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Disarming the immune system’s lethal lung response

Neutrophils, the most abundant type of white blood cell, are the body’s first line of defense against infection. Foreign pathogens can stress the body…

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Neutrophils, the most abundant type of white blood cell, are the body’s first line of defense against infection. Foreign pathogens can stress the body and activate neutrophils. When activated, neutrophils employ various weapons to protect the body. But if overactivated, these weapons can damage the body’s own tissues. Lung tissue is saturated with blood vessels, making them very susceptible to neutrophil attacks. If severe enough, acute lung injuries can lead to acute respiratory distress syndrome (ARDS), the leading cause of death due to COVID-19.

Credit: Tonks lab/CSHL, 2022

Neutrophils, the most abundant type of white blood cell, are the body’s first line of defense against infection. Foreign pathogens can stress the body and activate neutrophils. When activated, neutrophils employ various weapons to protect the body. But if overactivated, these weapons can damage the body’s own tissues. Lung tissue is saturated with blood vessels, making them very susceptible to neutrophil attacks. If severe enough, acute lung injuries can lead to acute respiratory distress syndrome (ARDS), the leading cause of death due to COVID-19.

Nicholas Tonks, Caryl Boies professor of cancer research at Cold Spring Harbor Laboratory (CSHL), and his team have found a drug candidate that can prevent lethal lung inflammation in mice by inhibiting a protein called PTP1B. Their discovery may help develop better treatments for severe inflammatory conditions like sepsis and COVID-19.

“When you think about COVID-19, acute lung injury and ARDS underlie the fatal aspects of the disease,” Tonks says. “And so, when the pandemic took hold, we were wondering whether there was anything we could do to help, to provide an understanding of this aspect of the disease and suggest ways it could be treated.”

Tonks’ graduate student Dongyan Song investigated whether using a PTP1B inhibitor drug candidate could dampen the lethal consequences of overactive neutrophils in mice. She found that pretreating mice with the PTP1B inhibitor reduced lung tissue damage. When untreated, less than half of the mice survived acute lung injuries and ARDS. But when pretreated, they all survived. 

The researchers exploited a natural process, called neutrophil aging, that the body uses to control the immune cell’s lifespan. As they age, neutrophils become less dangerous. Tonks’ team discovered PTP1B inhibition speeds up neutrophil aging. “An aged neutrophil is like a soldier without a weapon,” Song explains. “So regardless of how many neutrophils flood an area, they won’t be able to do serious damage.”

This project was part of a program of COVID-related research at CSHL. Tonks says collaborations with CSHL Professor Mikala Egeblad, postdoc Jose M. Adrover, and CSHL Research Associate Professor Scott Lyons were essential to this discovery. Going forward, he and Song are working to increase the understanding of how PTP1B inhibitors affect the immune system. Tonks hopes his lab’s continued research leads to new treatments and preventative measures for various inflammatory diseases. His lab is currently working with DepYmed, Inc. to take PTP1B inhibitor drug candidates into clinical trials. 

Tonks’ lab studies signal transduction, the process that controls how cells respond to signals from their environment. In particular, they focus on the PTP protein family, which Tonks discovered over 30 years ago. Since then, he’s sought to develop small molecule drug candidates that target these proteins, which can provide new approaches for treating major human diseases including cancer and metabolic and neurodegenerative diseases.


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Revive Therapeutics To Re-Apply For Primary Endpoint Change With The FDA

Today, Revive Therapeutics Ltd. (CNSX: RVV) (OTCMKTS: RVVTF) provided an update to investors pertaining to its current Phase 3 clinical trial to evaluate…

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Today, Revive Therapeutics Ltd. (CNSX: RVV) (OTCMKTS: RVVTF) provided an update to investors pertaining to its current Phase 3 clinical trial to evaluate the safety and efficacy of Bucillamine to treat COVID-19. If the desired outcome is successful, it could remediate last week’s FDA decision and set the trial on a positive trajectory once again.

Following the company’s recent submission of amended protocol to the FDA—in which endpoints related to time to resolution using the polymerase chain reaction (PCR) test was not accepted—Revive Therapeutics has charted a different path.

It now will submit a revised primary efficacy protocol assessing the difference between participants with at least two clinical improvements in symptoms of COVID-19 at Day 14, compared with baseline between Bucillamine versus placebo. Time to resolution via PCR test now becomes a secondary endpoint—among others—instead of the primary. Ultimately, Revive gets another shot at approval through better refinement and optimization of new endpoint protocols.

Endpoint change sought be Revive Therapeutics to a symptoms focus from hospitalization/death remains in play

Should the FDA agree with the revised protocol, the company’s Data Safety Monitoring Board (DSMB) will review the post-dose data compilation of approximately 500 subjects in the context of the new primary endpoint. From there, the committee shall offer one of several possible courses of action:

• Make a recommendation on continuing the study by enrolling additional patients

• Advise on halting the study early due to positive efficacy showing statistical significance

• Recommend halting the trial due to lack of safety and/or efficacy

Revive expects to submit the revised protocol sometime next week.

In response to today’s news, shares of Revive Therapeutics partially reversed the big-volume downside move experienced on September 28. RVV rallied +47.62% to $0.31 per share on the Canadian Stock Exchange, as traders bought the recent discount given that FDA endpoint approval is still very much in-play.

TDR will have further coverage as warranted.

The post Revive Therapeutics To Re-Apply For Primary Endpoint Change With The FDA appeared first on The Dales Report.

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Hundreds Of Thousands Of Americans Sought Medical Care After COVID-19 Vaccination: CDC Data

Hundreds Of Thousands Of Americans Sought Medical Care After COVID-19 Vaccination: CDC Data

Authored by Zachary Stieber via The Epoch Times…

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Hundreds Of Thousands Of Americans Sought Medical Care After COVID-19 Vaccination: CDC Data

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

Hundreds of thousands of Americans sought medical care after getting a COVID-19 vaccine, according to Centers for Disease Control and Prevention (CDC) data released on Oct. 3.

The Center for Disease Control (CDC) headquarters in Atlanta, Ga., in a file photograph. (Jessica McGowan/Getty Images)

Some 782,900 people reported seeking medical attention, emergency room care, and/or hospitalization following COVID-19 vaccination. Another 2.5 million people reported needing to miss school, work, or other normal activities as a result of a health event after getting a COVID-19 vaccine.

The reports were made to the CDC’s V-safe program, a new vaccine safety monitoring system to which users can report issues through smartphones.

The CDC released the data to the Informed Consent Action Network (ICAN) after being sued over not producing the data when asked by the nonprofit. ICAN posted a dashboard summarizing the data.

It took numerous legal demands, appeals, and two lawsuits, and over a year, but the CDC finally capitulated and agreed to a court order requiring them to do what they should have done from day one, release the V-safe data to the public,” Aaron Siri, a lawyer representing ICAN in the case, told The Epoch Times in an email.

About 10 million people utilized V-safe during the period of time the data covers: Dec. 14, 2020, to July 31, 2022. About 231 million Americans received at least one vaccine doses during that time.

The V-safe users reported about 71 million symptoms.

The most commonly reported symptoms were chills (3.5 million), swelling (3.6 million), joint pain (4 million), muscle or body aches (7.8 million), headache (9.7 million), fatigue (12.7 million), and general pain (19.5 million).

About 4.2 million of the symptoms were of severe severity.

Users of V-safe filled in data for about 13,000 infants younger than two, reporting over 33,000 symptoms, including pain, loss of appetite, and irritability.

The data produced so far by the CDC does not include free-text responses, according to ICAN. The data covered fields where users checked boxes.

ICAN, founded by film producer Del Bigtree, said that the newly revealed data “reveals shocking information that should have caused the CDC to immediately shut down its COVID-19 vaccine program,” citing the percentage of people who reported needing to get care or missing school, work, or other normal activities, as well as the reported adverse events.

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Tyler Durden Thu, 10/06/2022 - 18:20

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Washington Gave $28M To Chinese Entities For Joint Research Since 2015: Report

Washington Gave $28M To Chinese Entities For Joint Research Since 2015: Report

Authored by Rita Li via The Epoch Times (emphasis ours),

Recently…

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Washington Gave $28M To Chinese Entities For Joint Research Since 2015: Report

Authored by Rita Li via The Epoch Times (emphasis ours),

Recently released findings show U.S. government agencies sent over $28 million in taxpayers’ dollars “directly to Chinese entities” for joint research over a five-year period ending 2021.

A technician works at a DNA tech lab in Beijing on Aug. 22, 2018. (Greg Baker/AFP/Getty Images)

From fiscal years 2015 through 2021, “the CDC [Centers for Disease Control and Prevention], NIH [National Institutes of Health], and DOD [Department of Defense] provided 22 awards totaling $28.9 million directly to Chinese entities including universities and other research institutions,” the Government Accountability Office (GAO) said on Sept. 29 following a trove of analyses.

Researchers found the federal funding focused on “multiple scientific disciplines,” aiding Chinese entities in conducting research on “disease surveillance, vaccination studies, and the development of new drugs,” as well as “alternative technologies to propel vehicles such as drones.”

The release of its 38-page report (pdf) follows a January request from House Republican Conference Chairwoman Elise Stefanik (R-N.Y.) and Michael McCaul (R-Texas), the top Republican on the House Foreign Affairs Committee. They asked GAO to review federal funds provided to China or entities controlled by the Chinese Communist Party (CCP) for collaborative research, and U.S. contributions to multilateral institutions.

Stefanik described such funding as “troubling.”

“China’s deception and stonewalling of the truth behind the origins of COVID-19 has led to millions of senseless deaths and trillions of dollars in economic destruction across the globe,” the congresswoman said in a statement to The Epoch Times.

The three agencies awarded a total of 13 Chinese entities for joint publications, information sharing, and workshops, while 84 percent of the direct funding went to the University of Hong Kong, Peking University, and the Chinese Center for Disease Control and Prevention, known as the Chinese CDC.

Receiving almost $5 million from the NIH and the CDC over the past years, the Chinese CDC had been suppressing information about the outbreak domestically and snubbed U.S. offers of assistance, despite how any health data would have been crucial to formulate a more effective COVID-19 containment strategy and minimize the disease’s global spread.

Health workers wearing personal protective equipment walk on a street in a neighborhood during a COVID-19 lockdown in the Jing’an district in Shanghai on April 8, 2022. (Hector Retamal/AFP via Getty Images)

“Even more frightening,” Stefanik continued, “we still have no idea how much total money has been sent to China due to lax reporting requirements. Make no mistake, the Chinese Communist Party’s deception throughout the pandemic confirmed that China is not a reliable partner.”

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Tyler Durden Thu, 10/06/2022 - 17:40

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