Tag Archives: treatment

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