Scientists have long been studying the brain with a goal of aiding healthier aging. While much is known about risk factors for accelerated brain aging, less has been uncovered to identify ways to prevent cognitive decline.
There is evidence that nutrition matters, and a novel study published in Nature Publishing Group Aging, from the University of Nebraska-Lincoln’s Center for Brain, Biology and Behavior and the University of Illinois at Urbana-Champaign further signals how specific nutrients may play a pivotal role in the healthy aging of the brain.
The team of scientists, led by Aron Barbey, director of the Center for Brain, Biology and Behavior, with Jisheng Wu, a doctoral student at Nebraska, and Christopher Zwilling, research scientist at UIUC, performed the multimodal study — combining state-of-the-art innovations in neuroscience and nutritional science — and identified a specific nutrient profile in participants who performed better cognitively.
The cross-sectional study enrolled 100 cognitively healthy participants, aged 65-75. These participants completed a questionnaire with demographic information, body measurements and physical activity. Blood plasma was collected following a fasting period to analyze the nutrient biomarkers. Participants also underwent cognitive assessments and MRI scans. The efforts revealed two types of brain aging among the participants — accelerated and slower-than-expected. Those with slower brain aging had a distinct nutrient profile.
The beneficial nutrient blood biomarkers were a combination of fatty acids (vaccenic, gondoic, alpha linolenic, elcosapentaenoic, eicosadienoic and lignoceric acids); antioxidants and carotenoids including cis-lutein, trans-lutein and zeaxanthin; two forms of vitamin E and choline. This profile is correlated with nutrients found in the Mediterranean diet, which research has previously associated with healthy brain aging.
“We investigated specific nutrient biomarkers, such as fatty acid profiles, known in nutritional science to potentially offer health benefits. This aligns with the extensive body of research in the field demonstrating the positive health effects of the Mediterranean Diet, which emphasizes foods rich in these beneficial nutrients,” Barbey, Mildred Francis Thompson Professor of Psychology, said. “The present study identifies particular nutrient biomarker patterns that are promising and have favorable associations with measures of cognitive performance and brain health.”
Barbey noted that previous research on nutrition and brain aging has mostly relied on food frequency questionnaires, which are dependent on participants’ own recall. This study is one of the first and the largest to combine brain imaging, blood biomarkers and validated cognitive assessments.

“The unique aspect of our study lies in its comprehensive approach, integrating data on nutrition, cognitive function, and brain imaging,” Barbey said. “This allows us to build a more robust understanding of the relationship between these factors. We move beyond simply measuring cognitive performance with traditional neuropsychological tests. Instead, we simultaneously examine brain structure, function, and metabolism, demonstrating a direct link between these brain properties and cognitive abilities. Furthermore, we show that these brain properties are directly linked to diet and nutrition, as revealed by the patterns observed in nutrient biomarkers.”
The researchers will continue to explore this nutrient profile as it relates healthy brain aging. Barbey said it’s possible, in the future, that the findings will aid in developing therapies and interventions to promote brain health.
“An important next step involves conducting randomized controlled trials. In these trials, we will isolate specific nutrients with favorable associations with cognitive function and brain health, and administer them in the form of nutraceuticals,” Barbey said. “This will allow us to definitively assess whether increasing the levels of these specific nutrient profiles reliably leads to improvements in cognitive test performance and measures of brain structure, function, and metabolism.”
Barbey is also co-editing an upcoming special collection for the Journal of Nutrition, “Nutrition and the Brain — Exploring Pathways to Optimal Brain Health Through Nutrition,” which is currently inviting submissions for consideration, and articles will begin publishing next year.
“There’s immense scientific and medical interest in understanding the profound impact of nutrition on brain health,” Barbey said. “Recognizing this, the National Institutes of Health recently launched a ten-year strategic plan to significantly accelerate nutrition research. Our work directly aligns with this critical initiative, aiming to contribute valuable insights into how dietary patterns influence brain health and cognitive function.”

Birmingham researchers have shown PEPITEM, a naturally occurring peptide (small protein) holds promise as a new therapeutic for osteoporosis and other disorders that feature bone loss, with distinct advantages over existing drugs.
PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) was first identified in 2015 by University of Birmingham researchers.
The latest research, published today in Cell Reports Medicine, show for the first time that PEPITEM could be used as a novel and early clinical intervention to reverse the impact of age-related musculoskeletal diseases, with data demonstrating that PEPITEM enhances bone mineralisation, formation and strength, and reverses bone loss in animal models of disease.
The research was funded by major grants from the Medical Research Council and the Lorna and Yuti Chernajovsky Biomedical Research Foundation, which funds pioneering research into the creation of new targeted medicines to improve health. Other funders included the British Society for Research on Ageing, and Versus Arthritis.
Bone is constantly formed, reformed, and remodelled throughout life, and up to 10% of human bone is replaced annually through a complex interplay between two cell types — osteoblasts, which form bone, and osteoclasts, which breakdown bone. Disturbances to this tightly orchestrated process are responsible for features of diseases such as osteoporosis and rheumatoid arthritis, which show excessive bone breakdown, or ankylosing spondylitis, where abnormal bone growth occurs.
The most commonly used osteoporosis therapies (bisphosphonates) target osteoclasts to prevent further bone loss. Although there are new ‘anabolic’ agents that can promote new bone formation, these have limitations in their clinical use, with teriparatide (parathyroid hormone, or PTH) only being effective for 24 months and romosozumab (anti-sclerostin antibody) being associated with cardiovascular events.
Therefore, there is a clear case for developing new therapies to stimulate bone repair in age-related musculoskeletal diseases, of which osteoporosis is the most common. Researchers led by Dr Helen McGettrick and Dr Amy Naylor, including Dr Jonathan Lewis and Ms Kathryn Frost, from the Institute of Inflammation and Ageing at the University of Birmingham and Dr James Edwards from Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford set out to investigate the potential therapeutic impact of PEPITEM in these disease states.

PEPITEM is a naturally occurring short protein (peptide) produced in the body and found circulating in everyone at low levels.
The research findings demonstrated that PEPITEM regulates bone remodelling and that increasing the amount present in the body stimulates bone mineralisation in ‘young bones’ that are not in a diseased or pre-osteoporotic state, and that this translates to an increase in bone strength and density similar to current standard of care drugs (bisphosphonates and PTH).
However, the key test for a potential new therapeutic is its ability to target the natural repair process that is compromised by age, or inflammatory disease. Here the researchers showed that giving additional PEPITEM limits bone loss and improves bone density in animal models of the menopause, which is a common trigger for osteoporotic bone loss in humans. Their studies also showed similar findings in models of inflammatory bone disease (arthritis), where PEPITEM significantly reduced bone damage and erosion.
These findings were underscored by studies using human bone tissue, harvested from older patients during joint surgery. These studies showed cells from older individuals respond to PEPITEM, significantly increasing the maturation of osteoblasts, and their ability to produce and mineralise bone tissues.
Their cell and tissue culture work showed PEPITEM has a direct effect on osteoblasts to promote bone formation, by increasing the activity of osteoblasts rather than their number. Further studies identified the NCAM-1 receptor as the specific receptor for PEPITEM on osteoblasts, and strongly suggested the NCAM-1- b-catenin signalling pathway is responsible for the upregulation of osteoblast activity. This receptor, and the pathway, are distinct from PEPITEM receptors that have been previously described in other tissues.
The researchers also investigated PEPITEM’s effect on osteoclasts and bone resorption. Here, mouse studies showed PEPITEM significantly reduces the number of osteoclasts, leading to reduced bone mineral resorption. The researchers subsequently demonstrated that the reduction in osteoclast activity is the result of a soluble substance released locally in bone tissues by osteoblasts ‘activated’ by PEPITEM.
Dr Helen McGettrick said: “While the most commonly used drugs, bisphosphonates, work by blocking the action of osteoclasts, PEPITEM acts by swinging the balance in favour of bone formation, without impacting the ability of osteoclasts to resorb regions of damaged or weak bone tissue via normal bone remodelling.”
Helen Dunster, the Business Development Manager who has curated the intellectual property associated with PEPITEM for the last 8 years says: “PEPITEM is the subject of a number of patent families relating to its activity in inflammation and inflammatory immune-mediated, bone and obesity related diseases, and also comprising of smaller PEPITEM pharmacophores. A US patent application (US18488234) covering the use of PEPITEM in the treatment or prevention of bone disease, has a priority filing date of 8/10/2019.”

Upward social mobility may ward off dementia, according to a new study. Dementia, a collective term for conditions marked by memory loss and diminished cognitive functioning, strains healthcare systems and devastates quality of life for patients and their families. Research thus far has found correlations between socioeconomic status (SES) — Parent’s asset, education level, income, and work status — and susceptibility to dementia, and SES changes throughout a person’s life, known as social mobility, seem to influence this risk; however, scientific evidences are lacking.
The new study, led by Osaka University researchers and published in JAMA Network Open, provides data-backed evidence that upward social mobility is associated with a lower dementia risk. Specifically, a downward SES transition was associated with the highest loss of healthy longevity from age 75 onward in their lifetime. Yet, an upward transition was linked with the longest period of healthy longevity. Interestingly, these result from upward are more favorable than those with stable high SES since childhood.
“Thanks to a large and robust dataset, our findings solidify the association between socioeconomic mobility and dementia risk,” the study’s lead author Ryoto Sakaniwa says. “Our finding that upward social mobility throughout a person’s life correlates with a prolonged period of dementia-free aging means that improving socioeconomic conditions could be a key to dementia prevention and healthier longevity.”
The researchers used data from the Japan Gerontological Evaluation Study, which followed 9,186 participants aged 65 and over from 2010 to 2016. The study employed unsupervised clustering analysis and data-driven classification to analyze changes in participants’ SES throughout their lives. The analysis identified six distinct SES transition patterns. The researchers used a national registry of long-term nursing care services to determine dementia incidence, which enabled a detailed examination of the relationship between these transitions and dementia risk.
The analysis found that upward SES transitions were associated with a notably lower risk of dementia incidence compared with stable SES patterns. Conversely, downward SES transitions had a significantly increased risk.
The study also explored the mediating effects of lifestyle behaviors, comorbidities, and social factors on the association of SES transitions and dementia risk. These factors were found to play significant roles in mediating that risk, particularly physical characteristics and lifestyle behaviors in upward transitions and social factors in downward transitions.
“Future research should delve deeper into the mechanisms by which SES influences cognitive health, including potential interventions for mitigating dementia risk,” senior author Hiroyasu Iso says.” Understanding the nuances of how SES and its transitions impact dementia is vital for developing targeted strategies addressing underlying socioeconomic factors throughout one’s life.

Surgical teams at NYU Langone Health performed the world’s first genetically modified pig kidney transplants into a human body in September and November 2021, and then transplanted two pig hearts in the summer of 2022. These procedures were done in patients declared dead based on neurologic criteria (decedents) and maintained on ventilators with the consent of their families. Demonstrating the field’s progress, NYU Langone in April 2024 transplanted a pig kidney into a living patient.
Now two new analyses, one published online on May 17 in Nature Medicine and the other May 21 in Med, reveal changes at the single-cell level in the organs and recipient’s bodies before, during, and just after the xenotransplantation surgeries in the decedents. Teams of scientists had worked alongside the surgeons, taking blood and tissue samples to analyze changes in tens of thousands of collected cells.
Led by researchers at NYU Grossman School of Medicine and the Broad Institute of MIT and Harvard, the Med paper tracked the genetic and cellular activity in the two pig kidneys transplanted into humans, and compared them against pig kidney samples that had not been translated. To do so, the research team used several techniques, including single-cell RNA sequencing, which determined the order (sequence) of the molecular letters making up the pig and human genes active in various cell types during the procedures.
The study showed that the transplanted pig kidneys, while not rejected outright by the recipients’ bodies (no immediate kidney failure), caused a strong reaction in human peripheral blood mononuclear cells (PBMCs). This set of immune cells can attack transplanted (foreign) organs much like they attack foreign invaders (e.g. viruses). While immediate rejection was not seen, in part due to treatment with medications that suppressed it, the new study found evidence of subtler reactions that could cause xenotransplants to fail over time.
Specifically, the pig kidneys were seen to trigger “antibody-mediated rejection” at the molecular level. As the body develops immune proteins called antibodies specific to a transplanted organ, they recruit natural killer cells, macrophages, and T cells that can injure it. The team also saw an uptick in pig kidneys of tissue repair mechanisms, where certain cells multiply as part of the growth involved in healing. Normal cells that transform into cancer cells also grow aggressively, so the mechanism bears watching.
“We have detailed the cellular mechanisms that dictate how human immune cells react to a xenotransplant in the short term,” said Jef Boeke, PhD, a co-senior author on both studies, and director of the Institute for System Genetics at NYU Grossman School of Medicine. “These results give us new insights into how we might further engineer pig organs for transplant, or tailor immunosuppression treatments to improve tolerance of a foreign organ.”
By tracking the interplay between the kidneys and human system several times each day, the researchers found that pig kidney immune cells drove reactions right after the transplant, but that human immune cells infiltrated the pig organs by 48 hours to dominate signaling. Measuring the degree to which pig immune cells trigger the first wave of immune attack on xenotransplants will shape efforts to prevent irreversible cellular damage to them, say the study authors.

Transplanted Hearts
The other new paper, published in Nature Medicine, featured a “multiomics” analysis of pig hearts and surrounding human cells in decedents. This included analyses every six hours after transplant of gene activity (transcriptomics), as well of proteins (proteomics), lipids, and metabolites (intermediates in biological pathways) present in cells.
Rapid, massive increases in the number of certain cell types were also seen in decedents receiving pig hearts. In one of the decedents (D1) but not the other, activated T cell and natural killer (NK) cell populations within the PBMC group increased from about one percent 30 hours post-transplant to more than 20 percent of the entire PBMC population by 66 hours after the procedure. This dramatic immune reaction to the organ, a complication called perioperative cardiac xenograft dysfunction (PCXD), came with a damaging inrush of immune cells (inflammation), and misplaced healing attempts (tissue remodeling) that thicken tissue and can hinder function.
The worse outcomes experienced by the one decedent may be partly because this heart was smaller than anticipated for the recipient’s size, and required an extra procedure to compensate for it, the researchers said. These factors may have cut off blood flow and the oxygen supply to the heart for longer, which is known to cause ischemia reperfusion injury when the supply is restored. The research team observed that PCXD-related immune reactions to the pig organ got worse in the presence of this recipient’s reperfusion injury.
“This study demonstrated that multiomics can be used to reveal a broad picture of what is happening in the recipient of a xenograft,” said Brendan Keating, PhD, a co-senior author on both studies and faculty in Department of Surgery at NYU Grossman School of Medicine. “The team that did the xenotransplant had several theories about why the first decedent was having more issues, but multiomics helped to define the complications, and may be used to counter them moving forward.”

The human genome consists of around 3 billion base pairs and humans are all 99.6% identical in their genetic makeup. That small 0.4% accounts for any difference between one person and another. Specific combinations of mutations in those base pairs hold important clues about the causes of complex health issues, including heart disease and neurodegenerative diseases like schizophrenia.
Current methods to model or correct mutations in live cells are inefficient, especially when multiplexing — installing multiple point mutations simultaneously across the genome. Researchers from the University of California San Diego have developed new, efficient genome editing tools called multiplexed orthogonal base editors (MOBEs) to install multiple point mutations at once. Their work, led by Assistant Professor of Chemistry and Biochemistry Alexis Komor’s lab, appears in Nature Biotechnology.
Komor’s team was especially interested in comparing genomes that differ at a single letter change in the DNA. Those letters — C (cytosine), T (thymine), G (guanine), A (adenosine) — are known as bases. Where one person has a C base, another person might have a T base. These are single nucleotide variants (SNVs) or single point mutations, a person might have 4-5 million variants. Some variants are harmless; some are harmful; and often it is a combination of variants that confers disease.
One issue with using the genome in disease modeling is the sheer number of possible variations. If scientists were trying to determine which genetic mutations were responsible for heart disease, they could decode the genomes of a cohort that all had heart disease but the number of variations between any two people makes it very hard to determine which combination of variations causes the disease.
“There is a problem interpreting genetic variants. In fact, most variants that are identified are unclassified clinically, so we don’t even know if they’re pathogenic or benign,” stated Quinn T. Cowan, a recent Ph.D. graduate from the university’s Department of Chemistry and Biochemistry and first author on the paper. “Our goal was to make a tool that can be used in disease modeling by installing multiple variants in a controlled laboratory setting where they can be studied further.”
An evolution in gene-editing
To understand why MOBEs were created, we have to understand the limitations of the traditional gene-editing tool CRISPR-Cas9. CRISPR-Cas9 uses a guide RNA, which acts like a GPS signal that goes straight to the genomic location you want to edit. Cas9 is the DNA-binding enzyme that cuts both strands of the DNA, making a complete break.

Although relatively straightforward, double-stranded breaks can be toxic to cells. This kind of gene-editing can also lead to indels — random insertions and deletions — where the cell is not able to perfectly repair itself. Editing multiple genes in CRISPR-Cas9 multiples the risks.
Instead of CRISPR, Komor’s lab uses a base-editing technique she developed, which makes a chemical change to the DNA, although only one type of edit (C to T or A to G, for example) can be made at a time. So rather than scissors that cut out an entire section at once, base-editing erases and replaces one letter at a time. It is slower, but more efficient and less harmful to cells.
Simultaneously applying two or more base editors (changing a C to T at one location, and an A to G at another location in the genome), allows for better modeling of polygenic diseases — those occurring due to more than one genetic variant. However, a technology didn’t exist that could do this efficiently without guide RNA “crosstalk,” which happens when base editors make unwanted changes.
Cowan’s MOBEs use RNA structures called aptamers — small RNA loops that bind to specific proteins — to recruit base-modifying enzymes to specific genomic locations enabling simultaneous editing of multiple sites with high efficiency and a lower incidence of crosstalk.
This system is novel and is the first time someone used aptamers to recruit ABEs (adenosine base editors) in combination with CBEs (cytosine base editors) in an orthogonal pattern to make the MOBEs.
The differences are stark: when CBE and ABE are given together not using MOBE, crosstalk occurs up to 30% of the time. With MOBE, crosstalk is less than 5%, while achieving 30% conversion efficiency of the desired base changes.

The study was a proof of principle to test the feasibility of the MOBE system, which has been granted a provisional patent. To test them even further, the team conducted several case studies with real diseases, including Kallmann syndrome, a rare hormonal disorder. Their experiments revealed that MOBE systems could be used to efficiently edit relevant cell lines of certain polygenic diseases.
“We’re in the process of putting the plasmids up on AddGene so anyone can freely access them. Our hope is that other researchers will use the MOBEs to model genetic diseases, learn how they manifest and then hopefully create effective therapies,” stated Cowan.
This research was funded in part by the National Institutes of Health (1R35GM138317, T32 GM008326, and T32 GM112584) and the Research Corporation for Science Advancement (28385).
Full list of authors: Quinn T. Cowan, Sifeng Gu, Wanjun Gu, Brodie L. Ranzau, Tatum S. Simonson, and Alexis C. Komor (all UC San Diego).

Periodontal disease, represented by periodontitis, is the leading cause of tooth loss and affects close to one in five adults worldwide. In most cases, this condition occurs as a result of an inflammatory response to bacterial infection of the tissue around teeth. As the condition worsens, the gums begin to pull away, exposing teeth roots and bone. Notably, the incidence of periodontitis becomes more prevalent with age and with populations worldwide living longer, developing a solid understanding of its underlying causes and progression is important.
In a study recently published in Nature Communications on March 28, 2024, researchers from Tokyo Medical and Dental University (TMDU) found a way to achieve this by improving upon a widely used animal model to study periodontitis.
Studying periodontitis directly in humans is challenging. As a result, scientists often resort to animal models for preclinical research. For instance, the “mouse ligature-induced periodontitis model,” since its inception in 2012, has enabled researchers to study the cellular mechanisms underlying this condition. Simply put, with this model, periodontal disease is artificially induced by ligating silk threads onto the molars of mice models, which induces plaque accumulation. While convenient and effective, this model, however, fails to capture the complete picture of periodontitis. “Even though the periodontal tissue is composed of gingiva, periodontal ligament, alveolar bone, and cementum, analyses are usually performed exclusively on gingival samples due to technical and quantitative limitations,” remarks lead author Mr. Anhao Liu. “This sampling strategy limits the conclusions that may be drawn from these studies, so methods that allow for the simultaneous analysis of all tissue components are needed.”
To address this limitation, the research team developed a modified ligature-induced periodontitis model. Instead of the classic single ligature, they used a triple ligature approach on the upper left molar of male mice. This strategy expanded the range of bone loss without causing severe bone destruction around the second molar, increasing the yield of the different types of periodontal tissue. “We isolated the three main tissue types and evaluated the RNA yield between the two models. The results showed that the triple-ligature model effectively increased the yield, achieving four times the yield of normal peri-root tissue and supporting the high-resolution analysis of different tissue types,” explains senior author Dr. Mikihito Hayashi.
After confirming the efficacy of their modified model, the researchers proceeded to investigate the effects of periodontitis on gene expression among the different tissue types over time, focusing on genes related to inflammation and osteoclast differentiation. One of their main findings was that the expression of the Il1rl1 gene was markedly higher in peri-root tissue five days after ligation. This gene encodes the protein ST2 in both receptor and decoy isoform, which binds to a cytokine called IL-33 that is involved in inflammatory and immunoregulation processes.
To gain further insights into the role of this gene, the team induced periodontitis in genetically modified mice that lacked the Il1rl1 or Il33 genes. These mice exhibited accelerated inflammatory bone destruction, highlighting the protective role of the IL-33/ST2 pathway. Further analysis of cells containing the ST2 protein in its receptor form, mST2, revealed that most of them were of macrophage lineage. “Macrophages are typically classified into two main types, pro-inflammatory and anti-inflammatory, based on their activation process. We found that mST2-expressing cells were unique in that they expressed some markers of both types of macrophages simultaneously,” comments senior author Dr. Takanori Iwata. “These cells were present in the peri-root tissue before inflammation was triggered, so we named them ‘periodontal tissue-resident macrophages.'”
Together, the findings of this study showcase the power of this modified animal model to study the full scope of periodontitis in greater detail, right down to the biomolecular level. “We suggest the possibility that a novel IL-33/ST2 molecular pathway regulating inflammation and bone destruction in periodontal disease, alongside specific macrophages in peri-root tissue, is deeply involved in periodontal disease. This will hopefully lead to the development of new treatment strategies and prevention methods,” concludes senior author Dr. Tomoki Nakashima.

A novel therapy that reprograms immune cells to promote antitumor activity helped shrink hard-to-treat prostate and bladder cancers in mice, according to research from the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy and Johns Hopkins Drug Discovery.
The study was published online May 3 in the journal Cancer Immunology Research, a journal of the American Association for Cancer Research.
Immunotherapies that help the immune system recognize and fight tumors have revolutionized care for many types of cancer. However, these therapies, which ramp up the production and activation of tumor cell-killing immune cells called T-cells, have not been effective in aggressive forms of prostate and bladder cancers. The field of oncology has been trying to find out why and how to make immunotherapies work better in these cancers, explains the study’s senior author, Jelani Zarif, Ph.D., Robert E. Meyerhoff Endowed Professor and associate professor of oncology at Johns Hopkins. Zarif and his colleagues suspected that immune cells called macrophages were to blame. Under some conditions, macrophages help tumors grow and suppress T-cell activity, hampering the immune response to cancers.
“The focus of our work is to reprogram the immune-suppressive tumor-associated macrophages into anticancer immune cells to enhance therapeutic responses to immunotherapies and other standard-of-care cancer therapies,” Zarif says.
The immune-suppressing macrophages rely on the amino acid glutamine. Zarif and his colleagues previously demonstrated that macrophage precursor cells called monocytes will develop into immune-activating macrophages if they are grown in a laboratory setting without glutamine. By contrast, when monocytes are grown with glutamine, they become immune-suppressing macrophages.
Zarif and his team hypothesized that drugs blocking the immune cells from accessing glutamine would shift the balance of macrophages toward the immune-stimulating type and help shrink tumors. Studies have shown that a drug called 6-diazo-5-oxo-L-norleucine (DON) that starves tumors of glutamine shrinks tumors that depend on glutamine to grow. But development of the drug as a therapy for cancer was abandoned decades ago because it was also toxic to the gastrointestinal system and caused harmful side effects.
Instead, Zarif tapped an experimental glutamine-blocking drug developed by study co-authors Barbara Slusher, Ph.D., director of Johns Hopkins Drug Discovery, and Jonathan Powell, M.D., Ph.D., former associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy. The drug, JHU083, is a type of molecule called a prodrug that cells inside the body convert into an active drug. Specifically, JHU083 can only be turned into its active, glutamine-blocking form inside the tumor, preventing it from causing harmful side effects elsewhere in the body. Studies show the drug shrinks tumors, reduces cancer spread and increases survival in animals with cancers of the skin, colon, blood and brain, as well as certain treatment-resistant breast cancers.

“Barbara Slusher and her team changed the drug’s chemistry so it can circulate inactive throughout the body, and it only becomes active when it gets inside cancer cells,” Zarif explains. “Because the active form is only released to cancer cells, you can give a lower dose, further reducing the risk of side effects.”
Zarif and his colleagues showed that JHU083 blocks the use of glutamine in prostate and bladder tumors in mice, reducing tumor growth and triggering tumor cell death. It also reprogrammed immune-suppressing macrophages into immune-boosting macrophages. The macrophages themselves started destroying tumor cells. They also helped recruit tumor-killing T-cells and natural killer cells to the tumors. Adding an immunotherapy called a checkpoint inhibitor, which boosts the activation of T-cells in tumors, did not increase the effects of JHU083. Zarif explained this is likely because there was already so much antitumor immune activity in the JHU083-treated tumors.
“JHU083 could be a promising anti-cancer therapy for tumors with immune-suppressing macrophages and too few T-cells,” he says. “It might also be a promising agent for tumors that do not respond to checkpoint inhibitors.”
Zarif plans to collaborate with colleagues at Johns Hopkins to launch a clinical trial of JHU083 in patients with treatment-resistant prostate or bladder cancer to see if it shrinks tumors and prevents metastasis. They also want to continue studying whether combining JHU083 with other treatments improves its effectiveness against tumors.
The study’s other co-authors were Monali Praharaj, Fan Shen, Alex J. Lee, Liang Zhao,Thomas R. Nirschl, Debebe Theodros, Alok K. Singh, Xiaoxu Wang, Kenneth M. Adusei, Kara A. Lombardo, Raekwon A. Williams, Laura A. Sena, Elizabeth A. Thompson, Ada Tam, Srinivasan Yegnasubramanian, Edward J. Pearce, Robert D. Leone, Jesse Alt, Rana Rais and Drew M. Pardoll of Johns Hopkins.
This work was supported in part by the Bloomberg∼Kimmel Institute for Cancer Immunotherapy, a Prostate Cancer Foundation Young Investigator Award, the National Institutes of Health/National Cancer Institute (grant K22 CA237623), the National institutes of Health (grants #R01CA283649 and #R01CA229451) and a Maryland Cigarette Restitution Fund grant (#FHB33CRF).
The Johns Hopkins University has filed patent applications related to technologies described in the paper on which Slusher, Powell, Leone, Rais and Alt are listed as inventors. Slusher, Powell and Rais are also co-founders of and consultants for Dracen Pharmaceuticals. These relationships are being managed by Johns Hopkins University in accordance with its conflict-of-interest policies.

Stormont has backed Northern Ireland becoming part of a new Westminster law that would stop young people born since 2009 from ever smoking.

Published19 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Nick TriggleHealth correspondentInfected blood victims could each receive payments of more than £2 million under a compensation scheme announced by the government.Ministers set out the figures as they unveiled the proposed scheme following publication of the public inquiry’s report into the scandal on Monday.That said authorities covered up the scandal and exposed victims to unacceptable risks.The government said the first payments will be made by the end of the year.In the meantime, it said it would make extra interim payments of £210,000 over the summer.Those will be to 4,000 victims who have already received payments of £100,000.But the government said compensation would eventually be made available to a much wider group of people, including to the family and loved-ones of those who have been infected. This could include the children or parents – the first time they will have received any financial payment.The total cost could eventually be in the region of £10 billion.The infected blood inquiry has been called the worst treatment disaster in the history of the NHS.More than 30,000 people were infected with HIV and hepatitis C from 1970 to 1991 by contaminated blood products and transfusions.About 3,000 of them have since died – many haemophiliacs given infected blood products as part of their treatment.’Five criteria’The compensation due will be judged under five criteria:injury and harm causedsocial impact from stigma and isolationimpact on autonomy and private life, such as not being able to have childrencare costsfinancial lossThe government said payments would depend on individual circumstances, but typical payouts for those infected with HIV, or for HIV plus hepatitis, would be in excess of £2 million.Those with a hepatitis infection causing liver damage would get around £1 million.Those who face extreme care costs or who were very high earners before infection could get even more.Infected blood inquiry: Read moreAt a glance: Infected blood inquiry’s key findingsLIVE: Follow all the latest news and updatesRead more about the victims, families and what happenedInfected blood scandal: Who gets compensation?The school where dozens died in NHS blood scandalI lost mum, dad and baby sister to HIV in blood scandalITV to make drama about contaminated blood scandalThe figures released also give examples of compensation awards for the family members of those infected. The partner of someone infected with HIV who is still alive today, for example, should expect to receive around £110,000, while a child could get £55,000.If their loved-one has died and they were financially dependent on them, annual payments are available.The scheme will be administered by a new body called the Infected Blood Compensation Authority, which will be led initially by Sir Robert Francis, who chaired the inquiry into the Stafford Hospital scandal. It is proposed that the compensation will be taken as a lump sum or series of payments. The plans will be consulted on over the coming weeks.From next April, the compensation scheme will effectively replace the existing financial support scheme – versions of which have been in place since 1989. In recent years they have been worth more than £40,000 a year to some, such as those who have been infected or, if they have died while benefitting, their partners.Image source, Getty ImagesAnnouncing the details in the House of Commons, paymaster general John Glen repeated the apology made by Prime Minister Rishi Sunak on Monday, saying the victims had suffered “unimaginable pain”.He said the publication of the public inquiry’s report was a “day of great humility for everyone”.He hopes the compensation package will be welcomed: “The infected blood community know their cries for justice have been heard.”Jason Evans, of the campaign group Factor 8, said he would need to carefully consider the compensation sums before commenting.He is concerned about the wait some face given the interim payments are only available to certain individuals. “Today’s announcement will be a gut-punch to most bereaved families, who have still received no compensation at all.”More on this storyI lost my mum, dad and baby sister to HIV in infected blood scandalPublished13 MayChildren used as ‘guinea pigs’ in clinical trialsPublished18 AprilWhat is the infected blood scandal and will there be compensation?Published18 minutes agoAround the BBCBBC iPlayer: Behind the Stories – Infected Blood InquiryUK infected blood inquiry – BBC NewsRelated Internet LinksInfected Blood Inquiry reportThe BBC is not responsible for the content of external sites.

Published22 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesThe UK Covid Inquiry has opened its investigation into the impact of the pandemic on children and young people.,