Tag Archives: treatment

Antibody treatment restores immune function in elderly mice

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Antibodies are proteins that can target and attack specific cells.

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An experimental treatment rejuvenates the immune systems of older mice and improves the animals’ ability to fight infections. If this treatment is effective in humans, it could reverse the age-related decline in immunity that makes older people more susceptible to illness.

These reductions may be due to changes in blood stem cells, which can develop into all types of blood cells, including important components of the immune system. As we age, a greater proportion of these stem cells tend to produce some immune cells than others. Jason Ross at Stanford University in California. This imbalance impairs the immune system’s ability to fight infection. It also promotes chronic inflammation, which accelerates aging and increases the risk of age-related diseases such as heart disease, cancer, and type 2 diabetes.

Ross and his colleagues have developed a treatment that uses antibodies, proteins that recognize and attack specific cells, to target these biased stem cells. Next, they tested the treatment on six mice aged 18 to 24 months. This is roughly equivalent to a human being between 56 and 70 years old.

One week after receiving the antibody injection, these abnormal stem cells in the mice had decreased by about 38 percent compared to six rodents of the same age who did not receive treatment. They also had significantly higher amounts of two types of white blood cells important for recognizing and fighting pathogens, and lower levels of inflammation.

“You can think of this as turning back the clock,” says Ross. “We are adjusting these percentages [immune] more similar cells [those of] A young adult mouse. ”

To test whether these changes result in a stronger immune system, the researchers vaccinated 17 older mice with a mouse virus. Nine of these mice had received antibody treatment eight weeks earlier. The researchers then infected rodents with the virus. After two weeks, the number of infected cells in the animals was measured and it was found that almost half of the treated mice (4 out of 9) had completely cleared the infection, compared to 1 out of 8 of the untreated mice. It turned out that there was only one.

Taken together, these findings demonstrate that antibody treatment rejuvenates the immune system of aged mice. Humans, like rodents, have more abnormal blood stem cells as they age, so a similar antibody treatment could also boost their immune systems, Ross said.

Such a possibility is still far away, robert signer at the University of California, San Diego. First, we need a better understanding of the potential side effects of treatments. In an accompanying article, Signer and his colleagues write: Yasar al-Fat KassResearchers, also at the University of California, San Diego, suggest that depletion of stem cells, even abnormal stem cells, may increase cancer risk. On the other hand, “if you have a better immune system, you’ll be better at investigating cancer, so we don’t know exactly what will happen yet,” Signer says.

Still, Ross says these findings are a promising advance in understanding age-related immune decline and how to reduce it.

Aging is the biggest risk factor for various diseases. “Rejuvenating or improving immune function in older adults could really help fight infectious diseases,” Signer says. “It may also have an impact on different types of chronic inflammatory diseases. That’s what’s so exciting here.”

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Source: www.newscientist.com

Is gene therapy a viable treatment for hemophilia B?

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Hemophilia B is a blood disorder that affects about 30,000 people in the United States. Individuals with hemophilia B have a deficiency in factor IX, a protein essential for proper blood clotting. This condition is hereditary, leading to the inability to clot blood effectively.. Treatment for hemophilia B involves injecting factor IX into the veins, but this method is costly and time-consuming. Therefore, scientists are exploring alternative treatments for hemophilia B.

A team of British researchers conducted a gene therapy trial using adenovirus FLT180a to increase factor IX levels in the livers of hemophilia B patients. They administered this gene therapy to a total of 10 male patients with severe or moderate hemophilia B, aged between 25 to 67 years. The patients were given different doses of the adenovirus and monitored for 26 weeks.

The results of the trial showed that some patients reached normal factor IX levels, while others experienced dangerously high levels. Patients who received lower doses had factor IX levels ranging from 40% to 60% of normal, while those who received higher doses had levels up to 300% of normal. The researchers noted varying responses in different patients and observed side effects like unexpected bleeding.

Despite the variability in patient response, the researchers believe that gene therapy could be a potential treatment for increasing factor IX levels in hemophilia B patients and improving blood clotting. They caution about the need to monitor and manage side effects effectively and suggest that this therapy could provide benefits for up to a year before requiring further intervention.


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Source: sciworthy.com

A groundbreaking treatment on the horizon for controlling and preventing cancer

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It is estimated that one in two people will develop cancer during their lifetime. However, advancements in diagnosis and treatment have led to more people surviving cancer than ever before. The question now is, will this trend of increasing survival rates continue, and how close are we to finding a cure?

The trend of improving survival rates is likely to continue, but the discovery of a cure for cancer is complicated due to the fact that cancer is not a single disease, but rather a group of over 200 diseases, each with its own unique characteristics. Despite this complexity, all cancers originate from mutant cells that divide uncontrollably.

While cancer cells evade normal controls on cell division, targeted cancer therapy has emerged as a promising treatment approach. This therapy focuses on inhibiting genetic mutations that drive cancer growth and has shown to be more effective with fewer side effects than traditional treatments like chemotherapy and radiation therapy.

Targeted therapies like hormone therapy and drugs such as imatinib have revolutionized the treatment of certain types of cancer, improving survival rates significantly. The development of new drugs and the repurposing of existing ones have been accelerated by genetic technologies that utilize big data to understand genetic changes driving cancer.

The power of big data

Advances in cancer treatment have been further propelled by genetic technologies and clinical trials that utilize big data to develop new drugs and repurpose existing ones. The Cancer Genome Atlas Project, for example, provides valuable genetic information for various types of cancer, allowing for targeted treatments based on individual genetic profiles.

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While drug treatments have seen significant advancements, immunotherapy has also emerged as a promising approach in cancer treatment. Immunotherapy aims to boost the patient’s immune system to detect and destroy cancer cells more effectively. This field is rapidly evolving, with treatments like immune checkpoint inhibitors and adoptive cell therapy showing promising results.

Vax is on track

Developments in cancer immunization, including mRNA-based vaccines, are changing the landscape of cancer treatment by utilizing the body’s immune system to target cancer cells. Early diagnosis remains crucial in cancer treatment, with advancements in AI technology offering improved diagnostic capabilities.

Prevention is also a key focus in the fight against cancer, with vaccines against infectious causes of cancer such as HPV and HBV showing promising results. Additionally, cancer prevention strategies using drugs or vaccines to eliminate cancer cells before they form detectable tumors are gaining traction.

While a single “cure” for cancer may be unlikely, ongoing advancements in diagnosis, treatment, and prevention offer new hope to cancer patients worldwide. The future of cancer treatment holds the promise of personalized medicine, targeted therapies, and innovative approaches to combat this complex disease.

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Source: www.sciencefocus.com

Starting Drug Treatment Early Improves Outcomes for Crohn’s Disease Patients

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Crohn’s disease can cause abdominal pain, diarrhea, and weight loss

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A one-year study of 386 people found that receiving advanced treatment soon after diagnosis of Crohn’s disease improves outcomes for patients.

This disease is a lifelong inflammatory bowel disease; impact millions of peopleIn the world. Symptoms include abdominal pain, diarrhea, fatigue, and weight loss.

“These symptoms have a huge impact on people’s quality of life, education, relationships, and ability to work,” he says. Miles Parks at Cambridge University. “While there is no cure, there are ways to reduce some of these negative outcomes.”

Treatment often includes dietary changes, immunosuppressants, and steroids. In the UK, a drug called infliximab (an antibody that targets a specific protein in the body that is thought to contribute to intestinal inflammation) is given to people who regularly experience flare-ups of Crohn’s disease, or other mild symptoms. It can be prescribed to people who are not responding to. Treatment.

“This is a ‘step-up’ approach where treatment is progressively escalated in a reactive manner as the disease returns,” he says. Nurlaminnuralso at the University of Cambridge.

To see what happens if this more powerful treatment is used as early as possible, Parkes and Noor et al. studied 386 newly diagnosed Crohn’s disease patients aged 16 to 80 in the UK. Recruited people.

They were divided into two groups. One patient received infliximab immediately regardless of symptoms, and the other was treated with other Crohn’s disease drugs. If symptoms persist or continue to worsen, participants in the second group will also be prescribed infliximab, in line with a “step-up” approach.

After one year, 80 percent of patients who initially received infliximab had their symptoms under control over time, compared with only 15 percent of those who did not receive treatment immediately.

Additionally, only 0.5% of people in the group who received infliximab immediately required abdominal surgery for Crohn’s disease, compared to 4.5% in the second group.

The results of this study suggest that giving patients with Crohn’s disease intensive treatment as soon as they are diagnosed may be more effective in improving their lives, Dr. Noor said.

Parks said the extra money spent on medication would be balanced out by not having to pay for subsequent scans, colonoscopies and surgeries for people with repeated relapses.

“People with Crohn’s disease don’t want to be hospitalized or undergo surgery. They want to go out into the outside world and live their lives. Anything that speeds the path to remission. It can only be a good thing,” says Ruth Wakeman of the charity Crohn’s & Colitis UK.

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Source: www.newscientist.com

Ultrasound treatment activates sluggish sperm movement

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Sperm that don't move fast enough have a hard time reaching the egg and can cause fertility problems.

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Laboratory research has revealed that applying ultrasound to immobile sperm causes it to move. If sperm does not move properly, it becomes difficult for them to reach the egg, which is a major cause of infertility. With further research, this technology could help improve the success rate of in vitro fertilization (IVF).

Previous research suggests that: High frequency ultrasound increases sperm motility. However, the study did not involve isolating the sperm to assess which individual cells would be beneficial, allowing doctors to find the best cells to use in fertility treatments.

In the latest research, Ali Vafaie The researchers, from Monash University in Melbourne, Australia, classified 50 semen samples into three groups (fast, slow, and stationary) according to sperm motility, based on guidelines for assessing swimming speed.

After separating individual sperm cells from semen samples, the researchers measured the motility of the cells before and after exposure to ultrasound waves with a power of 800 megawatts and a frequency of 40 megahertz.

After 20 seconds of ultrasound, 59 percent of the immobile sperm slowed down, and some started swimming rapidly. Changes in sperm motility peaked at an increase of 266%.

Overall, immotile sperm made up 36% of the samples at the start of the study, but this decreased to just 10% after treatment. It is unclear how long the increase in migration lasted.

Researchers believe that exposure to ultrasound improves dysfunction in sperm's mitochondria, the cells' powerhouses, contributing to increased motility.

This approach could increase the success rate of in vitro fertilization, which requires motile sperm for conception, and could avoid the need for multiple costly surgeries.

But first, Vafai says, the research group will need to test the effectiveness of the approach on sperm, particularly in people experiencing infertility due to reduced sperm mobility. Scientists also need to assess whether it is safe to create embryos from sperm exposed to ultrasound, he says.

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Source: www.newscientist.com

Neuroscientist Luana Colloca aims to revolutionize pain treatment through the power of the placebo effect

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Clove Jetsy; Fierce: Matthew Paul D'Agostino

Despite being a phenomenon known for hundreds of years, there is still much to learn about the placebo effect, which improves health after receiving dummy treatments like sugar pills. It is thought that behind this is the expectation of a positive outcome, and that negative expectations are responsible for the opposite undesirable phenomenon, the nocebo effect, which worsens symptoms. But questions remain about how the mind influences the body in this way and why some people feel its influence more strongly than others.

Luana Colloca are among those grappling with such questions. Colloka, a neuroscientist and director of the Placebo Beyond Opinion Center at the University of Maryland School of Nursing in Baltimore, and colleagues have shown how certain genetic variations shape the extent to which a person responds to a placebo. Ta. They are now studying how best to harness such effects to relieve pain, which could reduce the use of prescription opioid drugs and the risk of addiction to them. They are also exploring the use of virtual reality, with results published last year showing that virtual reality can effectively reduce levels of perceived pain and anxiety.

Colloca shares all of the latest discoveries about the placebo and nocebo effects in her book, which she co-edited. Placebo effect from a translational research perspective.she spoke new scientist About her research on pain relief, whether the placebo effect can help treat mental health conditions, and how it affects our lives…

Source: www.newscientist.com

New Hope for Diabetes Treatment: Repurposed Medicines Present Promising Results

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A recent study led by Indiana University and the University of Chicago Medicine suggests that a drug called alpha-difluoromethylornithine (DFMO) could revolutionize the treatment of type 1 diabetes. Based on a decade of research, DFMO has demonstrated the potential to reduce insulin dependence, and larger clinical trials are currently underway to evaluate DFMO’s impact on beta cell preservation and disease amelioration. Tested.

A recent study led by Indiana University School of Medicine in collaboration with the University of Chicago School of Medicine shows exciting future possibilities for the management of type 1 diabetes and its potential reduction. insulin dependence. The researchers’ findings are cell report medicine, They suggest that repurposing the drug alpha-difluoromethylornithine (DFMO) could open the door to innovative treatments in the future.

Type 1 diabetes is a chronic disease in which the body’s immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood sugar levels and currently requires lifelong insulin treatment to keep patients alive. Is required. Many people living with type 1 diabetes find current treatments, such as daily insulin injections and frequent blood sugar monitoring, inconvenient and difficult to manage.

A 10-year research journey

These latest translation results represent more than a decade of research. Raghu Mirmila, M.D., Ph.D., co-corresponding author of the study, said in 2010 that while running his lab at IU School of Medicine, his team was able to develop beta It was discovered for the first time that cells can be protected from infection. Environmental factors suggest that type 1 diabetes may be preserved. The team then validated these findings in mice.

From 2015 to 2019, Linda DiMeglio, MD, MPH, Edwin Letzter Professor of Pediatrics at IU School of Medicine, Pediatric Endocrinologist and Division Director at Riley Children’s Health, provided guidance to people with newly diagnosed type 1 diabetes. He led a clinical trial to confirm the safety of DFMO. They also suggested that it may stabilize insulin levels by protecting beta cells. The trial was funded by the Juvenile Diabetes Research Foundation (JDRF) and used the drug provided by Panvera Therapeutics.

Dr. Emily K. Sims. Credit: Chapital Photography, provided by Emily K. Sims

“After several years of bench-to-bedside research, Drs. [Sarah] “We are pleased to finally share the promising results from the Tercy mouse model, a pilot study in humans,” said DiMeglio, senior author of the study. “Having established the preliminary safety of DFMO in patients with type 1 diabetes, we are excited to collaborate to further explore its potential benefits in a larger clinical trial.”

Regulatory benefits of DFMO and new formulations

Since 1990, DFMO has been approved by the FDA as a high-dose injectable to treat African sleeping sickness, and in 2020 received breakthrough therapy designation as a post-remission neuroblastoma maintenance therapy. Ta. This prior regulatory approval could streamline adoption as a treatment for type 1 diabetes and shorten the approval process from decades to just a few years.

“Using the new formulation of DFMO as a pill allows patients to take it by mouth rather than needing regular injections, and it has a very favorable side effect profile,” said Dr. said one Milmira. Chicago Medicine. “We are very happy to be able to say that we have developed a drug that works differently than other treatments for this disease.”

Current and future clinical research

Researchers have already begun the next steps to investigate the potential of DFMO. The study’s lead author and co-corresponding author, Emily K. Sims, M.D., associate professor of pediatrics at IU School of Medicine and pediatric endocrinologist at Riley Children’s Health, recently studied the effects of infectious diseases in more detail. To define it, we have begun a large-scale clinical study involving six institutions. His DFMO treatment to preserve beta cell function in type 1 diabetes. This new research was also funded by JDRF and supported by Panbela Therapeutics.

Sims, who is also a physician and scientist at the IU School of Medicine’s Herman B. Wells Pediatric Research Center and Center for Diabetes and Metabolic Diseases, hopes that DFMO, perhaps as part of a combination therapy, will not only help patients; There is. People who have recently been diagnosed with type 1 diabetes but are at risk of developing the condition may also be tested.

“As we embark on this new multicenter clinical trial to further investigate the efficacy of DFMO, we are confident that the encouraging results obtained to date will allow us to modify the underlying disease process of type 1 diabetes. ”Sims said. “We invite even more participants to this pioneering study. With their help, the knowledge we gain today has the potential to shape a brighter future for people affected by type 1 diabetes. Masu.”

Reference: “Inhibition of polyamine biosynthesis preserves beta cell function in type 1 diabetes” Emily K. Sims, Abhishek Kulkarni, Audrey Hull, Stephanie E. Werner, Suzanne Cabrera, Lucy D. Mastrandrea, Batur Hammoud, Soumyadeep Sarkar, Ernesto S. Nakayas, Teresa L. Mastracci, Susan M. Perkins, Ouyang Fangqian, Bobbie Jo Webb Robertson, Jacob R. Enriquez, Sarah A. Turcy, Carmela Evans. · Molina, S. Alice Long, Lori Blanchfield, Eugene W. Garner, Raghavendra G. Mirmila and Linda A. Dimeglio, November 1, 2023; cell report medicine.
DOI: 10.1016/j.xcrm.2023.101261

People who want to know more about New clinical trials can be accessed on the research website.

Source: scitechdaily.com

Revolutionary New Test Promises Breakthrough in Acute Myeloid Leukemia Treatment

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A breakthrough assay to detect acute myeloid leukemia (AML) through a KMT2A gene fusion promises to enhance diagnosis and treatment and represents a major advance in leukemia research.


The researchers Accuracy
Detecting specific molecular markers within leukemia cells has the potential to significantly improve the assessment of measurable residual disease. This advancement will enable better-informed treatment decisions and ultimately improve patient outcomes.

A new assay that detects unique molecular markers in patients with acute myeloid leukemia (AML) could revolutionize how the disease is detected and treated, according to a recently published new report. Molecular Diagnostic Journal Published by Elsevier. This assay may improve the detection of AML due to factors such as: Kuomintang 2A Gene fusions can impact treatment decision-making, assessment of response to treatment, and long-term monitoring.

AML is a rare, aggressive blood cancer that is diagnosed in approximately 120,000 people worldwide each year. Detecting residual disease during treatment is essential to determine prognosis and guide treatment decisions.Currently, methods to detect measurable residual disease (MRD) during treatment of AML include bone marrow morphology, multiparameter flow cytometry (MPFC), and DNA Sequencing.

Morphological evaluation detects leukemic cells only with a detection limit of 5%. Although MPFC has a more sensitive detection limit of 0.01% to 0.001%, it is difficult to implement and interpret and is not standardized across laboratories. DNA sequencing approaches can identify leukemic cells by somatic mutation profiles, but are expensive and can be confounded by clonal hematopoiesis in nonleukemic blood cells.

Breakthrough progress in leukemia research

“We’ve seen a lot of research in this field,” explained lead researcher Dr. Grant A. Challen, of the Department of Oncology at Washington University School of Medicine in St. Louis. Normally absent in healthy cells. Other diseases such as chronic myeloid leukemia (CML) can already be tracked by standard BCR-ABL fusions, and sensitive detection of these fusions has revolutionized the way CML is treated. . For AML patients whose disease is caused by oncogenic fusions, the KMT2A fusion is a molecular marker that can be exploited for sensitive MRD detection. Therefore, we wanted to develop a platform for sensitive KMT2A fusion detection to improve detection and treatment methods for this disease. ”

Researchers have developed a new droplet digital PCR assay that allows for high sensitivity. Kuomintang 2A Fusion detection with the five most common fusion partners.At least 80 are known Kuomintang 2A There are fusion partners, but approximately 80% of fusions involve only 5 partners – AF9, AF6, AF4, Elleand English. They benchmarked the assay in human cell lines and patient samples and demonstrated sensitivity and specificity. Kuomintang 2A Fusion detection.

This assay detects these fusions by splitting cDNA molecules into microfluidic droplets and assaying them using primers and probes that generate a positive signal only when the fused transcript is present. Researchers were able to combine multiple primer/probe sets targeting different fusions into a pooled fusion detection reagent. they again, Kuomintang 2A Fusions in patient samples are known to be present Kuomintang 2A fusion.

Implications for AML treatment and future research

Dr. Challen said: This assay can be easily extended to include additional oncogenic fusions. This has potential implications for treatment decision-making and assessment of response to treatment. Knowing whether treatment is effective is critical to deciding when to escalate treatment or perform a hematopoietic stem cell transplant. ”

“This is a powerful new tool for highly sensitive KMT2A fusion detection and can be directly applied to disease detection in leukemia patients caused by these fusions. This fills a void in oncogenic fusion detection. , we offer several technical improvements. This assay is also highly scalable, and additional fusions can be easily added to the assay to expand coverage of other oncogenic fusions. We is improving blood cancer detection one drop at a time.”

Reference: “Droplet Digital PCR for Oncogenic KMT2A Fusion Detection” by Andrew L. Young, Hannah C. Davis, and Grant A. Challen, October 7, 2023. Molecular Diagnostic Journal.
DOI: 10.1016/j.jmoldx.2023.09.006

This research was funded by: National Institutes of Health and the Leukemia and Lymphoma Society.

Source: scitechdaily.com

Revolutionary Drug Delivery System Transforms Diabetes Treatment

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Stanford University engineers have created an injectable hydrogel depot technology that allows GLP-1 drugs to be administered once every four months, rather than requiring daily injections. This new hydrogel has the potential to revolutionize treatment for type 2 diabetes and weight management by significantly reducing the burden of daily injections.

The hydrogel drug delivery system was developed by materials engineers at Stanford University and turns daily or weekly injections of drugs like Ozempic, Maunjaro, Trulicity, and Victoza into a single injection every four months. This new system could greatly improve patient compliance and health outcomes for people with type 2 diabetes, as well as providing a more manageable treatment regimen.

The hydrogel contains GLP-1 drug molecules and slowly releases them over time, eliminating the need for frequent injections. This novel nanocomposite hydrogel is made of polymers and nanoparticles that dissolve over the course of several months, similar to how a sugar cube dissolves in water. Once the hydrogel is injected under the skin, it gradually releases the drug as it dissolves, providing sustained delivery over a four-month period.

Initial testing in laboratory rats has shown promising results, and future trials will be conducted on pigs to further validate the system’s effectiveness. The ultimate goal is to conduct human clinical trials within the next two years to evaluate the long-term administration of GLP-1-based treatments.

This research was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and a seed grant from the Stanford Diabetes Research Center.

Source: scitechdaily.com

The impact of programmable bacteria on cancer treatment

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Researchers are developing synthetic programmable bacteria to help kill cancerous tissue.Credit: Texas A&M Engineering

https://www.eurekalert.org/news-releases/1009258

https://chat.openai.com/c/6cfb1180-0a40-409b-b230-817e653d2c44

Texas A&M University researchers are co-leading a $20 million project to develop a $1 cancer treatment.

What if a single dose of $1 could cure cancer?

A multi-university research team is receiving federal funding to develop a highly efficient bacterial therapy that targets cancer more precisely and makes treatment safer at a cost of $1 per dose.

Traditionally, cancer treatments have had limited effectiveness in treating patients. Some treatments, such as radiation therapy and chemotherapy, can cause harmful side effects, while others tend to have poor patient response, not to mention the high cost of treatment.Survey results from American Cancer Society Cancer Action Network reports that 73% of cancer survivors and patients are concerned about how they will pay for their cancer treatment, and 51% say they have medical debt from their treatment. For example, cutting-edge cancer treatment can cost up to $1,000,000.

Texas A&M University and the University of Missouri are leading efforts to develop low-cost, safe and controlled cancer treatments. Researchers received a $20 million grant from the Advanced Research Projects Agency for Health (ARPA-H) to fight cancer. The four-year project is part of the current administration’s cancer moonshot plan to boost cancer research and increase funding. It is funded by a newly established agency that aims to accelerate improved health outcomes for all by supporting the development of highly effective solutions to society’s most challenging health problems. It was one of my first projects.

Rapid analysis of cells

$12 million of the grant will go to the Texas A&M Engineering Experiment Station/Texas A&M. Alam Han, Jim Song, and Chelsea Hu are developing programmable synthetic bacteria for immune-induced killing in the tumor environment (SPIKE). The idea is to engineer the bacteria so that the T cells kill the cancerous tissue, and once the cancer is gone, they destroy themselves and are safely excreted out of the body as human waste.

“SPIKE can specifically target tumor cells,” said Han, a professor in Texas Instruments’ Department of Electrical and Computer Engineering. “And because we only target the cancerous tissue and not the surrounding healthy cells, patient safety is dramatically increased. I’m excited to be part of this team tackling a critical health issue that affects so many people. I am very honored.”

Han’s lab is developing high-throughput microfluidic systems that can rapidly process and screen large bacterial therapeutic libraries one cell at a time to rapidly identify the most promising treatments. By fusing microfabrication techniques and biotechnology, these systems create picoliter-scale liquid handling systems that can accurately analyze single cells with high precision and speed, and devices that rapidly analyze individual cells. Realize.

“The big challenge is figuring out how to actually develop these sophisticated microdevices that can run millions of fully automated tests with very little manual or human intervention,” Han said. said. “That’s the engineering challenge.”

Rescue anti-tumor immune cells

While Han innovates and designs microdevices, Song, an immunologist with a background in microbial pathogenesis, T-cell biology, and T-cell-based immunotherapy, has spent the past five years working in bacterial immunotherapy. We are working on this.certain bacteria known as Brucella melitensis At least four types of cancer can be treated by manipulating the human body’s microenvironment and promoting T cell-mediated antitumor immunity.

“We are working on improving Brucella melitensis We can more effectively prevent or suppress tumor growth,” said Song, a professor at Texas A&M School of Medicine. “Our current approach involves finding ways to manipulate bacteria to rescue anti-tumor immune cells and make them more effective at killing tumor cells.

“According to the data so far, BrucellaThe efficiency is dramatically higher than other cancer treatments such as chimeric antigen receptor T-cell therapy and T-cell receptor therapy, with a response rate of over 70%,” said Song.

Safe and controllable treatment

While Professor Song continues to test the effectiveness of bacteria using cancer models, Professor Hu, an assistant professor in Artie McFerrin’s Department of Chemical Engineering and a synthetic biologist, has demonstrated that live bacterial treatments are safe and controllable. We are working to confirm.

” Brucella The strain we are using is attenuated and has been shown to be safe for the host as it lacks key genes required for bacterial virulence,” Hu said. Told. “Ultimately, we want to control the rate at which bacteria multiply within the tumor environment and their ability to self-destruct when their mission is completed.”

To control the rate of growth, the bacteria’s genes are modified to regulate its population, which fluctuates around a certain set point. Hu also plans to incorporate biosensors into the bacteria, allowing them to distinguish between healthy and tumor tissue, allowing them to grow only within the tumor microenvironment.

The bacteria are engineered with receptors that allow patients to take antibiotics after the cancer has gone away. This sends a signal to the bacteria to essentially shred itself and safely remove it from the patient’s body.

“We humans are actually covered in bacteria, and many diseases are caused by imbalances in these bacterial communities,” Hu said. “For example, some people have incredibly fragile stomachs, while others have strong stomachs. The science behind this is that people with strong immune and digestive systems have a healthy gut. It means that it has a population of bacterial cells. There are many possibilities for biological therapy.”

“It’s a really great opportunity to have a great team with the expertise and the ability to push this technology to the forefront,” Hu said. “So the goal is to go into the clinic and provide patients with effective cancer treatment for less than $1 per treatment.”

Tackling difficult problems with unconventional approaches

Other collaborators include Dr. Zhilei Chen of Texas A&M Health Science Center, Dr. Xiaoning Qian of the Department of Electrical and Computer Engineering, and Principal Investigator Dr. Paul de Figueiredo of the University of Missouri.

“The three important advantages of this study are high safety, low cost, and specific targeting of cancerous tumors,” Han said. “We are very excited to be one of the first teams to receive support from ARPA-H, a brand new agency supported by Congress. We take an unconventional approach to tackling difficult problems. High risk, high impact is the hallmark of our approach.”

And the future applications of bacterial engineering that this research unlocks are limitless.

“For our next big project, we will work together to develop bacteria that fight autoimmune diseases such as type 1 diabetes and rheumatoid arthritis,” Song said. Bacteria-based immunotherapy is an exciting frontier in medicine and offers the potential to revolutionize the treatment of autoimmune diseases. With the power of beneficial microorganisms harnessed to modulate the immune system, we are changing the future of medicine. Our research and expertise promises to transform the lives of millions of people, giving them new hope and a healthier tomorrow. ”

Source: scitechdaily.com

Potential New Treatment for Pulmonary Hypertension Discovered by Scientists

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Researchers from Indiana University and the University of Notre Dame focused on reversing vascular remodeling through an epigenetic pathway involving the protein SPHK2, as reported in the journal Circulation Research. A potential treatment has been discovered. This innovative approach could transform the treatment of this serious lung disease.

Researchers at Indiana University School of Medicine’s South Bend Regional Campus and colleagues at the University of Notre Dame have discovered a new therapeutic target to treat pulmonary hypertension. This form of hypertension particularly affects blood vessels in the lungs. The team’s research and findings were recently published in the journal circulation research.

Pulmonary hypertension is a complex and often fatal condition in which the heart works harder than normal to pump blood to the lungs. The exact cause of pulmonary hypertension is unknown, but one of its hallmarks is thickening of pulmonary blood vessels caused by cell overgrowth, also known as vascular remodeling.

Discovery of new treatments

Margaret A. Schwartz, M.D., professor of pediatrics at IU School of Medicine and senior author of the study, said there are few treatments for pulmonary hypertension, and they usually treat the symptoms of vascular remodeling rather than the remodeling itself. Ta.

Dr. Schwartz said that an interesting finding of her team was the discovery of an epigenetic pathway through the protein SPHK2 that can reduce and potentially reverse vascular remodeling in pulmonary hypertension.

Dr. Dushani Ranasinghe (left) and Margaret Schwartz, MD, attend the University of Notre Dame Ranasinghe graduation ceremony.Credit: Provided by Margaret Schwartz

“This is one of the first reversible mechanisms of pulmonary hypertension identified,” she says. “Patients with pulmonary hypertension are usually given drugs to lower blood vessel pressure in the lungs or to help the heart contract to pump blood, both of which are symptoms of vascular remodeling. Our research focuses on targeting an epigenetic reversal of this mechanism. Ultimately, stopping the vascular remodeling process entirely may be the answer.”

Schwartz said the concept is similar to cancer treatment.

“In the case of cancer, we don’t just treat the symptoms, we stop the tumor from growing,” she says. “Vascular remodeling is a different mechanism, but the idea is that treatments target the mechanism rather than the symptoms.”

Main findings and future directions

Other key findings from the study include:

  • SPHK2 promotes the development of pulmonary hypertension through hyperacetylation of histone H3K9 and contributes to vascular remodeling in pulmonary artery smooth muscle cells (PASMCs).
  • SPHK2 deficiency results in decreased pulmonary vascular resistance, right ventricular hypertension, and thickened distal vessel walls.
  • EMAP (endothelial monocyte activation polypeptide) II plays an important role in stimulating the nuclear SPHK2/S1P epigenetic regulatory axis, suggesting cooperation between SPHK2 and S1P.
  • EMAPII may be a major driving force of epigenetic-mediated vascular PASMC reprogramming and remodeling in pulmonary hypertension.
  • Pulmonary endothelial cells are priming factors for the EMAPII/SPHK2/S1P axis that alters PASMC-specific acetylome through histone H3K9 hyperacetylation.

Schwartz and the study’s lead author, Dr. Dushani Ranasinghe, who was a member of Schwartz’s lab when Schwartz was a graduate student at Notre Dame, also thanked Dr. Schwartz for this episode. were interviewed about their findings. Podcast “Discover CircRes”It is produced by. circulation research.

Dr. Schwartz said the next steps in her research include collaborating with Brian Bragg, director of the Warren Center for Drug Discovery and Development at the University of Notre Dame, to further explore the SPHK2 protein as a therapeutic target for pulmonary hypertension. Stated.

Reference: “Changes in smooth muscle cell histone acetylome through the SPHK2/S1P axis promote pulmonary hypertension” A. Dushani CU Ranasinghe, Maggie Holohan, Kalyn M. Borger, Deborah L. Donahue, Rafael D. Kuc, Martin Gerig, Andrew Kim, Victoria A. Propris, Frances J. Castelino, Margaret A. Schwartz, September 12, 2023. circulation research.
DOI: 10.1161/CIRCRESAHA.123.322740

Other IU authors on the study include Maggie Holohan and Martin Gerrig.

This research was made possible in part through funding from the following institutions: National Institutes of HealthLilly Endowment, O’Brien Family Excellence Fund, National Science Foundation, Buckner Family Scholarship.

Source: scitechdaily.com

Next Phase of Human Clinical Trials for Revolutionary Sepsis Treatment Commences

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Scientists have developed a promising treatment for sepsis, and clinical trials using sodium ascorbate, a vitamin C preparation, have shown effective results. The treatment has progressed into extensive clinical trials across Australia and demonstrated significant improvements in sepsis patients, including improved kidney function and reduced dependence on other drugs. This breakthrough, the result of decades of research, brings hope to a disease that is the leading cause of death in intensive care units around the world.

Flory Institute researchers, in collaboration with hospital intensivists, have demonstrated that sodium ascorbate, a pH-balanced formulation of vitamin C, is effective in treating sepsis.

Researchers at the Florey Institute have demonstrated that the formulation they have developed reduces deadly sepsis, and the next phase of clinical trials is set to begin across Australia next month.

Promising results from early clinical trial conducted at Melbourne’s Austin Hospital published in journal Critical carehave shown that sodium ascorbate, a pH-balanced formulation of vitamin C, is effective in treating sepsis.

Lead researcher Associate Professor Yugish Lankadeva said sepsis is notoriously difficult to treat and is often fatal.

LR Florey Professor Clive May, Austin Health Intensivist Professor Rinaldo Bellomo and Florey Associate Professor Yugish Rankadeva discovered that sodium ascorbate can be used to treat sepsis.Credit: Flory

Challenges in sepsis treatment

“Sepsis accounts for 35 to 50 percent of all hospital deaths. It is when the immune system is unable to fight the underlying infection, causing a life-threatening drop in blood pressure, multiple organ failure, and death. ,” said Associate Professor Lankadeva. In our clinical trial at Austin Hospital, sodium ascorbate was administered into patients’ bloodstreams, resulting in promising improvements in multiple organs. ”

Associate Professor Lankadeva, Florey’s research director for Systems Neuroscience, said of the next steps: $4.9 million government-funded research project Delivered in intensive care units in Adelaide, Melbourne, Perth, Brisbane, Alice Springs and Sydney.

“We will recruit 300 adult sepsis patients who will receive either our formulation or a placebo in addition to their usual hospital care. These results will provide additional data to determine the efficacy of the formulation. It will help in collection,” said Associate Professor Lankadeva.

Flory scientists have created a special formulation of sodium ascorbate to treat sepsis.Credit: Flory

Insights into previous trials

Professor Rinaldo Bellomo, director of intensive care research at Austin Hospital, said the first part of the trial at his department involved 30 adult sepsis patients between October 2020 and November 2022.

While in intensive care in the hospital, half of the patients were randomly assigned to receive sodium ascorbate, and the other half received a placebo.

This study found that patients with sepsis treated with sodium ascorbate:

  • Signs that more urine is produced and kidney function has improved
  • Less need for noradrenaline, a drug used clinically to restore blood pressure
  • He showed signs of improved function in multiple organs.

“Sepsis is the number one cause of death in intensive care units in Australia and around the world,” Professor Bellomo said. “In many cases, the disease progresses so rapidly that by the time patients reach us, they are already seriously ill. It will be a huge change.”

Decades of research bear fruit

Professor Clive May, Florey Senior Research Fellow on the project, has been researching how sepsis causes organ failure, particularly damage to the brain and kidneys, for more than 20 years.

“By showing decreased oxygen levels in the tissues of sepsis, we found that sodium ascorbate was a possible treatment.

“We have seen dramatic results in preclinical studies, where extremely high doses of sodium ascorbate caused complete recovery within just three hours with no side effects. It’s heartening to see that it’s paying off and bringing treatments into the hands of patients,” said Professor Clive May.

Surviving sepsis: The patient’s perspective

Longtime Flory staffer Brett Purcell serves as the consumer representative for the MEGASCORES research program, providing a valuable perspective from sepsis survivors.

“In 2011 I was taken to the hospital by ambulance with high fever and delirium. I was suffering from the early stages of sepsis. My condition gradually worsened and I was transferred to a larger hospital after 12 days. By that time My heart was severely infected and I was in septic shock. Six months ago I had a successful aortic valve replacement. Unfortunately the valve was infected.

“The surgical team repaired the damage in a six-hour operation, but my condition deteriorated to critical condition. I was told it would be an hour. It was the good decision-making of the surgical team and ICU intensivist that saved me. I was put on life support with an ECMO machine and dialysis, and my symptoms rapidly worsened. Improved.

“After almost eight weeks in the hospital, I’m home. I’m really lucky to be alive and hope this new research using sodium ascorbate is less invasive, faster, and extremely effective in fighting sepsis.” We hope to provide hospitals with a new and effective life-saving tool.”

Reference: “Ultra-dose sodium ascorbate: pilot, single-dose, physiological effects, double-blind, randomized, controlled trial” Fumitaka Yanase, Sofia Spano, Akinori Maeda, Anis Chaba, Thummaporn Naorungroj, Connie Pei Chen Ow , Yugeesh R. Rankadeva, Clive N. May, Ashenafi H. Betley, Darius JR Lane, Glenn M. Eastwood, Mark P. Plummer, Rinaldo Bellomo, October 12, 2023. Critical care.
DOI: 10.1186/s13054-023-04644-x

Source: scitechdaily.com

Breakthrough in New Coronavirus Treatment: Discovery of New Antiviral Drug

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The Coronavirus Moonshot Consortium report focuses on the discovery of a new class of inhibitors against the main protease of SARS-CoV-2. This global collaboration has generated promising lead compounds, openly shared thousands of compound designs, and represents significant progress in coronavirus drug development.

The COVID Moonshot breakthrough study introduced new non-peptide inhibitors. SARS-CoV-2showcases global collaboration and open science in advancing coronavirus treatments. Although the group’s results have been freely available since its founding in March 2020, the Coronavirus Moonshot Consortium has finally officially reported its results.

Coronavirus Moonshot – An open science, crowdsourced, patent-free drug discovery campaign targeting SARS-CoV-2 virus – A wealth of data has been obtained about the virus’s major proteases, including insights that may pave the way for the development of new and better treatments. “The main treatments described by [these researchers] “Given drug approval timelines and challenges, we may not be ready in time to make an impact on the current pandemic,” write Brian Shoichet and Charles Craik in a related perspective. “Yet, the compounds and the techniques used to identify them may have implications for human health in the future.”

Global cooperation and drug discovery efforts This novel collaboration involved more than 200 volunteer scientists from 47 academic and industrial organizations across 25 countries. “The coronavirus moonshot provides an example of open science drug discovery that could lead to advances in infectious disease drug discovery. This research area is of great public importance but chronically underfunded from the private sector. “There is a shortage,” Melissa et al. write. SARS-CoVB-2 main protease (Mpro) is an attractive target for antiviral drug development due to its important role in viral replication. Current SARS-CoV-2 Mpro inhibitors, such as those drawn from existing antiviral pipelines such as Paxlovid and Xocova, have shown clinical success. However, the use of these compounds remains relatively limited, and their peptidomimetics and covalent scaffolds pose problems for synthesis and administration.

Impact on innovative drug design and open science Hey, Bobby other. describe the discovery of a novel noncovalent and nonpeptidic inhibitor scaffold that is chemically distinct from current Mpro inhibitors. By leveraging a crowdsourcing approach combined with the expertise of hundreds of individuals around the world, Bobby other. We will explain the open science drug discovery campaign. machine learningutilize molecular simulations, and high-throughput structural biology and chemistry to assemble a detailed structural map of the major proteases of SARS-CoV-2 and their biochemical activities.

From over 18,000 compound designs generated by the COVID Moonshot Consortium, the authors identified several non-covalent, non-peptidomimetic compounds, including lead compounds with promising bioavailability, safety, and antiviral activity. identified sex inhibitors. All compound designs from the project are openly shared, building a rich, open, intellectual property-free knowledge base for future anti-coronavirus drug discovery.

Reference:
DOI: 10.1126/science.abo7201

Source: scitechdaily.com

Rare genetic mutations may enhance treatment efficacy for migraine headaches

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Migraines can cause debilitation

Nikki Lloyd/Getty Images

An analysis of the genomes of 1.3 million people has revealed dozens of variations associated with migraine, which could lead to more effective treatments for migraines.

Up to 20% of adults worldwide are thought to experience migraines. Migraines are recurring headaches that are often difficult to treat and can interfere with daily life. Some people have sensory symptoms, such as flashing lights or tingling in the body, before the headache begins, but others do not. It is not known why these two types of migraine, known as migraine with aura and migraine without aura, exist.

“While it is well known that migraines run in families, it has not been easy to identify a clear genetic basis for each subtype,” he says. Debbie Hay at the University of Otago in New Zealand.

now, Kari Stephenson Researchers from the Icelandic biopharmaceutical company deCODE Genetics have identified a genetic variation that appears to influence whether people develop migraines.

Researchers analyzed the DNA of 1.3 million people in Iceland, Denmark, the UK, the US and Norway, and found that around 80,000 of them had experienced migraines.

They discovered 44 genetic mutations associated with the condition, 12 of which had never been reported before. Among these, the research team PRRT2 Genes that help control signaling between neurons are correlated with a greater risk of migraine with aura and epilepsy.

the other A rare mutant that suppresses the function of a gene SCN11A and KCNK5which play a role in transporting sodium and potassium between cells, respectively, and appear to prevent both types of migraines.

The discovery could lead to new treatments that target the causes of migraines, such as drugs that can inhibit the production of a protein encoded by migraines. SCN11A and KCNK5 gene.

“Findings like this should bring great hope to people who suffer from migraine,” Stefansson said. “Current treatments cannot completely eliminate the tendency to develop migraines, so there is a lot of room for better treatments.”

“While great advances have been made in migraine treatment recently, there is still much work to be done in understanding the mechanisms of migraine and how to tailor treatment to each patient,” Hay says.

topic:

Source: www.newscientist.com