Tag Archives: drugs

Why Are HIV Drugs Being Used to Treat the Coronavirus?

On Tuesday, the Japanese government announced it will begin clinical trials to test treatments for the deadly new coronavirus that’s engulfed China and spread to over two dozen countries. Rather than new drugs, they’ll be studying existing medications already used to treat HIV and other viral diseases. But why exactly are researchers hopeful that these drugs can be repurposed for the new coronavirus, and how likely are they to work?

The new coronavirus, recently named SARS-CoV-2 due to its close genetic ties to the SARS coronavirus, is made out of RNA. Other RNA viruses include the ones that cause Ebola, hepatitis C, and yes, HIV/AIDS.

RNA viruses come in all shapes and sizes, and those that infect humans can do so in different ways. But many of the drugs that go after HIV and the hepatitis C virus broadly target weaknesses found in all sorts of viruses. The approved hepatitis C drug ribavirin, for instance, interferes with something called the RNA-dependent RNA polymerase, an enzyme essential for many virusesincluding coronaviruses—to produce more of themselves inside a cell. HIV drugs like lopinavir inhibit other enzymes that allow viruses to break down certain proteins, which cripples their ability to infect cells and replicate.

Broad antiviral drugs like lopinavir should be able to work against SARS-CoV-2scientists theorize. And there’s already some circumstantial evidence they do. Some of these drugs have been successfully tested out for SARS and MERS, for instance, two other nasty coronaviruses that have emerged in recent years.

In January, the Chinese government announced a trial of 41 patients in Wuhan that would use a combination therapy of lopinavir and another HIV drug, ritonavir. In February, the Chinese government also began a trial using an experimental drug that’s been tested out for Ebola, called remdesivir.

Remdesivir has already been deployed during this outbreak, with seemingly impressive results so far. Last month, the first documented U.S. patient with the virus was treated with remdesivir, following a week of worsening symptoms that had developed into full-blown pneumonia. Within a day of receiving the drug through an IV, though, the man’s symptoms started to improve, and he was eventually released from the hospital.

But one case does not a surefire treatment make. And even if remdesivir or other drugs do prove effective against SARS-CoV-2, they’ll only play a small part in stopping this current outbreak from getting worse. Most cases of COVID-19 (the official name of the disease caused by SARS-COV-2) are still mild and won’t be helped much by antiviral drugs. In terms of preventing the next pandemic, it’s more important to keep people from getting the virus at all, rather than finding drugs to treat them once they do.

Source: https://gizmodo.com/

Nanoparticles Act As Immunotherapy Agents

University of Wisconsin–Madison researchers have developed nanoparticles that, in the lab, can activate immune responses to cancer cells. If they are shown to work as well in the body as they do in the lab, the nanoparticles might provide an effective and more affordable way to fight cancer.

They are cheaper to produce and easier to engineer than the antibodies that underlie current immunotherapies, which as drugs cost tens of thousands of dollars a month.

The nanoparticles were made of sections of the T cell protein PD-1 (in blue) attached to a branched core called a dendrimer (in gray). The branches in the core of the nanoparticle allowed many chunks of the PD-1 protein to bind to the nanoparticle, increasing its effectiveness.

Immunotherapy basically boosts the patient’s own immune system to fight against cancer cells better,” says Seungpyo Hong, a professor in the UW–Madison School of Pharmacy. “The antibodies that are used right now are large, they’re expensive, they’re hard to engineer, and they don’t always show the highest level of efficacy either. So we wanted to explore other ways to activate the immune system.

Hong and postdoctoral associate Woo-jin Jeong led the study, published online Jan. 2 in the Journal of the American Chemical Society, with collaborators at the University of Illinois at Chicago. It’s the first demonstration that nanoparticles can act as immunotherapy agents.

More research is needed to understand their effectiveness in the body, but Hong has applied for a patent on the new nanoparticles and is now testing them in animal models.

In tests against lab-grown strains of cancer, the nanoparticles boosted production of the immune stimulating protein interleukin-2 by T cells, one kind of immune cell in the body, by about 50 percent compared to no treatment. They were just as effective as antibodies. The nanoparticles were also able to improve the effectiveness of the chemotherapy drug doxorubicin in similar tests.

Normally, T cells produce a protein named PD-1 that acts like an off switch for immune responses. This “checkpoint” helps keep T cells from improperly attacking healthy cells.

Source: https://news.wisc.edu/

How To Starve Cancer Tumors and Beef Up The Immune Cells

Tumors are hogs, gobbling nutrients to fuel their runaway growth, and for decades researchers have tried to develop drugs that cut off their food supply. A study out today shows that an updated version of a failed cancer drug can not only prevent tumor cells from using an essential nutrient, but also spur immune cells to attack the growths.

T lymphocyte cells attacking a cancer cell, computer illustration. T lymphocytes are a type of white blood cell that recognise a specific site (antigen) on the surface of cancer cells or pathogens and bind to it. Some T lymphocytes then signal for other immune system cells to eliminate the cell. The genetic changes that cause a cell to become cancerous lead to the presentation of tumour antigens on the cell’s surface.

It’s a pretty striking paper,” says cancer biologist Ralph DeBerardinis of the University of Texas Southwestern Medical Center in Dallas, who wasn’t connected to the study. “With a single drug, you can in effect starve the tumor and beef up the immune cells.”

Cancer cells eat to obtain molecules vital for survival and replication, but their gluttony also turns their surroundings into an acidic, oxygen-deprived moat that stymies immune cells trying to eliminate them. One of the nutrients many tumors need in abundance is the amino acid glutamine, which provides the building blocks for fabricating molecules such as DNA, proteins, and lipids. “Glutamine is incredibly important for cellular metabolism,” says immunologist Jonathan Powell of the Johns Hopkins School of Medicine in Baltimore, Maryland.

Starting in the 1950s, researchers tried to turn tumors’ glutamine dependence against them, developing drugs to block its metabolism. A bacteria-derived compound called DON, for instance, kills tumors by inhibiting several enzymes that allow cancer cells to use glutamine. In clinical trials, however, the drug provoked severe nausea and vomiting, and it was never approved.

Now, Powell and colleagues have crafted a new version of DON that may be easier to stomach. It carries two chemical groups that keep it inert until it reaches the tumor’s neighborhood. There, enzymes that normally loiter around tumors remove these molecular handcuffs, unleashing the drug on the cancerous cells. With this approach, “the vast majority of the active drug is where we want,” Powell says.

To test their new compound, he and colleagues injected four types of cancer cells into mice, inducing tumors. They then dosed some of the animals with their next-generation DON. The drug worked against all four kinds of tumors, the scientists report today in Science. In untreated mice, for example, colon cancer tumors had grown more than five times larger after about 3 weeks. But in rodents that received DON, the tumors shrank and almost disappeared. The researchers found that the drug wasn’t just throttling glutamine metabolism. It was also disrupting other aspects of the cellsbiochemistry, such as their ability to use the sugar glucose.

Source: https://www.sciencemag.org/

Edible Sensor To Check Whether Drugs Have Been Taken

An ingestible sensor that enables health workers to check that patients have taken their medication could revolutionise tuberculosis treatment, particularly in developing countries, researchers believe. New ways to ensure TB patients comply with their treatment are desperately needed. Patients with the most straightforward form of the deadly infectious disease have to take a cocktail of drugs over a six-month period – and if they fail to stick to the regime, they risk the disease returning in a drug-resistant form.

In the study, published in in the journal Plos Medicinepatients in California were given a standard TB drug alongside an “ediblesensor, coated with minerals.  When ingested, the sensor communicates with a patch attached to the patient’s torso that in turn sends a message to a mobile phone. The data is then automatically uploaded to a secure, centralised computer for a health worker to check.

To avoid high treatment drop-out rates it is recommended that patients take their medication under the supervision of a health worker in a procedure called directly observed therapy (DOT). But this is time consuming – requiring a health worker to visit the patient at work or home or vice versa – as well as costly and inconvenient. But this new “wireless observed therapy” (WOT) avoids the need for daily visits and enables the patient to take the drugs in private and at a time that suits them.

Some 77 patients, who were no longer infectious but still needed to finish their course of treatment, took part in the study, carried out by researchers at the University of California San Diego (UCSD). A third followed the standard DOT model of care and two thirds followed the novel treatment. The study showed that WOT had a 99.3 per cent accuracy rate in recording adherence to treatment and all those patients on the wireless therapy wanted to continue with it after the trial had ended. All finished treatment and were cured of TB.

Sara Browne, lead author of the study and associate professor of infectious diseases at the UCSD, said the ingestible sensor gave patients more autonomy.

The system allows patients to determine how they want to take their pills with minimum interference. It preserves the highest standards of privacy but it also enables the health system to focus on people who need the most support,” she said.

Source: http://grantome.com/
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https://www.telegraph.co.uk/

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/