Tag Archives: drug
One third (35%) of people who took a new drug for treating obesity lost more than one-fifth (≥20%) of their total body weight, according to a major global study involving University College London (UCL) researchers. The findings from the large-scale international trial, published in the New England Journal for Medicine, are being hailed as a “game changer” for improving the health of people with obesity and could play a major part in helping the UK to reduce the impact of diseases, such as COVID-19.
The drug, semaglutide, works by hijacking the body’s own appetite regulating system in the brain leading to reduced hunger and calorie intake. Rachel Batterham, Professor of Obesity, Diabetes and Endocrinology who leads the Centre for Obesity Research at UCL and the UCLH Centre for Weight Management, is one of the principal authors on the paper which involved almost 2,000 trial participants in 16 countries.
“The findings of this study represent a major breakthrough for improving the health of people with obesity. Three quarters (75%) of people who received semaglutide 2.4mg lost more than 10% of their body weight and more than one-third lost more than 20%. No other drug has come close to producing this level of weight loss – this really is a game changer. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” said Professor Batterham (UCL Medicine).
Professor Batterham added: “The impact of obesity on health has been brought into sharp focus by COVID-19 where obesity markedly increases the risk of dying from the virus, as well as increasing the risk of many life-limiting serious diseases including heart disease, type 2 diabetes, liver disease and certain types of cancers. This drug could have major implications for UK health policy for years to come.”
The average participant in the trial lost 15.3kg (nearly 3 stone); this was accompanied by reductions in risk factors for heart disease and diabetes, such as waist circumference, blood fats, blood sugar and blood pressure and reported improvements in their overall quality of life.
A team of researchers from the Montreal Heart Institute believe they have found an effective weapon against COVID-19: colchicine, an oral tablet already known and used for other diseases. For Dr. Jean-Claude Tardif, who led the study, this is a “major scientific discovery,” he said. Colchicine is the first “effective oral drug to treat out-of-hospital patients.” As colchicine is a well-understood drug, it could be used very quickly to treat people with COVID-19, the researcher says.
“Colchicine is old as it is — we’ve been treating gout with it for hundreds of years — so it’s available in pharmacies,” Tardif said, speaking in French. “So any doctor, tomorrow, who reads this can definitely decide to prescribe if he wants.”
Analysis of the study found that colchicine resulted in reductions in hospitalizations by 25 per cent, the need for mechanical ventilation by 50 per cent, and deaths by 44 per cent.
With the advance in nanotechnology, researchers across the globe have been exploring how to use nanoparticles for efficient drug delivery. Similar to nanoshells and nanovesicles, nanomicelles are extremely small structures and have been noted as an emerging platform in targeted therapy. Nanomicelles are globe-like structures with a hydrophilic outer shell and a hydrophobic interior. This dual property makes them a perfect carrier for delivering drug molecules.
Now a multi-disciplinary, multi-institutional team has created a nanomicelle that can be used to deliver a drug named docetaxel, which is commonly used to treat various cancers including breast, colon and lung cancer.
Modus operandi: Once injected intravenously, these nanomicelles can easily escape the circulation and enter the solid tumours.
“The ideal goal for cancer therapy is destroying the cancer cells without harming healthy cells of the body, and chemotherapeutics approved for treatment of cancer are highly toxic. The currently used docetaxel is a highly hydrophobic drug, and is dissolved in a chemical mixture (polysorbate-80 and alcohol). This aggravates its toxic effects on liver, blood cells, and lungs. So, there was an urgent and unmet need to develop effective drug delivery vehicles for docetaxel without these side effects,” explains Avinash Bajaj, from the Laboratory of Nanotechnology and Chemical Biology at the Regional Centre for Biotechnology, Faridabad. He is one of the corresponding authors of the paper recently published in Angewandte Chemie.
The nanomicelles are less than 100nm in size and are stable at room temperature. Once injected intravenously these nanomicelles can easily escape the circulation and enter the solid tumours where the blood vessels are found to be leaky. These leaky blood vessels are absent in the healthy organs. “Chemical conjugation would render the phospholipid-docetaxel prodrug to be silent in the circulation and healthy organs. But once it enters the cancer cells, the enzymes will cleave the bond to activate the drug, and kill the cancer cells,” adds Dr. Bajaj.
The team tested the effectiveness of the nanomicelles in a mice breast tumour model and was found to help in tumour regression. Its toxicity was compared with the currently used FDA approved formulation and found to be less toxic. Similar promising results were seen when tested in higher model organisms including rats, rabbits and rhesus monkeys.
Transplanted stem cells instigate healing only after they reach a repair site, or “pathologic niche.” To help transplanted stem cells find their way, scientists have considered exploiting a natural inflammo-attraction system. It guides stem cells to inflammatory signals emitted by damaged tissue. The system, however, has usually been deemed too hot, that is, too apt to worsen inflammation and harm the body.
If only it were possible to shed the “inflammo” part of inflammo-attraction. Then, therapeutic stem cells could be deployed like smart bombs—except that they’d provide more balm than blam.
Neural stem cells maturing into astrocytes (yellow). [Sanford Burnham Prebys Medical Discovery Institute]
The possibility has been investigated by scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP). In a recent study, they reported that they modified an inflammatory “homing” molecule to create a drug that enhances stem cell binding and minimizes inflammatory signaling. They assert that this drug, which is called SDV1a, can be injected anywhere to lure stem cells to a specific location without causing inflammation.
Details appeared online in the Proceedings of the National Academy of Sciences (PNAS).
Scientists report that they have successfully created airway basal stem cells in vitro from induced pluripotent stem cells by reprogramming blood cells taken from patients. Given that airway basal cells are defined as stem cells of the airways because they can regenerate the airway epithelium in response to injury, this study may help accelerate research on diseases impacting the airway, including COVID-19, influenza, asthma, and cystic fibrosis, according to the team led by researchers at the Center for Regenerative Medicine at Boston Medical Center and Boston University (CReM), in collaboration with the University of Texas Health Science Center at Houston (UTHealth).
These findings represent a critical first step towards airway regeneration, which will advance the field of regenerative medicine as it relates to airway and lung diseases, added the scientists.
The study, “Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells,” published in Cell Stem Cell, outlines how to generate and purify large quantities of airway basal stem cells using patient samples. This allows for the development of individual, disease-specific airway basal stem cells in a lab that can be used to develop disease models, which may ultimately lead to drug development and a platform in which targeted drug approaches can be tested.
The study’s findings and cells will be shared freely given the CReM’s “Open Source Biology” philosophy, or sharing of information and findings that will help advance science across the globe.
Human Airway Basal Stem Cells
“The derivation of tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would have broad reaching implications for regenerative medicine. Here, we report the directed differentiation of human iPSCs into airway basal cells (iBCs), a population resembling the stem cell of the airway epithelium,” the investigators wrote.
“Simply put, we have developed a way to reproduce patient-specific airway basal cells in the lab, with the ultimate goal of being able to regenerate the airway for patients with airway diseases,” said Finn Hawkins, MB, a pulmonologist and physician-scientist at Boston Medical Center, principal investigator in the CReM and the Pulmonary Center, and the study’s first author.
“These results could lead to a better understanding, and therefore treatments for, a variety of airway diseases,” noted Shingo Suzuki, PhD, co-first author and post-doctoral researcher at UTHealth. For example, cystic fibrosis is caused by a genetic mutation that is present in all of the airway cells. “If we could make pluripotent stem cells using a sample from a patient who has cystic fibrosis, correct the mutation and replace the defective airway cells with corrected airway basal cells that are otherwise genetically identical, we might eventually be able to cure the disease, and other diseases in the future using this same technology,” added Hawkins.
When therapeutics battle HIV, they tend to miss pockets of resistance where HIV can hunker down until it stages a comeback. HIV, then, cannot be defeated until its remnants are roused to action, and its hiding places exposed and eliminated. This two-step strategy is called “shock and kill.” It sounds promising, but shock and kill hasn’t quite worked yet. It still needs the right shock.
Encouragingly, a better shock has been proposed by scientists at Sanford Burnham Prebys Medical Discovery Institute. These scientists, led by Sumit Chanda, PhD, director and professor and Nicholas Cosford, PhD, deputy director of the NCI-designated Cancer Center at Sanford Burnham Prebys and co-senior author of the study, have identified a drug that reawakens the virus without activating the immune system. That is, the drug makes it possible to save the immune system without having to destroy it.
“What scientists have found with other ‘shock’ approaches is that they can be too hot and overactivate the immune system, or too cold and don’t wake up the virus,” said Chanda. “Our research identifies a drug that works in the ‘Goldilocks’ zone.”
The drug is a Smac mimetic called Ciapavir (SBI-0953294). Smac mimetics are a class of small-molecule peptidomimetics derived from a conserved binding motif of Smac (second mitochondria-derived activator of caspases), an endogenous protein inhibitor of apoptosis. Originally developed as cancer drugs, Smac mimetics are being evaluated for other purposes, such as fighting HIV.
Repurposed Smac mimetics have had modest success in reversing HIV latency. In hopes of building on this success, Chanda, Cosford, and colleagues decided to experiment with a Smac mimetic optimized to reverse HIV latency. The results of this work appeared June 23 in Cell Reports Medicine, in an article titled, “Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs In Vivo.” According to this article, Ciapavir is more efficacious as a latency-reversing agent than other drugs of its class.
“Ciapavir induced activation of HIV-1 reservoirs in vivo in a bone marrow, liver, thymus (BLT) humanized mouse model without mediating systemic T cell activation,” the article’s authors wrote. “This study provides proof of concept for the in vivo efficacy and safety of Ciapavir and indicates that Smac mimetics can constitute a critical component of a safe and efficacious treatment strategy to eliminate the latent HIV-1 reservoir.”
A drug that could stop cancer cells repairing themselves has shown early signs of working. More than half of the 40 patients given berzosertib had the growth of their tumours halted. Berzosertib was even more effective when given alongside chemotherapy, the trial run by the Institute of Cancer Research (ICR) and the Royal Marsden NHS Trust in UK suggested. The trial was designed to test the safety of the drug. The drug is the first to be trialled of a new family of treatments, which block a protein involved in DNA repair. Blocking this protein prevents cancers from mending damage to their cells. It’s part of a branch of treatment known as “precision medicine“, which targets specific genes or genetic changes.
The study involved patients with very advanced tumours, for whom no other treatment had worked. This was what is known as a “phase one” trial, which is only designed to test the safety of a treatment. But the ICR said the researchers did find some early indications that berzosertib could stop tumours growing. One of the study’s authors, Prof Chris Lord, a professor of cancer genomics at the ICR, said these early signs were “very promising”, adding that it was unusual in phase one trials to see a clinical response. Further trials will be needed to demonstrate the drug’s effectiveness, though.
“This study involved only small numbers of patients…Therefore, it is too early to consider berzosertib a game changer in cancer treatment,” said Dr Darius Widera at the University of Reading. “Nevertheless, the unusually strong effects of berzosertib, especially in combination with conventional chemotherapy, give reasons to be optimistic regarding the outcomes of follow-up studies.”
One patient in the trial, with advanced bowel cancer, had his tumours completely disappear after treatment with berzosertib, and has remained cancer-free for two years. Another, whose ovarian cancer returned following a different course of treatment, saw her tumours shrink after combination treatment with the drug and chemotherapy. Chemotherapy works by damaging cancer cells’ DNA, so using it in conjunction with this new treatment, which stops the cells from repairing themselves, appears to give an even greater benefit. And berzosertib is able to target tumour cells without affecting other healthy cells, Prof Lord said.
“Our new clinical trial is the first to test the safety of a brand-new family of targeted cancer drugs in people, and it’s encouraging to see some clinical responses even in at this early stage,” said Professor Johann de Bono, head of drug development at the ICR and the Royal Marsden.
The steroid dexamethasone has been found to reduce the risk of death in seriously illpatients by about a third, according to clinical trial results hailed on Tuesday as a “major breakthrough.” The drug did not appear to help less severely ill patients.
Researchers led by a team from the University of Oxford administered the inexpensive, widely available drug to more than 2,000 severely ill COVID-19 patients. Among those who could only breathe with the help of a ventilator, dexamethasone reduced deaths by 35%. It reduced deaths by about 20% among patients who were receiving oxygen only, according to preliminary results.
Dexamethasone is an anti-inflammatory drug normally used to treat a range of allergic reactions as well as rheumatoid arthritis and asthma.
An experimental COVID-19 vaccine protected monkeys from catching the viral infection, according to an unreviewed report. The new vaccine has now entered clinical trials in China to test the drug in humans.
Although the animal study, posted April 19 to the preprint database bioRxiv, has not been subject to formal review, scientists took to Twitter to share their first impressions.
“So, this is the first ‘serious’ preclinical data I have seen for an actual vaccine candidate,” Florian Krammer, a professor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, tweeted on April 22. Before being tested in healthy humans, vaccines undergo so-called preclinical tests in animals. The experimental vaccine, developed by the Beijing-based company Sinovac Biotech, showed promising results in rhesus macaques before entering human trials, Krammer noted. “I’m a fan,” he added in another tweet.
Now in clinical trials, various doses of the vaccine will be given to 144 individuals to determine whether it’s safe, meaning it does not cause dangerous side effects, according to ClinicalTrials.gov. The vaccine would then move into efficacy trials with more than 1,000 additional people to determine whether it triggers an adequate immune response, commented Meng Weining, Sinovac’s senior director for overseas regulatory affairs.
The Sinovac vaccine contains an inactivated version of SARS-CoV-2, the virus that causes COVID-19. By introducing an inactive virus into the body, the vaccine should prompt the immune system to build antibodies that target the pathogen without triggering an actual COVID-19 infection. When given to mice, rats and rhesus macaques, the vaccine sparked the production of such antibodies, according to the bioRxiv report. “This is old-fashioned technology,” which would make the product easy to manufacture, Krammer wrote on Twitter. “What I like most is that many vaccine producers, also in lower–middle-income countries, could make such a vaccine,” he added in an interview