive hearing loss are often believed to be irreversible, but we have shown that at least one type of inner ear dysfunction can be reversed. We used a genetic method to show this reversal as a proof-of-concept in mice, but the positive results should encourage research into methods like gene therapy or drugs to reactivate hearing in people with a similar type of hearing loss.”
Dr Elisa Martelletti, the study’s first author from King’s IoPPN said, “Seeing the once-deaf mice respond to sounds after treatment was truly thrilling. It was a pivotal moment, demonstrating the tangible potential to reverse hearing loss caused by defective genes. This groundbreaking proof-of-concept study unlocks new possibilities for future research, sparking hope for the development of treatments for hearing loss.”
This study was possible thanks to funding from the Medical Research Council, Wellcome, and from Decibel Therapeutics Inc.

The longer a person has type 2 diabetes, the more likely they may be to experience changes in brain structure, a Michigan Medicine study finds.
Researchers analyzing data from 51 middle-aged Pima American Indians living with type 2 diabetes used a series of memory and language tests developed by the National Institutes of Health, called the NIH Toolbox Cognitive Battery, as well as MRI, to determine the relationship between diabetes, cognition and makeup of the brain.
Brain imaging suggested that study participants with longer durations of type 2 diabetes had decreased mean cortical thickness and gray matter volumes, and an increased volume of white matter hyperintensities.
The MRI results, researchers say, indicate the negative effects longstanding diabetes may have on brain health outcomes and emphasize the importance of preventing early onset type 2 diabetes.
Cognition in study participants with type 2 diabetes did not differ compared to those without the condition. Results are published in Annals of Clinical and Translational Neurology.
“This is among the first times that alterations of the brain’s structure have been associated with duration of diabetes,” said first author Evan Reynolds, Ph.D., research fellow and lead statistician for the NeuroNetwork for Emerging Therapies at Michigan Medicine
“Although we did not find reduced cognition through the NIH Toolbox, this might not give the entire picture. The fact that we saw negative changes in the brain itself provides evidence for the need for early screening for cognitive disorders in patients with type 2 diabetes to improve patient care and quality of life.”
Investigators also found that diabetes complications, such as chronic kidney disease and damage to the nerves in the heart and blood vessels, are linked to structural changes to the brain. This falls in line with another of the team’s studies, which found that diabetic complications increased the odds of developing a cognitive disorder by 2.45 times in 40 to 60-year-olds.