The Drug Masitinib Effective in Treating COVID-19

A new University of Chicago study has found that the drug masitinib may be effective in treating COVID-19. The drug, which has undergone several clinical trials for human conditions but has not yet received approval to treat humans, inhibited the replication of SARS-CoV-2 in human cell cultures and in a mouse model, leading to much lower viral loads.

Researchers at UChicago’s Pritzker School of Molecular Engineering (PME), working with collaborators at Argonne National Laboratory and around the world, also found that the drug could be effective against many types of coronaviruses and picornaviruses. Because of the way it inhibits replication, it has also been shown to remain effective in the face of COVID-19 variants.

Inhibitors of the main protease of SARS-CoV-2, like masitinib, could be a new potential way to treat COVID patients, especially in early stages of the disease,” said Prof. Savas Tay, who led the research. “COVID-19 will likely be with us for many years, and novel coronaviruses will continue to arise. Finding existing drugs that have antiviral properties can be an essential part of treating these diseases.”

The results were published  in Science.

Source: https://pme.uchicago.edu/

New Treatment Against Covid-19

The Institut Pasteur de Lille (France) will implement the protocol to perform clinical tests of a promising treatment against Covid-19. An authorization from the National Agency for the Safety of Medicines and Health Products (ANSM) which nevertheless comes eight months after the announcement of the discovery of this molecule by the teams of researchers.

On September 29, the Institut Pasteur de Lille confirmed to 20 Minutes have found an effective molecule against Covid-19.

It remains to conduct a clinical trial to definitively validate the antiviral activity of this molecule”, then underlined a member of the research team. This molecule had already received marketing authorization from the ANSM under the name Clofoctol for a pathology other than Covid-19. It was therefore a question of “repositioning” it as a Covid-19 treatment since “the in vitro tests have shown the effectiveness of this molecule in inhibiting the replication of the virus”, assures the Institute.

The file presented by Pasteur was validated by the Committee for the Protection of Persons (CPP) and, on Thursday, it also received the approval of the ANSM.

The clinical trial to test this experimental treatment in the early management of Covid patients, double-blind against placebo” will be able to start, “all the logistics are ready”, continues at Pasteur Lille. This test will take place in Hauts-de-France, in five centers. To be able to be included in this clinical trial, it is necessary to have made “a recent positive test, to be more than 50 years old, to have at least one symptom and not to have been vaccinated”.

If the administration of the drug will be done in the different centers, the patients will not be hospitalized. The follow-up will be provided at home thanks to the collaboration of general practitioners.

Source: https://news.in-24.com/

F.D.A. Approves Alzheimer’s Drug

Aducanumab, or Aduhelm, is the first new Alzheimer’s treatment in 18 years and the first to attack the disease process. But some experts say there’s not enough evidence it can address cognitive symptomsThe Food and Drug Administration  approved the first new medication for Alzheimer’s disease in nearly two decades, a contentious decision made despite opposition from the agency’s independent advisory committee and some Alzheimer’s experts who said there was not enough evidence that the drug can help patients.

The drug, aducanumab, which will go by the brand name Aduhelm, is a monthly intravenous infusion intended to slow cognitive decline in people with mild memory and thinking problems. It is the first approved treatment to attack the disease process of Alzheimer’s instead of just addressing dementia symptoms. Biogen, its manufacturer, announced that the list price would be $56,000 a year. In addition, there will most likely be tens of thousands of dollars in costs for diagnostic testing and brain imaging. Recognizing that clinical trials of the drug had provided incomplete evidence to demonstrate effectiveness, the F.D.A. granted approval for the drug to be used but required Biogen to conduct a new clinical trial. If the new trial, called a Phase 4 trial, fails to show the drug is effective, the F.D.A. can — but is not required to — rescind its approval.

About six million people in the United States and roughly 30 million globally have Alzheimer’s, a number expected to double by 2050. Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages. Patient advocacy groups had lobbied vigorously for approval because there are so few treatments available for the debilitating condition. Some other drugs in clinical trials are more promising, but they are most likely three or four years away from potential approval.

The F.D.A. advisory committee, along with an independent think tank and several prominent experts — including some Alzheimer’s doctors who worked on the aducanumab clinical trials — said the evidence raised significant doubts about whether the drug is effective. They also said that even if it could slow cognitive decline in some patients, the benefit suggested by the evidence would be so slight that it would not outweigh the risk of swelling or bleeding in the brain that the drug caused in the trials.

The data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit,” the F.D.A.’s director of the Center for Drug Evaluation and Research, Dr. Patrizia Cavazzoni, wrote on the agency’s website. But, she said, the agency had decided to approve the drug through a program called accelerated approval, which is designed “to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.” Michel Vounatsos, Biogen’s chief executive, hailed the approval and said in a statement, “We are committed to sharing our future insights about Aduhelm with the scientific community as we collect more data from the real-world use of this treatment.

Source: https://www.nytimes.com/

‘Game-Changer’ Drug Promotes Weight Loss Like No Medicine Ever Seen

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.

Source: https://www.ucl.ac.uk/

Colchicin-based Anti COVID treatment Reduces Deaths by 44%

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.

https://montreal.ctvnews.ca/

Nanomicelles Are Perfect Carrier To Destroy Cancerous Cells

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.

https://www.thehindu.com/

How To Lure Stem Cells To A Specific Location Without Causing Inflammation

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).

Source: https://www.genengnews.com/

Reprogramming Blood Cells To Fight Against COVID-19

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 lungs, computer illustration.

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.

Source: https://www.genengnews.com/

“Shock And Kill” Strategy To Eliminate HIV

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.”

Source: https://www.genengnews.com/

New Cancer Drug Halts Tumour Growth

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 repairBlocking 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 onetrial, 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 chemotherapyChemotherapy 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.

Source: https://www.bbc.com/