Tag Archives: drugs

Reverse biological aging

In a small clinical trial, scientists were looking for a means to restore the thymus — the gland that forms and releases key immune cells. By doing so, they actually managed to reverse various aspects of biological aging. The thymus gland, located between the lungs, is the organ within which T cells — a critical population of immune cells — mature. This gland also has a peculiarity. After a person reaches puberty, it begins a process of involution, which means that it becomes less and less active and starts to shrink in size gradually. Studies have shown that thymic involution affects the size of immune cell populations related to it, possibly causing changes to biological mechanisms when people reach their 60s.

Prof. Steve Horvath from the University of California Los Angeles School of Public Health and colleagues initially set out to see if they could restore function in the aging thymus.

Thymic involution leads to the depletion of critical immune cell populations, […] and is linked to age‐related increases in cancer incidence, infectious disease, autoimmune conditions, generalized inflammation, atherosclerosis, and all‐cause mortalit,” he explains In the study paper recently published in the journal Aging Cell.

For the reasons outlined above, the researchers organized and conducted what they believe is a first-of-its-kind clinical trial: TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation). The study took place between 2015–2017, and the researchers were pleased with the results they achieved. They found that it was possible to restore thymic function and reduce the risk of age-related conditions and diseases linked to poor immune system reaction.

They also had a pleasant surprise. At the end of the trial, the researchers found that the mix of drugs they used to restore the thymus gland had also reversed other aspects of biological aging. A person’s biological age refers not to how old they are in conventional years, but to how much their biological mechanisms have aged, according to their epigenetic clocksmarkers that indicate how changes in various cellular mechanisms have affected gene expression.

For their trial, Prof. Horvath and team recruited 10 healthy adult males aged 51–65. The researchers were able to use and analyze data collected from nine of these individuals. In the first week of the clinical trial, the researchers gave the participants recombinant human growth hormone (rhGH). In its natural state, rhGH supports many different aspects of cellular health, such as cell growth and regeneration. Previous studies — some conducted in animals, and others with the participation of individuals with HIV — have uncovered evidence that rhGH could help restore thymus function, as well as immune system effectiveness. 

Source: https://onlinelibrary.wiley.com/
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https://www.medicalnewstoday.com/

One Pill A Day Reduces Heart Attack Risk By One Third

A cheap, single pill taken once a day that combines four common drugs is safe and reduces the risk of events such as heart attacks, strokes and sudden death in people over the age of 50, research has found. The study, the first large-scale trial to date, looked at the effectiveness of a so-called polypill – a four-in-one therapy containing drugs to lower cholesterol and blood pressure that was first proposed more than 15 years ago. The researchers found those taking the polypill had a more than 30% lower risk of serious heart problems than those just offered advice.

While different formulations have been studied, previous trials have only been conducted in small groups of people and over short periods of time. These studies have primarily looked at the impacts of cholesterol on blood pressure, relying on models to predict the impact on cardiovascular events such as strokes – meaning the full potential of the polypill has remained unclear. The latest study tackled both of these problems.

There has been a lot of talk about using this simple, fixed-dose combination drug for prevention of cardiovascular disease and I think we have shown that as a strategy it can work,” said Prof Tom Marshall, a co-author of the study from the University of Birmingham, adding that the pills might cost as little as a few pence per day. The new study involved more than 6,800 participants aged 50-75 from rural Iran – an area where almost 34% of premature deaths are down to coronary heart disease, and 14% are caused by strokes.

Writing in the Lancet, researchers from the UK, US and Iran reported that 3,417 people were given only minimum care, such as help with controlling blood pressure or cholesterol if needed, as well as lifestyle advice on topics such as diet, exercise and smoking. A similar number of people were, in addition to this, also given the polypill. More than 90% of those involved in the study did not have cardiovascular disease at the outset. Participants were followed up for five years. Over that time, 202 people taking the polypill had a major cardiovascular event, such as heart attack, heart failure, or stroke, compared with 301 in the “advice” group.

The authors say that translated as a 34% lower risk of having such an event, compared with the “advice” group, once factors including age, sex, diabetes and high blood pressure were taken into account.

There were also signs that, at least early on, the polypill reduced some aspects of high blood pressure, while it also led to a small fall in “bad” cholesterol. Both groups showed similar low levels of problematic events including internal bleeding and peptic ulcers. Overall, the results suggested that two major cardiovascular events would be avoided for every 69 people taking the tablet for 5 years. The polypill includes aspirin, which the team acknowledge is controversial as it can increase the risk of bleeding: the latest trial did not include people who were at high risk of such problems.

Source: https://www.theguardian.com/

How To Turn Breast Cancer Cells Into Fat to Stop Them From Spreading

Researchers have been able to coax human breast cancer cells to turn into fat cells in a new proof-of-concept study in mice. To achieve this feat, the team exploited a weird pathway that metastasising cancer cells have; their results are just a first step, but it’s a truly promising approach. When you cut your finger, or when a foetus grows organs, the epithelium cells begin to look less like themselves, and more ‘fluid’ – changing into a type of stem cell called a mesenchyme and then reforming into whatever cells the body needs.

This process is called epithelial-mesenchymal transition (EMT) and it’s been known for a while that cancer can use both this one and the opposite pathway called MET (mesenchymal‐to‐epithelial transition), to spread throughout the body and metastasise. The researchers took mice implanted with an aggressive form of human breast cancer, and treated them with both a diabetic drug called rosiglitazone and a cancer treatment called trametinib. Thanks to these drugs, when cancer cells used one of the above-mentioned transition pathways, instead of spreading they changed from cancer into fat cells – a process called adipogenesis.

The image  shows this process, with the cancer cells tagged with a green fluorescent protein and normal red fat cell on the left. The cancer-turned-fat cells display as brown (on the right) because the red of the fat cells combines with the green of the protein cancer cell tag.

The models used in this study have allowed the evaluation of disseminating cancer cell adipogenesis in the immediate tumour surroundings,” the team wrote in their paper, published in January 2019. “The results indicate that in a patient-relevant setting combined therapy with rosiglitazone and trametinib specifically targets cancer cells with increased plasticity and induces their adipogenesis.

Although not every cancer cell changed into a fat cell, the ones that underwent adipogenesis didn’t change back. “The breast cancer cells that underwent an EMT not only differentiated into fat cells, but also completely stopped proliferating,” said senior author Gerhard Christofori, a biochemist at the University of Basel, in Switzerland. “As far as we can tell from long-term culture experiments, the cancer cells-turned-fat cells remain fat cells and do not revert back to breast cancer cells.

So how does this work? Well, as a drug trametinib both increases the transition process of cells – such as cancer cells turning into stem cells – and then increases the conversion of those stem cells into fat cellsRosiglitazone was less important, but in combination with trametinib, it also helped the stem cells convert into fat cells. “Adipogenic differentiation therapy with a combination of rosiglitazone and [trametinib] efficiently inhibits cancer cell invasion, dissemination, and metastasis formation in various preclinical mouse models of breast cancer,” wrote the team.

Source: https://www.cell.com/
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https://www.sciencealert.com/

New Cause Of Cell Aging Discovered: Findings Have Huge Implications

New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works. The findings potentially pave the way for better cancer treatments and revolutionary new drugs that could vastly improve human health in the twilight years. The work, from Assistant Professor of Chemical Engineering and Materials Science Nick Graham and his team in collaboration with Scott Fraser, Provost Professor of Biological Sciences and Biomedical Engineering, and Pin Wang, Zohrab A. Kaprielian Fellow in Engineering, was recently published in the Journal of Biological Chemistry.

LEFT: NON-SENESCENT CELLS WERE SHOWN WITH DIFFERENT COLORS. RIGHT: SENESCENT CELLS APPEARED OFTEN WITH MULTIPLE BLUE NUCLEI AND DID NOT SYNTHESIZE DNA.

To drink from the fountain of youth, you have to figure out where the fountain of youth is, and understand what the fountain of youth is doing,” Graham said. “We’re doing the opposite; we’re trying to study the reasons cells age, so that we might be able to design treatments for better aging.”

To achieve this, lead author Alireza Delfarah, a graduate student in the Graham lab, focused on senescence, a natural process in which cells permanently stop creating new cells. This process is one of the key causes of age-related decline, manifesting in diseases such as arthritis, osteoporosis and heart disease.

Senescent cells are effectively the opposite of stem cells, which have an unlimited potential for self-renewal or division,” Delfarah said. “Senescent cells can never divide again. It’s an irreversible state of cell cycle arrest.”

The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged. “This means that the production of nucleotides is essential to keep cells young,” Delfarah said. “It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly.”

Graham’s team examined young cells that were proliferating robustly and fed them molecules labeled with stable isotopes of carbon, in order to trace how the nutrients consumed by a cell were processed into different biochemical pathways.

Scott Fraser and his lab worked with the research team to develop 3D imagery of the results. The images unexpectedly revealed that senescent cells often have two nuclei, and that they do not synthesize DNA. Before now, senescence has primarily been studied in cells known as fibroblasts, the most common cells that comprised the connective tissue in animals. Graham’s team is instead focusing on how senescence occurs in epithelial cells, the cells that line the surfaces of the organs and structures in the body and the type of cells in which most cancers arise. Graham said that senescence is most widely known as the body’s protective barrier against cancer: When cells sustain damage that could be at risk of developing into cancer, they enter into senescence and stop proliferating so that the cancer does not develop and spread.

Sometimes people talk about senescence as a double-edged sword, that it protects against cancer, and that’s a good thing,” Graham said. “But then it also promotes aging and diseases like diabetes, cardiac dysfunction or atherosclerosis and general tissue dysfunction,” he said. Graham said the goal was not to completely prevent senescence, because that might unleash cancer cells. “But then on the other hand, we would like to find a way to remove senescent cells to promote healthy aging and better function,” he explained.

Graham underscores that the team’s research has applications in the emerging field of senolytics, the development of drugs that may be able to eliminate aging cells. He said that human clinical trials are still in early stages, but studies with mice have shown that by eliminating senescent cells, mice age better, with a more productive life span. “They can take a mouse that’s aging and diminishing in function, treat it with senolytic drugs to eliminate the senescent cells, and the mouse is rejuvenated. If anything, it’s these senolytic drugs that are the fountain of youth,” Graham said. He added that in order for successful senolytic drugs to be designed, it was important to identify what is unique about senescent cells, so that drugs won’t affect the normal, non-senescent cells.

That’s where we’re coming in–studying senescent cell metabolism and trying to figure out how the senescent cells are unique, so that you could design targeted therapeutics around these metabolic pathways,” Graham added.

Source: https://viterbischool.usc.edu/
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https://eurekalert.org/

Remote-Controlled Drug Delivery Implant

People with chronic diseases like arthritis, diabetes and heart disease may one day forego the daily regimen of pills and, instead, receive a scheduled dosage of medication through a grape-sized implant that is remotely controlled.

Researchers from Houston Methodist successfully delivered continuous, predetermined dosages of two chronic disease medications using a nanochannel delivery system (nDS) that they remotely controlled using Bluetooth technology. The nDS device provides controlled release of drugs without the use of pumps, valves or a power supply for possibly up to year without a refill for some patients. This technology will be tested in space next year.

A proof-of-concept paper recently published in Lab on a Chip (online June 25) explains how the Houston Methodist nanomedicine researchers accomplished long-term delivery of drugs for rheumatoid arthritis and high blood pressure, medications that are often administered at specific times of the day or at varying dosages based on patient needs.

Nanomedicine scientists at Houston Methodist Research Institute created a remote-controlled implantable nanochannel drug delivery system (nDS) the size of a grape

We see this universal drug implant as part of the future of health care innovation. Some chronic disease drugs have the greatest benefit of delivery during overnight hours when it’s inconvenient for patients to take oral medication. This device could vastly improve their disease management and prevent them from missing doses, simply with a medical professional overseeing their treatment remotely,” said Alessandro Grattoni, Ph.D., corresponding author and chair of the department of nanomedicine at Houston Methodist Research Institute.

Grattoni and the Houston Methodist researchers have worked on implantable nanochannel delivery systems to regulate the delivery of a variety of therapies for medical issues ranging from HIV-prevention to cancer. As basic research progresses with the remote-controlled device, the Houston Methodist technology is planned for extreme remote communication testing on the International Space Station in 2020. The team hopes that one day the system will be widely available to clinicians to treat patients remotely via telemedicine. This could provide both an improvement in the patients’ quality of life and a reduction of cost to the health care system.

Source: https://www.houstonmethodist.org/

Drug To Replace Chemotherapy

A class of drugs is emerging that can attack cancer cells in the body without damaging surrounding healthy ones. They have the potential to replace chemotherapy and its disruptive side effects, reshaping the future of cancer care. The complex biological medicines, called antibody drug conjugates (ADCs), have been in development for decades, and are now generating renewed excitement because of the success of one ADC in late-stage testing, a breast cancer treatment called DS-8201.

The fervor over ADCs is such that AstraZeneca Plc in March agreed to pay as much as $6.9 billion to jointly develop DS-8201 with Japan’s Daiichi Sankyo Co., the British drugmaker’s biggest deal in more than a decade. The investment was widely seen to be a validation of DS-8201’s potential — and the ADC class of drugs as a whole — as an alternative for chemotherapy, the most widely used treatment, for some types of cancerDS-8201, which will be filed for U.S. approval by the end of September, is so well-regarded that some analysts already predict it will surpass the $7 billion in annual sales for Roche Holding AG’s breast cancer drug Herceptin, which it aims to replace.

DS-8201 may become one of the largest cancer biologic drugs,’’ said Caroline Stewart, an analyst at Bloomberg Intelligence, who estimates sales of the drug to eventually approach $12 billion globally, a level attained by only a handful of biologic drugs. “While the field has advanced and there are several companies focusing on ADCs, Daiichi in particular seems to have developed a unique expertise.

Source: https://www.bloomberg.com/

How To Kill Antibiotic-Resistant SuperBugs

A new compound which visualises and kills antibiotic-resistant superbugs has been discovered by scientists at the University of Sheffield and Rutherford Appleton Laboratory (RAL). The team, led by Professor Jim Thomas, from the University of Sheffield’s Department of Chemistry, is testing new compounds developed by his PhD student Kirsty Smitten on antibiotic resistant gram-negative bacteria, including pathogenic E. coli.

Gram-negative bacteria strains can cause infections including pneumonia, urinary tract infections and bloodstream infections. They are difficult to treat as the cell wall of the bacteria prevents drugs from getting into the microbeAntimicrobial resistance is already responsible for 25,000 deaths in the EU each year, and unless this rapidly emerging threat is addressed, it’s estimated by 2050 more than 10 million people could die every year due to antibiotic resistant infections. Doctors have not had a new treatment for gram-negative bacteria in the last 50 years, and no potential drugs have entered clinical trials since 2010.

The new drug compound has a range of exciting opportunities. As Professor Jim Thomas explains: “As the compound is luminescent it glows when exposed to light. This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at RAL.

Gram negative bacteria. Credit: University of Sheffield

“As the compound is luminescent it glows when exposed to light. This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at RAL“, explains Professor Jim Thomas. This breakthrough could lead to vital new treatments to life-threatening superbugs and the growing risk posed by antimicrobial resistance.”

The studies at Sheffield and RAL have shown the compound seems to have several modes of action, making it more difficult for resistance to emerge in the bacteria. The next step of the research will be to test it against other multi-resistant bacteria.

Source: https://www.sheffield.ac.uk/

How To Eradicate Breast Tumors In 11 Days

Despite unbelievable advances in medical science in recent decades, breast cancer kills. Approximately 1 in 8 American women will develop breast cancer cells during the course of their lifetime.

Finding a cure is imperative, and as such, fervent research continues. At the European Breast Cancer Conference in Amsterdam, scientists presented a pair of drugs with an astounding claim: this treatment can eradicate some types of breast cancer in only 11 days, eliminating the need for chemotherapy.

Chemotherapy, whilst an amazing feat of medical-scientific engineering, is known for its uncomfortable and sometimes debilitating side effects. Women undergoing chemotherapy for breast cancer treatment may lose their hair, suffer extreme fatigue, and even loss of cognitive functionCancers may also recur after long, painful months of chemotherapy treatment.

The new trial, raising hopes across the medical community, is focused upon two drugs: Herceptin and Lapatinib. The drugs, in tandem, target a protein known as HER2, which is instrumental in stimulating the growth of certain cancer cells.

A pair of drugs can dramatically shrink and eliminate some breast cancers in just 11 days, UK doctors have shown.

They both target HER2 – a protein that fuels the growth of some women’s breast cancersHerceptin works on the surface of cancerous cells while lapatinib is able to penetrate inside the cell to disable HER2.

The study, which also took place at NHS hospitals in Manchester, gave the treatment to women with tumours measuring between 1 and 3cm. But Prof Bliss believes the findings could eventually mean some women do not need chemotherapy.

In less than two weeks of treatment, the cancer disappeared entirely in 11% of cases, and in a further 17% they were smaller than 5mm.

Current therapy for HER2 positive breast cancers is surgery, followed by chemotherapy and Herceptin. But Prof Bliss believes the findings could eventually mean some women do not need chemotherapy.

Source: https://www.bbc.com

Stem Cell Therapy Could Treat Alzheimer’s And Parkinson’s

Rutgers scientists have created a tiny, biodegradable scaffold to transplant stem cells and deliver drugs, which may help treat Alzheimer’s and Parkinson’s diseases, aging brain degeneration, spinal cord injuries and traumatic brain injuriesStem cell transplantation, which shows promise as a treatment for central nervous system diseases, has been hampered by low cell survival rates, incomplete differentiation of cells and limited growth of neural connections.

So, Rutgers scientists designed bio-scaffolds that mimic natural tissue and got good results in test tubes and mice. These nano-size scaffolds hold promise for advanced stem cell transplantation and neural tissue engineering. Stem cell therapy leads to stem cells becoming neurons and can restore neural circuits.

It’s been a major challenge to develop a reliable therapeutic method for treating central nervous system diseases and injuries,” said study senior author KiBum Lee, a professor in the Department of Chemistry and Chemical Biology at Rutgers University-New Brunswick. “Our enhanced stem cell transplantation approach is an innovative potential solution.

The researchers, in cooperation with neuroscientists and clinicians, plan to test the nano-scaffolds in larger animals and eventually move to clinical trials for treating spinal cord injury. The scaffold-based technology also shows promise for regenerative medicine.

The study included researchers from Rutgers and Kyung Hee University in South Korea. The results have been published in  Nature Communications.

Source: https://www.eurekalert.org/

Spheres Trick, Trap and Terminate Water Contaminant

Rice University scientists have developed something akin to the Venus’ flytrap of particles for water remediationMicron-sized spheres created in the lab of Rice environmental engineer Pedro Alvarez are built to catch and destroy bisphenol A (BPA), a synthetic chemical used to make plasticsBPA is commonly used to coat the insides of food cans, bottle tops and water supply lines, and was once a component of baby bottles. While BPA that seeps into food and drink is considered safe in low doses, prolonged exposure is suspected of affecting the health of children and contributing to high blood pressure. The good news is that reactive oxygen species (ROS) – in this case, hydroxyl radicals – are bad news for BPA. Inexpensive titanium dioxide releases ROS when triggered by ultraviolet light. But because oxidating molecules fade quickly, BPA has to be close enough to attack. That’s where the trap comes in.

Close up, the spheres reveal themselves as flower-like collections of titanium dioxide petals. The supple petals provide plenty of surface area for the Rice researchers to anchor cyclodextrin molecules. Cyclodextrin is a benign sugar-based molecule often used in food and drugs. It has a two-faced structure, with a hydrophobic (water-avoiding) cavity and a hydrophilic (water-attracting) outer surface. BPA is also hydrophobic and naturally attracted to the cavity. Once trapped, ROS produced by the spheres degrades BPA into harmless chemicals.

In the lab, the researchers determined that 200 milligrams of the spheres per liter of contaminated water degraded 90 percent of BPA in an hour, a process that would take more than twice as long with unenhanced titanium dioxide. The work fits into technologies developed by the Rice-based and National Science Foundation-supported Center for Nanotechnology-Enabled Water Treatment because the spheres self-assemble from titanium dioxide nanosheets.

Petals” of a titanium dioxide sphere enhanced with cyclodextrin as seen under a scanning electron microscope. When triggered by ultraviolet light, the spheres created at Rice University are effective at removing bisphenol A contaminants from water.

Most of the processes reported in the literature involve nanoparticles,” said Rice graduate student and lead author Danning Zhang. “The size of the particles is less than 100 nanometers. Because of their very small size, they’re very difficult to recover from suspension in water.

The research is detailed in the American Chemical Society journal Environmental Science & Technology.

Source: http://news.rice.edu/