#Covid19Treatment; #HowCovid19AttacksHumanBody; #GlobalResearch; #cytokines
New York, Apr 18 (Canadian-Media): Development of an effective treatment or vaccine to stop the global pandemic for COVID-19 pandemic is dependent on full understanding of how COVID-19 attacks human body, and the response of humanbody, media reports said.
Coronavirus. Image credit: Twitter
n an attempt to fully understand the virus, researchers around the world are compiling and sharing their early observations of COVID-19 patients.
These findings, though preliminary, are pointers to research in the right directions.
Researchers have observed that in severe cases, COVID-19 our respiratory cells are attacked triggering an immune system response targeting those infected cells.
This occurrence leads to the destruction of lung tissues, clogs our airways and cuts off oxygen supply, and ultimately in organs failure.
The organs most at risk of damage were found to be kidney heart.
It is yet to be researched by them if the organs or being shut down of in a new way or it is similar other infections that cause such common complications.
The deadliness of the virus can be determined by how our body responds to fight the virus when the body is infected by it.
Cytokines, released by the immune system, to co-ordinates an immune response against an infection or injury, but sometimes the infection causes the overproduction of these rampage through the bloodstream and severely damage the body.
Dr. Douglas Fraser, an ICU doctor at London Health Sciences Centre and a researcher at Western University in London, Ont., said there are different types of cytokines released in the body at unusual times in all of the very sick patients: requiring the ICU admissions, and those having difficulty breathing and those that are ultimately dying.
The researchers said after understanding of what's going on, therapies and vaccines can be developed.
#ColumbiaUniversity; #NewYork; #Schizophrenia;
New York, Apr 16 (Canadian-Media): For the first time in decades, researchers may have a new way to tweak brain signals to treat psychosis and other symptoms of schizophrenia, https://www.sciencemag.org/news.
Results from a 245-person clinical trial hint that a compound called SEP-363856, which seems to act on neural receptors involved in dopamine signaling, might address a broader range of schizophrenia symptoms than currently available drugs do—and with fewer side effects.
“If these results are confirmed, this will be big, big news,” says Jeffrey Lieberman, a psychiatrist at Columbia University. The drug’s developer, Sunovion Pharmaceuticals Inc., identified it through an unusual screening process not guided by the brain circuits and receptors already implicated in the disease, Lieberman says. “It was a big gamble on their part. This study suggests that it may pay off.”
The biological basis of schizophrenia remains a puzzle, but researchers have linked patients’ hallucinations and delusions to an excess of the chemical messenger dopamine. To inhibit dopamine signaling, existing antipsychotic drugs bind to a type of dopamine receptor on neurons called D2. These drugs help control abnormal perceptions and thoughts—the “positive” symptoms of schizophrenia. But they don’t do much to address either cognitive impairments or the “negative” symptoms, including lack of motivation, dulled emotion, and social withdrawal. “Those negative symptoms are often the most devastating,” says Diana Perkins, a psychiatrist at the University of North Carolina, Chapel Hill. “A person can become, at the most extreme, robotlike.”
The first generation of antipsychotic drugs that emerged in the 1950s sometimes actually worsened these negative symptoms, Perkins says. And tamping down on dopamine signaling can lead to side effects including tremors and other involuntary movements. A second generation of D2-targeting drugs has reduced the risk of some of these side effects, but many cause weight gain and other metabolic problems.
Sunovion started its drug search wanting to avoid D2 receptors. “It was a bit of an antitarget approach,” says Kenneth Koblan, the company’s chief scientific officer. “If [a compound] worked through the D2 system, we didn’t want to work on it.” The researchers relied on a drug screening method, developed by PsychoGenics Inc., that used artificial intelligence to analyze the behavior of mice exposed to hundreds of candidate compounds. The researchers looked for a compound that mimicked the effects of D2-targeting drugs. One stage of the testing involved trying to reverse the effects phencyclidine, better known as PCP, which causes hyperactivity and other schizophrenialike behaviors.
SEP-363856 rose to the top of the heap. This compound didn’t touch D2 receptors, the researchers found, but it activated two other types of neural receptors—known as TAAR1 and 5-HT1A—that help regulate the synthesis and release of dopamine. The mechanisms of the drug aren’t fully clear, but the researchers suspect they’ve hit on a new way to tweak dopamine signaling.
The clinical trial tested SEP-363856’s effects in people who were still early in the course of schizophrenia—none had been hospitalized for acute psychotic symptoms more than twice. During a flare-up of these symptoms, the participants, who ranged from 18 to 40 years old, spent 4 weeks in the hospital taking either SEP-363856 or an identical-looking placebo pill once a day. Clinicians then evaluated a broad set of schizophrenia symptoms using a measure called the Positive and Negative Syndrome Scale (PANSS), which gives scores ranging from 30 to 210, with a higher score representing worse symptoms. On average, participants scored roughly 100 on entering the study; after 4 weeks, the average score in the drug group had dropped by 17.2 points, versus 9.7 in the placebo group, the researchers report today in The New England Journal of Medicine.
“This is great news,” says Romina Mizrahi, a psychiatrist at the University of Toronto. The trial didn’t directly compare SEP-363856 to other drugs, but she notes that the reduction in PANSS scores is similar to results from some trials of now-approved antipsychotic drugs.
The group taking SEP-363856 also had a larger drop than the placebo group on another scale, one meant to measure negative symptoms like lack of pleasure and motivation. Though the study wasn’t statistically designed to draw conclusions using this secondary measure, this early indication “is a big deal, and it’s potentially a game changer,” Perkins says. “If it’s confirmed … that would mean a lot for many patients and their families.”
Rates of side effects, including movement disorders, nausea, agitation, and drowsiness, were low in both groups. And although SEP-363856’s long-term effects on metabolism aren’t clear, the compound didn’t cause major weight gain in either the 4-week trial or a 26-week extension that included 156 of the participants, all of whom got the experimental drug.
Sunovion isn’t the only company looking to sidestep D2 receptors in treating schizophrenia. Karuna Therapeutics is studying xanomeline, a compound with a different neural target, which Eli Lilly developed in the 1990s and later abandoned after finding that many patients experienced side effects that include nausea and dizziness. (Karuna aims to reduce those effects by combining xanomeline with another drug.) The company announced positive results from a study involving 182 patients last year.
In September 2019, Sunovion launched a larger, phase III trial that will include more than 1000 people, designed to prove the drug’s efficacy and win regulatory approval. Koblan says he can’t estimate when the trial might yield results, citing COVID-19. “I would be very comfortable answering that question if we weren’t in the midst of a pandemic,” he says.
#Covid19PandemicVaccine; #Research; #RedTape; #ScietificEvidence; Ethics; #ClinicalTrials
New York, Apr 16 (Canadian-Media): In an effort to end the humanity's lockdown globally, accelerated efforts are being made by at least 70 research teams, including some in Canada, to develop a potential pandemic vaccines within a year by bypassing some of the usual red tape that slows down the vaccine approval process, media reports said.
Pandemic Vaccine Research. Image credit: Twitter
Scientists said the goal of the vaccine is to expose our immune system to part of the virus so our antibody fighters can prepare to attack the virus that causes COVID-19, since in a pandemic, no one has immunity to the virus because it is new.
Dr. Scott Halperin, of the Canadian Immunization Research Network, stressed the importance to have multiple versions of the vaccine that achieve the same purpose but work in different ways.
He said with the first phase of clinical trials focused on safety, with about 30 to 50 volunteers testing out different doses of shots, next step of Phase 2 trials is critical as it involves larger number of people and takes about from seven to 10 years normally for the vaccine to go from the lab to the arms of patients.
"What's mainly being accelerated are the various administrative steps, not the safety steps," he said and added Canadian researchers hope to have some potential vaccines in clinical trials within the next four to six weeks.
However, Jonathan Kimmelman, a biomedical ethics professor at McGill University in Montreal, who watches both scientific and ethical standards are followed was concerned that in a hurry to develop a vaccine, we may be tempted to tolerate less than optimal science and said,
"That to me seems unacceptable. The stakes are just as high right now in a pandemic as they are in non-pandemic settings."
To show how long the process can take, Kimmelman points to the example of the ongoing search for an effective HIV vaccine that began in the 1990s
In the meantime second phase of testing a vaccin, adapted from the company's Ebola research is being started by China's CanSino Biologics, according to China's Ministry of Science and Technology. Still another vaccine candidate is in Phase 1.
In the U.S., Pennsylvania-based Inovio Pharmaceuticals began last week a Phase 1 trial of its vaccine candidate that uses the DNA sequence extracted from the key spike protein of SARS-CoV-2, the virus that causes COVID-19.
Earlier this week, the first person received a second dose of another potential U.S. vaccine from the National Institutes of Health (NIH) and Massachusetts-based biotech company Moderna Inc.
#U.S.; #Johnson&Johnson; #JansenDivision; #DevelopmentOfVaccine; #Coronavirus
New York, Apr 1 (Canadian-Media): A commitment of $456 million has been made by the U.S. government, through the Biomedical Advanced Research and Development Authority (BARDA) for the development of a vaccine against the new coronavirus with Johnson & Johnson (J&J)'s commitment to match roughly an equal amount by its Janssen division effort in development of the vaccine, media reports said.
Johnson & Johnson. Image credit: Twitter
Built around an engineered version of adenovirus 26 (Ad26), Janssen’s vaccine, which normally causes common colds has been disabled to replicate.
Same Ad26 platform has been tested against Ebola, HIV, respiratory syncytial virus, and Zika. J&J last year had $42 billion in pharmaceutical sales.
Company scientists stich into this Ad26 “vector” a gene for the surface protein from the new coronavirus spreading around the world.
Although skepticism about its advantage over pharmaceutical companies was raised by Florian Krammer, a researcher at the Icahn School of Medicine at Mount Sinai, who has co-authored a status report in Immunity about the COVID-19 vaccine, Paul Stoffels, J&J’s chief scientific officer and a veteran HIV drug developer said the effort will be nonprofit and the vaccine will be accessible to all through some global mechanism still to be determined.
J&J also said that staffed by 50,000 people, it can make 300 million vaccines, in a 2000-liter vessel, on an annual basis and that testing on animals is being done with criteria to neutralizing antibodies.
With 4000 people in clinical research all over the world, J&J hopes to launch its large phase II study in six weeks and by early winter the vaccine could ready for that large trial at Northern Hemisphere in the temperate regions.