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Immunology

Identifying emerging diseases focus of new international collaboration – Washington University School of Medicine in St. Louis

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School of Medicine to become 1 of 10 sites under new Centers for Research in Emerging Infectious Diseases

Washington University School of Medicine in St. Louis is one of 10 sites and a coordinating center forming the Centers for Research in Emerging Infectious Diseases, funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH). The centers are a coordinated network with collaborators in different regions across the globe where emerging and re-emerging infectious disease outbreaks have proven likely to occur.

Researchers at Washington University School of Medicine in St. Louis are establishing a new international collaboration that aims to help scientists prepare for the next pandemic and, perhaps, provide insight into the current one.

The School of Medicine is one of 10 sites and a coordinating center forming the Centers for Research in Emerging Infectious Diseases, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Washington Universitys center will be supported by a five-year, $8.1 million grant.

The Centers for Research in Emerging Infectious Diseases (CREID) is a coordinated network with centers that will each have collaborators in different regions across the globe where emerging and re-emerging infectious disease outbreaks have proven likely to occur. The Washington University-led center includes researchers at La Jolla Institute for Immunology in San Diego and international collaborators in China, Hong Kong, Nepal and Ethiopia. In recent years, these regions have seen the emergence of multiple dangerous viruses, including H5N1 influenza, SARS, MERS and, most recently, SARS-CoV-2, the virus that causes COVID-19.

We want to be able to respond quickly and effectively to the emergence of a new infectious disease, said David Wang, PhD, principal investigator of the new center at Washington University. If we can understand the source of the infection, how it spreads and how it affects people, we have a better shot at preventing a new infectious disease from becoming a major threat to global public health.

Multidisciplinary teams of investigators will conduct surveillance of potential sources of new diseases and the local populations at risk of infection. The researchers will study transmission, disease progression, and immunologic responses in the host, and will develop diagnostic tests and animal models of the new diseases for improved detection of important emerging pathogens and the methods by which they spread.

Such information could help predict which new infectious diseases are at highest risk of reaching pandemic status and aid in efforts to understand the new disease and prevent its spread.

In addition to Wang, a professor of molecular microbiology, and of pathology & immunology, key researchers at Washington Universitys center include Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine; Jacco Boon, PhD, an associate professor of medicine; and Scott A. Handley, PhD, an associate professor of pathology & immunology.

The international centers will monitor local populations for the most common red flags of an emerging infection: respiratory disease, inflammation of the brain, and unexplained fever. The researchers will study patient samples to look for new viruses or other microbes with the potential to cause disease. At the same time, investigators will survey local livestock, mosquitoes and ticks to help identify the potential origins of viruses that could be infecting people in a particular region.

The Washington University researchers will focus on the molecular biology and genetics of emerging viruses and on developing animal models, such as mice and other rodents, to help study potentially dangerous viruses, understand how they spread and set the stage for developing treatments.

If we find a new virus that we want to prioritize, we will develop diagnostic tests, and tools to study the virus and will begin to develop treatments, such as therapeutic antibodies, Wang said. We could use our animal models to test possible new drugs. We also will fine tune plans so that we are quick to respond to new emerging outbreaks, such as SARS-CoV-2, first reported in Wuhan, China.

Weve prioritized studies of COVID-19 at the university, Wang added. Were sequencing the genomes of SARS-CoV-2 viruses to understand the transmission and evolution of the virus that is circulating in the St. Louis region. Were also trying to understand how the proteins that the virus makes contribute to the severity of the infection.

The new centers are prioritizing the study of families of viruses that have shown the most potential to impact humans, including coronaviruses (SARS-CoV and MERS-CoV), paramyxoviruses (measles and respiratory syncytial virus), flaviviruses (West Nile, Zika and dengue) and alphaviruses (chikungunya virus), among others.

There are clear sets of viral families that we are most concerned about because they have the highest likelihood of causing major disease in humans, Wang said. At the same time, were definitely looking for everything with our surveillance studies. Every viral family has the potential to be highly dangerous. We hope this program will help identify those infectious diseases most likely to cause major problems, so we can take steps to lessen the impact.

For more information, visit: https://creid-network.org

This work is supported by the NIAID of the NIH, grant number U01AI151810.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Identifying emerging diseases focus of new international collaboration - Washington University School of Medicine in St. Louis

Immunology

Asymptomatic COVID-19 Infections And ‘Disease Tolerance’ : Shots – Health News – NPR

'Disease tolerance' is the ability of an individual, due to a genetic predisposition or some aspect of behavior or lifestyle, to thrive despite being infected with an amount of pathogen that sickens others. It might play a role in asymptomatic coronavirus infections. Alexander Spatari/Getty Images hide caption

'Disease tolerance' is the ability of an individual, due to a genetic predisposition or some aspect of behavior or lifestyle, to thrive despite being infected with an amount of pathogen that sickens others. It might play a role in asymptomatic coronavirus infections.

One of the reasons Covid-19 has spread so swiftly around the globe is that for the first days after infection, people feel healthy. Instead of staying home in bed, they may be out and about, unknowingly passing the virus along. But in addition to these pre-symptomatic patients, the relentless silent spread of this pandemic is also facilitated by a more mysterious group of people: the so-called asymptomatics.

According to various estimates, between 20 and 45 percent of the people who get COVID-19 and possibly more, according to a recent study from the Centers for Disease Control and Prevention sail through a coronavirus infection without realizing they ever had it. No fever or chills. No loss of smell or taste. No breathing difficulties. They don't feel a thing.

Asymptomatic cases are not unique to COVID-19. They occur with the regular flu, and probably also featured in the 1918 pandemic, according to epidemiologist Neil Ferguson of Imperial College London. But scientists aren't sure why certain people weather COVID-19 unscathed. "That is a tremendous mystery at this point," says Donald Thea, an infectious disease expert at Boston University's School of Public Health.

The prevailing theory is that their immune systems fight off the virus so efficiently that they never get sick. But some scientists are confident that the immune system's aggressive response, the churning out of antibodies and other molecules to eliminate an infection, is only part of the story.

These experts are learning that the human body may not always wage an all-out war on viruses and other pathogens. It may also be capable of accommodating an infection, sometimes so seamlessly that no symptoms emerge. This phenomenon, known as disease tolerance, is well-known in plants but has only been documented in animals within the last 15 years.

Hints that 'disease tolerance' is at work

Disease tolerance is the ability of an individual, due to a genetic predisposition or some aspect of behavior or lifestyle, to thrive despite being infected with an amount of pathogen that sickens others. Tolerance takes different forms, depending on the infection. For example, when infected with cholera, which causes watery diarrhea that can quickly kill through dehydration, the body might mobilize mechanisms that maintain fluid and electrolyte balance. During other infections, the body might tweak metabolism or activate gut microbes whatever internal adjustment is needed to prevent or repair tissue damage or to make a germ less vicious.

"Why, if they have these abnormalities, are they healthy? Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study."

Janelle Ayres, physiologist, Salk Institute for Biological Studies

Researchers who study these processes rely on invasive experiments that cannot be done in people. Nevertheless, they view asymptomatic infections as evidence that disease tolerance occurs in humans. At least 90 percent of those infected with the tuberculosis bacterium don't get sick. The same is true for many of the 1.5 billion of people globally who live with parasitic worms called helminths in their intestines. "Despite the fact that these worms are very large organisms and they basically migrate through your tissues and cause damage, many people are asymptomatic. They don't even know they're infected," says Irah King, a professor of immunology at McGill University. "And so then the question becomes, what does the body do to tolerate these types of invasive infections?"

While scientists have observed the physiological processes that minimize tissue damage during infections in animals for decades, it's only more recently that they've begun to think about them in terms of disease tolerance. For example, King and colleagues have identified specific immune cells in mice that increase the resilience of blood vessels during a helminth infection, leading to less intestinal bleeding, even when the same number of worms are present.

"This has been demonstrated in plants, bacteria, other mammalian species," King says.

"Why would we think that humans would not have developed these types of mechanisms to promote and maintain our health in the face of infection?" he adds.

Maybe germs aren't the enemy: A more nuanced view

In a recent Frontiers in Immunology editorial, King and his McGill colleague Maziar Divangahi describe their long-term hopes for the field: A deeper understanding of disease tolerance, they write, could lead to "a new golden age of infectious disease research and discovery."

Scientists have traditionally viewed germs as the enemy, an approach that has generated invaluable antibiotics and vaccines. But more recently, researchers have come to understand that the human body is colonized by trillions of microbes that are essential to optimal health, and that the relationship between humans and germs is more nuanced.

Meddlesome viruses and bacteria have been around since life began, so it makes sense that animals evolved ways to manage as well as fight them. Attacking a pathogen can be effective, but it can also backfire. For one thing, infectious agents find ways to evade the immune system. Moreover, the immune response itself, if unchecked, can turn lethal, applying its destructive force to the body's own organs.

"With things like COVID, I think it's going to be very parallel to TB, where you have this Goldilocks situation," says Andrew Olive, an immunologist at Michigan State University, "where you need that perfect amount of inflammation to control the virus and not damage the lungs."

Some of the key disease tolerance mechanisms scientists have identified aim to keep inflammation within that narrow window. For example, immune cells called alveolar macrophages in the lung suppress inflammation once the threat posed by the pathogen diminishes.

Much is still unknown about why there is such a wide range of responses to COVID-19, from asymptomatic to mildly sick to out of commission for weeks at home to full-on organ failure. "It's very, very early days here," says Andrew Read, an infectious disease expert at Pennsylvania State University who helped identify disease tolerance in animals. Read believes disease tolerance may at least partially explain why some infected people have mild symptoms or none at all. This may be because they're better at scavenging toxic byproducts, he says, "or replenishing their lung tissues at faster rates, those sorts of things."

Asymptomatic COVID-19 infections

The mainstream scientific view of asymptomatics is that their immune systems are especially well-tuned. This could explain why children and young adults make up the majority of people without symptoms because the immune system naturally deteriorates with age. It's also possible that the immune systems of asymptomatics have been primed by a previous infection with a milder coronavirus, like those that cause the common cold.

Asymptomatic cases don't get much attention from medical researchers, in part because these people don't go to the doctor and thus are tough to track down. But Janelle Ayres, a physiologist and infectious disease expert at the Salk Institute For Biological Studies who has been a leader in disease tolerance research, studies precisely the mice that don't get sick.

The staple of this research is something called the "lethal dose 50" test, which consists of giving a group of mice enough pathogen to kill half. By comparing the mice that live with those that die, she pinpoints the specific aspects of their physiology that enable them to survive the infection. She has performed this experiment scores of times using a variety of pathogens. The goal is to figure out how to activate health-sustaining responses in all animals.

A hallmark of these experiments and something that surprised her at first is that the half that survive the lethal dose are perky. They are completely unruffled by the same quantity of pathogen that kills their counterparts. "I thought going into this ... that all would get sick, that half would live and half would die, but that isn't what I found," Ayres says. "I found that half got sick and died, and the other half never got sick and lived."

Ayres sees something similar happening in the COVID-19 pandemic. Like her mice, asymptomatic people infected with the novel coronavirus seem to have similar amounts of the virus in their bodies as the people who fall ill, yet for some reason they stay healthy. Studies show that their lungs often display damage on CT scans, yet they are not struggling for breath (though it remains to be seen whether they will fully escape long-term impacts). Moreover, a small recent study suggests that people who are asymptomatic mount a weaker immune response than those who get sick suggesting that mechanisms are at work that have nothing to do with fighting infection.

"Why, if they have these abnormalities, are they healthy?" asks Ayres. "Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study."

The goal of disease tolerance research is to decipher the mechanisms that keep infected people healthy and turn them into therapies that benefit everyone. "You want to have a drought-tolerant plant, for obvious reasons, so why wouldn't we want to have a virus-tolerant person?" Read asks.

A 2018 experiment in Ayres' lab offered proof of concept for that goal. The team gave a diarrhea-causing infection to mice in a lethal dose 50 trial, then compared tissue from the mice that died with those that survived, looking for differences. They discovered that the asymptomatic mice had utilized their iron stores to route extra glucose to the hungry bacteria, and that the pacified germs no longer posed a threat. The team subsequently turned this observation into a treatment. In further experiments, they administered iron supplements to the mice and all the animals survived, even when the pathogen dose was upped a thousandfold.

When the pandemic hit, Ayres was already studying mice with pneumonia and the signature malady of COVID-19, acute respiratory distress syndrome, which can be triggered by various infections. Her lab has identified markers that may inform candidate pathways to target for treatment. The next step is to compare people who progressed to severe stages of COVID-19 with those who are asymptomatic to see whether markers emerge that resemble the ones she's found in mice.

If a medicine is developed, it would work differently from anything that's currently on the market because it would be lung-specific, not disease-specific, and would ease respiratory distress regardless of which pathogen is responsible.

But intriguing as this prospect is, most experts caution that disease tolerance is a new field and tangible benefits are likely many years off. The work involves measuring not only symptoms but the levels of a pathogen in the body, which means killing an animal and searching all of its tissues. "You can't really do controlled biological experiments in humans," Olive says.

In addition, there are countless disease tolerance pathways. "Every time we figure one out, we find we have 10 more things we don't understand," King says. Things will differ with each disease, he adds, "so that becomes a bit overwhelming."

Nevertheless, a growing number of experts agree that disease tolerance research could have profound implications for treating infectious disease in the future. Microbiology and infectious disease research has "all been focused on the pathogen as an invader that has to be eliminated some way," says virologist Jeremy Luban of the University of Massachusetts Medical School. And as Ayres makes clear, he says, "what we really should be thinking about is how do we keep the person from getting sick."

Emily Laber-Warren directs the health and science reporting program at the Craig Newmark Graduate School of Journalism at CUNY.

This story was produced by Undark, a nonprofit, editorially independent digital magazine exploring the intersection of science and society.

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Asymptomatic COVID-19 Infections And 'Disease Tolerance' : Shots - Health News - NPR

Immunology

Ireland ranked best in the world for immunology research – Irish Post

IRELAND HAS been named the best country in the world for immunology sciences, giving morale a boost as the country's top scientists continue a search for a coronavirus vaccine.

The Science Foundation of Ireland yesterday confirmed that the Emerald Isle ranks first in the world for quality of science in immunology, thanks to a huge investment in science, technology, engineering and maths (STEM).

The SFI's report laid out Ireland's contribution to the science for 2019, with 2,894 international academic collaborations with 75 different countries, a 26% increase in education and public engagement activities, and 1,860 industry collaborations across Ireland being some of the highlights of the annual report.

Ireland also came close to topping the board a second time, being named 2nd in the world for its quality of agricultural sciences.

Minister for Further and Higher Education, Research, Innovation and Science, Simon Harris, welcomed the news yesterday as he launched the annual report.

He said:

The crucial role excellent research, international collaboration and innovative talent plays in helping us to respond to global challenges including Covid-19 has never been clearer, so today I am extremely pleased to launch SFIs 2019 Annual Report.

"Recent months have shown us the ability of Irelands research community to work together and deliver solutions for Ireland through SFI's Covid-19 Rapid Response Funding Call."

Chairman of the SFI, Professor Peter Clinch, said the outstanding achievements within the report "clearly demonstrate the crucial role that science and research play in our national effort to address the many societal and economic challenges we face."

Immunology and vaccine research has never been more important than in the year the Covid-19 pandemic shut down most of the world, which the Director General of the SFI and Chief Scientific Adviser to the Government of Ireland, Professor Mark Ferguson acknowledged at the launch of the report.

The Covid-19 pandemic has proven the critical importance of science and research in delivering solutions that support our future health, environment and quality of life," Prof Ferguson said.

"Our position as 1st in the world for quality of science in immunology means that Irish scientists are playing a crucial role in the global response to Covid-19.

"In addition to our expertise and impact in immunology, the Covid-19 Rapid Response Funding Call further demonstrates how SFI can respond quickly to work in collaboration with other funders and industry to support the best researchers across Ireland, embedding a culture of evidence-based policy and capitalising on the research capability in our Higher Education Institutions.

"For our society and economy, it is clear that research in science and innovation will play a critical role in our recovery; supporting development, attracting Foreign Direct Investment and harnessing transformational green technologies for a more sustainable Ireland.

The outstanding results come as the SFI invested a whopping 188 million from the Department of Business, Enterprise and Innovation in 2019.

According to the institution, the investment generated a further 223 million from the EU, Charity and other sources, and for every 1 invested by the State in SFI Research Centres, approximately 5 was returned to the economy.

You can read the Science Foundation Ireland annual report in full here.

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Ireland ranked best in the world for immunology research - Irish Post

Immunology

Immunology Trials and COVID-19 – An Overview of Changes to Clinical Practices and Clinical Trial Logistics in H1, 2020 as a Result of the Pandemic -…

Dublin, Aug. 28, 2020 (GLOBE NEWSWIRE) -- The "Coronavirus Disease 2019 (COVID-19) Impact on Immunology Trials - July 2020" report has been added to ResearchAndMarkets.com's offering.

Since the beginning of March 2020, clinical trial operations were most disrupted as a result of the COVID-19 pandemic. This report summarizes the impact on immunology patient, clinical trial logistics, and key opinion leader (KOL) insights on the long-term impact of the pandemic.

Report Scope

Reasons to Buy

Key Topics Covered

1 Immunology Trials Disrupted1.1 Overview of Immunology Trials Disrupted1.2 Regulatory Guidance Across the 8MM

2 KOL Insights: Continuity of Care

3 KOL Insights: Trial Logistics3.1 Recruitment3.2 Conduct in Isolation3.3 Supply Chain

4 KOL Insights: Trials Looking Forward4.1 Clinical Trials Disrupted Due to COVID4.2 Immunology Clinical Trials Resumed

5 Appendix

For more information about this report visit https://www.researchandmarkets.com/r/5kx76f

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Immunology Trials and COVID-19 - An Overview of Changes to Clinical Practices and Clinical Trial Logistics in H1, 2020 as a Result of the Pandemic -...

Immunology

STING is a hot target in immunology research and drug discovery – BioWorld Online

Detailed research over the past decade has shown that that the protein stimulator of interferon genes (STING) is a master regulator of type I interferons and as such plays an essential role in activating innate immunity. When the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) detects double-stranded DNA in the cytosol, from either an infectious pathogen or a damaged nucleus, an immune response is initiated downstream by STING that eventually leads to the activation of T cells. STINGs importance in orchestrating the bodys response to pathogenic, tumor, or self-DNA in the cytoplasm has made it a hot target in immunology research and drug discovery, and several biopharma companies have started programs dedicated to this area spanning infectious and inflammatory diseases as well as cancer.

The potential of STING to enhance antitumor immunity through the induction of a variety of pro-inflammatory cytokines and chemokines, including type I interferons, is a relatively new line of inquiry that is creating considerable excitement, although much of the research on new therapies remains at the early clinical stages.

Aduro Biotech Inc., of Berkeley, Calif., which is focused on developing therapies targeting the immune system cGAS-STING and APRIL (A Proliferation-Inducing Ligand) pathways to treat cancer, autoimmune and inflammatory diseases, in its second quarter financial results reported that they are enrolling patients in a phase II study of ADU-S100 in combination with pembrolizumab in squamous cell carcinoma of the head and neck and are progressing their cGAS-STING antagonist research collaboration with Eli Lilly and Co.

As part of a December 2018 agreement, Lilly gained access to molecules from Aduro that are designed to inhibit the cGAS-STING pathway. The companies are collaborating to advance these molecules, as well as others from Lilly, into clinical development. Aduro received an up-front payment of $12 million and is eligible for development and commercial milestones up to approximately $620 million per product, as well as royalty payments in the single to low-double digits should Lilly successfully commercialize a therapy from the collaboration.

In business development, Aduro is merging with privately held Chinook Therapeutics Inc. and, going forward, Stephen Isaacs, chairman, president and CEO of the company noted, We ended the second quarter of 2020 with a cash position of $186.1 million, which we believe will enable us to continue our ongoing STING and APRIL programs in the near-term and also meet our net cash requirements at the close of the merger with Chinook.

Hopkinton, Mass.-based Spring Bank Pharmaceuticals, Inc. also is developing a STING product portfolio with its lead clinical product candidate, SB 11285, an intravenously-administered immunotherapeutic agent for the treatment of selected cancers, as well as STING antagonist compounds for the treatment of a broad range of inflammatory diseases, and a STING agonist ADC program for potential oncology applications. It is collaborating with Roche Holding AG to co-administer SB-11285 with the pharmas PD-L1 checkpoint inhibitor, atezolizumab (Tecentriq), in patients with advanced solid tumors.

After the company stopped phase II studies of inarigivir soproxil 400 mg to treat chronic hepatitis B virus in December 2019, Martin Driscoll, president and CEO explained that they undertook an extensive review of strategic options that finally led to a proposed combination with F-star Therapeutics Ltd.

The combined company, operating under the name F-star Therapeutics, Inc., will advance an immuno-oncology pipeline of multiple tetravalent bispecific antibody programs, as well as SB-11285, which the F-star leadership team has committed to continuing the ongoing clinical trial, Driscoll added.

AbbVie Inc. took a position in the field last year when it acquired Seattle-based Mavupharma Inc., whose lead clinical candidate is MAVU-104, a first-in-class, orally active, small-molecule inhibitor of ENPP1, an enzyme involved in the regulation of the STING pathway. Inhibiting ENPP1 activity with MAVU-104 allows for highly controlled enhancement of STING signaling in tumors without the need for injections, Abbvie explained.

Collaborative research

Last year, Novartis AG also gained a foothold in the STING space investing in Boston-based IFM Therapeutics LLC. agreeing to pay IFM shareholders up to $840 million for an exclusive option to acquire a subsidiary they launched to develop new drugs for the treatment of inflammatory and autoimmune diseases, IFM Due Inc.

Lead optimization for the programs a suite of cGAS (cGMP-AMP synthase) inhibitors and STING (stimulator of interferon genes) antagonists is underway, with trials of the first STING antagonist expected to begin in 2021.

This wasnt the first foray into STING R&D for Novartis. However, its collaboration with Aduros STING pathway activator ADU-S100 did not generate impressive results and it eventually dropped a phase Ib study of the compound in combination with its own anti-PD-1 monoclonal antibody spartalizumab in advanced, metastatic treatment-refractory solid tumors.

In March, Berlin, Germany-based Bayer entered a research collaboration and license agreement for Curadev Pvt. Ltd.s STING antagonist program that aims to discover new drug candidates to treat lung, cardiovascular and other inflammatory diseases. The companies will work to optimize and advance these molecules, as well as others generated during the collaboration, into clinical development.

This was the second big pharma deal for Curadev. Last year it licensed its STING agonist (CRD-5500) and associated patents to Takeda Pharmaceutical Co. Ltd.

Editors note: Part two of this feature will examine the most recent STING research and clinical pipeline as well as the venture capital now flowing into the field.

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STING is a hot target in immunology research and drug discovery - BioWorld Online

Immunology

With Key Data Nearing, Tonix Looks to Spotlight Robust Pipeline In Immunology And CNS Therapeutics – Yahoo Finance

The following article is sponsored by the clinical communications unit of Redington, Inc. The information contained in this article in no way represents investment advice or opinion on the part of Benzinga or its writers and is intended for informational purposes only.

Tonix Pharmaceuticals Holding Corp. (NASDAQ: TNXP) has been operating under the radar of major institutional investors, but that may soon change.

After a series of near misses in a handful of clinical trial programs, the company is closing in on data from two important programs. Positive readouts from either one promises to spotlight the companys diverse portfolio built on unmet needs in billion-dollar medical categories.

Before yearend, Tonix expects to release data from advanced non-human primate studies of its lead Covid-19 T cell eliciting vaccine candidate utilizing live attenuated virus vectors. Vaccines made with attenuated viruses are known to confer long term immunity with a single dose (think vaccines for smallpox, measles, mumps and rubella) and they are the only ones known to prevent forward transmission or contagion.

Tonixs decision to develop T cell vs. antibody eliciting vaccines puts it in a race alongside Merck & Co. (NYSE: MRK), the only other US company developing Covid-19 vaccines with a similar approach.

Another expected fourth quarter highlight could position Tonix to tap into a nearly $9 billion fibromyalgia drug market, one that was created by Pfizer, Incs (NYSE: PFE) Lyrica and Eli Lilly and Companys (NYSE: LLY) Cymbalta before both products went generic two years ago.

Tonixs fibromyalgia candidate, TNX-102 SL, is more than half-way through a Phase 3 registration trial, with topline results due before yearend.

No new branded fibromyalgia drug has entered the market since Cymbalta and Lyrica went generic a void Tonix hopes to fill with a better, more tolerable product following completion of its Phase 3 programs.

We are nimble, focused and we work on big medical challenges, said Tonix CEO Seth Lederman, MD in a recent interview with Benzinga. Many other companies are focused on a particular proprietary technology, while we are opportunity-focused.

Driven By Opportunity

In describing the driving philosophy underlying Tonix Pharmaceuticals trials of its leading and exploratory drug candidates, Dr. Lederman emphasized the companys focus on discovering impactful approaches to often overlooked clinical diagnoses.

This is particularly reflected in Tonixs pursuit of a non-addictive treatment for fibromyalgia, a generalized pain disorder that is often misdiagnosed or mistreated due to the multifarious manifestations of the condition.

We like the opportunity-focused model better because it fits more directly with our passion for tackling medical problems that others avoid because of past failures or other difficulties, Dr. Lederman elaborated. We believe we can win some victories for desperate patients that medicine has heretofore overlooked because the hill seemed too steep to climb. The solutions we seek have the potential to be tremendously meaningful and rewarding

In this interview, Dr. Lederman spoke to the history and progress of both drug candidates as well as the unique markets they aim to serve. He also touches on his personal history in rheumatology, patient pain-management and immunology and what the future looks like for Tonixs lead drug candidates and for the company.

The companys strategy often involves looking at markets that have been created by blockbuster products, identifying their shortcomings, and then developing novel approaches to deliver a unique product profile.

One of the big triumphs of rheumatology was the recognition some 15 years ago that fibromyalgia was a distinct disorder, not a stigmatized set of complaints offered up by folks who doctors thought were malingerers with fabricated symptoms, Dr. Lederman explained.

That victory has led to other advances, for example, the understanding that fibromyalgia is a chronic pain disorder relating to central pain.

As the formal diagnoses of fibromyalgia were being advanced, Pfizer launched Lyrica and Lilly launched Cymbalta, which had combined peak sales of roughly $9 billion before they went off patent. Now there is only one remaining branded product on the market Savella from AbbVie Inc. (NYSE: ABBV) a Cymbalta-like drug selling at the rate of about $400 million a year.

Story continues

At peak sales, Cymbalta was a $5 billion product and Lyrica wasnt far behind at $3.5 billion, Dr. Ledrman elaborated. Now that both are generic, the dollar value of the market is smaller, but the patients havent disappeared in fact, if anything, theyve grown in number and there is still widespread dissatisfaction within their ranks. Our research indicates that doctors and patients are constantly on the search for other options. We think we can capitalize on that dissatisfaction with a substantially differentiated product.

For Dr. Lederman, the pursuit is more than simply one of opportunity. He has a longstanding interest in the diagnosis of fibromyalgia dating back to his medical training with Columbia Universitys Division of Rheumatology 35 years ago.

It is all about knowing the cause and source of the pain, he said.

Dr. Lederman explained that, as opposed to nociceptive and neuropathic, which denote pain caused by injury to the body or parts of the central nervous system, central pain originates in an individuals brain. This distinction, as well as advances in patient care, helped to foster the recognition of fibromyalgia as a distinct medical condition affecting about seven million adults in the United States, with 95% of those being female over the age of 50 who generally begin experiencing symptoms with the onset of menopause.

With the introduction of FDA-approved Cymbalta and Lyrica and later a drug called Savella doctors moved many patients away from off-label treatments, but dissatisfaction still runs high with a lot of switching and on-off use, often due to side effects becoming intolerable.

As a result, there is still widespread use of addictive opiates. Although they are not approved for this indication, Dr. Lederman asserts that one-third of fibromyalgia patients end up on long-term opiates. These patients often end up in a very bad place and become part of the rising death toll attributed to opiate overdose.

We believe TNX-102 SL will provide a meaningful alternative, a better option.

Seeking Solutions To A Painful Syndrome

The current Phase 3 trial of TNX-102 SL in fibromyalgia was initiated last year following a prior, lower-dose trial that fell short of endpoint results.

TNX-102 SL aims to distinguish itself from existing fibromyalgia treatments by acting on a patients central nervous system to inhibit symptoms of pain by improving sleep quality, which Dr. Lederman sees as a key feature in addressing one of the most consistent aspects of the overall condition.

Fibromyalgia is a syndrome that is defined by a collection of symptoms, he explained. By addressing this sleep disturbance symptom with TNX-102 SL, we've shown in two large studies that there was improvement in fibromyalgia that extends beyond sleep and into improvement across the spectrum of other fibromyalgia symptoms. Because TNX-102 SL provides improvement of many different symptoms, beyond the sleep quality improvement, we believe that TNX-102 SL acts at a syndrome-level and not just at the symptom-level.

Dr. Lederman sees the opportunity in TNX-102 SL as an alternative for patients who might suffer deleterious side effects that impact the quality of the treatment or cause patients to stop taking them altogether.

TNX-102 SL is a medicine taken every night at bedtime, and it has been well-tolerated in all the studies we've done, although some patients experience side effects like transient numbness in the mouth, sleepiness and dry mouth explained Dr. Lederman. Based on the two prior studies and our experience with the 5.6 mg dose in PTSD, we believe TNX-102 SL could have a tolerability edge.

While the peaks sales numbers for Cymbalta and Lyrica may seem lofty, Dr. Lederman is encouraged by the numbers and the need they demonstrate for an array of fibromyalgia treatment options. Tonix is also exploring other potential indications for TNX-102 SL, including for symptoms associated with alcoholism and Alzheimers disease.

This is an exciting time for our portfolio of 10 CNS indications, and especially for TNX-102 SL in fibromyalgia. We look forward to an interim analysis in the Phase 3 study to be reported next month, and we expect top line data from that study in the fourth quarter of this year.

Live Vaccines in An Ongoing Pandemic

In addition to progress on the TNX-102 SL trials, Dr. Lederman also touched on the other leading drug candidates that Tonix is currently putting resources toward investigating, several self-attenuated vaccines for the COVID-19 virus strain. The pursuit is especially dire in Dr. Ledermans estimation, characterizing the ongoing pandemic as the biggest global public health threat since the Spanish Flu in 1918.

We have several vaccine candidates in development, all based on our proprietary live attenuated-virus vector platform, said Dr. Lederman. Live attenuated viruses like horsepox or bovine parainfluenza virus can induce infected lung cells to present antigens to T cells directly. TNX-1800, our lead vaccine in development, is designed to express the spike protein from CoV-2, the virus that causes Covid-19.

The interest in developing a novel and effective vaccine should be self-evident to most given the mounting infection rates. And while many of the potential early vaccine candidates from firms like Moderna, Inc. (NASDAQ: MRNA) or AstraZeneca PLC (NYSE: AZN) have progressed into trial stages, Dr. Lederman highlighted the need for a variety of vaccine platforms. This is in order to both find an ideal vaccine for the virus as well as a greater variety of effective vaccines that can be used in case others are ineffective in certain individuals.

There are currently over 150 potential Covid-19 vaccines in various stages of development but relatively few utilize live attenuated viral platforms. Live attenuated viruses have the potential to confer long-term immunity and prevent forward transmission, Dr. Lederman said. These vaccines are live, attenuated vaccines, like the vaccines that successfully eradicated smallpox, and helped to contain rubella, mumps, measles, and several other lethal viruses.

In a practical sense, Dr. Lederman explained that the ability to prevent forward-transmission the spread of the virus from one host to another is what sets live-attenuated vaccines apart from vaccines derived from inactivated virus strains. The active stimulation of the immune systems Tcells that result from effective live-attenuated vaccines is what evokes a strong, long-lasting and durable immunity to the virus strain.

The challenge of developing such a vaccine lies in working with similar viral strains as a platform and, even then, no one vaccine is 100% effective in all cases. This is another area of opportunistic research on the part of Tonix, which recently announced a sponsorship with Columbia University that Dr. Lederman explained is meant to address these potential variables and to develop precision medicine tools that would allow tailoring of vaccines based on a persons biomarkers.

At the moment, Tonix is still exploring the potential of the horsepox and BPI virus platforms, with the former producing one of the companys more viable vaccine candidates, TNX-1800, which is in pre-IND phase of development.

Should the animal studies prove positive, the company expects to start human trials of TNX-1800 next year.

Said Dr. Lederman, We recently announced a partnership with Fujifilm Diosynth in College Station, Texas, who will be manufacturing the vaccine. We expect it will be manufactured at the level of quality and in a sufficient quantity to conduct clinical trials next year. We are also guiding that we will have the results of both small animal and non-human primate studies in the fourth quarter of this year. Those results will include studies of non-human primates that were challenged with the CoV-2 virus.

Drawing the interview to a close, Dr. Lederman reflected that, between the phase 3 fibromyalgia treatment and the ongoing exploration of a COVID-19 vaccine, Tonix Pharmaceuticals is focused on exactly the specialized and targeted drug development that has guided its mission thus far.

We are well-funded at the moment with $67 million pro forma cash on hand at June 30 and all in all, we think this is a very exciting time for Tonix he said.

See more from Benzinga

2020 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

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With Key Data Nearing, Tonix Looks to Spotlight Robust Pipeline In Immunology And CNS Therapeutics - Yahoo Finance

Immunology

Global Immunology Market 2020 Research Report with COVID-19 Impact, by Future Trend, Growth rate and Industry Analysis to 2025 – Good Night, Good…

An up-to-date intelligence study by Global Immunology Market 2020 by Company, Regions, Type and Application, Forecast to 2025 provides the present scenario of the market and offers a comparative assessment of the market. The report provides historical data, significance, statistical data, size & share, market price & demand, business overview, market analysis by product and market trends by key players. It detects that the global Immunology market by technological advancements and the presence of a large number of players, who are making the competitive landscape distributed. The report further highlights current growth factors, market threats, attentive opinions, and competitive analysis of major Immunology market players, value chain analysis, and future roadmap.

Competitiveness:

The Immunology market is fragmented and is characterized by the presence of key vendors and other prominent vendors. Key vendors are trying to maintain themselves in the global Immunology market, whereas, regional vendors are focusing on product offerings to establish themselves in the market. Vendors are providing a different range of product lines intensifying the competitive scenario.

NOTE: Our report highlights the major issues and hazards that companies might come across due to the unprecedented outbreak of COVID-19.

DOWNLOAD FREE SAMPLE REPORT: https://www.researchstore.biz/sample-request/11508

Market Potential:

The market vendors have been forecasted to obtain new opportunities as there has been an increased emphasis on spending more on the work of research and development by many of the manufacturing companies. Additionally, many of the market participants are anticipated to make a foray into the emerging economies that are yet to be explored so as to find new opportunities. The global Immunology market has gone through rapid business transformation by good customer relationships, drastic and competitive growth, significant changes within the market, and technological advancement in the worldwide market.

Topmost list manufacturers/ key player/ economy by business leaders leading players of the market are: AbbVie, eFFECTOR Therapeutics, Johnson& Johnson, Amgen, Cellectar Biosciences, F. Hoffmann-La Roche, Celgene, Bionor Pharma

Geographically, this report studies market share and growth opportunity in the following key regions: North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India, Southeast Asia and Australia), South America (Brazil, Argentina, Colombia), Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)

On the basis of product segment, this report covers: Immuno Boosters, Immunosuppressants,

On the basis of Application segment, this report covers: Autoimmune Diseases, Oncology, Organ Transplantation, Others,

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Important Take-Away:

Moreover, the report has covered the PEST analysis by region and key economies across the globe, PORTERs analysis, and detailed SWOT analysis of key players to analyze their strategies. It guides companies to make effective business strategy decisions by knowing the global Immunology market conditions and sentiment within the market. The report serves to adjust investment allocation by outlining key focus areas of the industry.

Customization of the Report:This report can be customized to meet the clients requirements. Please connect with our sales team (sales@researchstore.biz), who will ensure that you get a report that suits your needs. You can also get in touch with our executives on +1-201-465-4211 to share your research requirements.

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Researchstore.biz is a fully dedicated global market research agency providing thorough quantitative and qualitative analysis of extensive market research.Our corporate is identified by recognition and enthusiasm for what it offers, which unites its staff across the world.We are desired market researchers proving a reliable source of extensive market analysis on which readers can rely on. Our research team consist of some of the best market researchers, sector and analysis executives in the nation, because of which Researchstore.biz is considered as one of the most vigorous market research enterprises. Researchstore.biz finds perfect solutions according to the requirements of research with considerations of content and methods. Unique and out of the box technologies, techniques and solutions are implemented all through the research reports.

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Immunology

The American Academy of Allergy, Asthma & Immunology and National Association of School Nurses Release Guidance on School Attendance, Asthma and…

New document summarizes the current overall recommendations for treating students with asthma at school during the ongoing pandemic.

MILWAUKEE, Wis. (PRWEB) August 27, 2020

The American Academy of Allergy, Asthma & Immunology (AAAAI) and National Association of School Nurses (NASN) have released School Attendance, Asthma and COVID-19, a document that contains considerations for school nurses as schools begin to re-open amid the COVID-19 pandemic.

While certain evaluation procedures and treatment recommendations for students with asthma are no longer consistent due to the COVID-19 pandemic and a lack of objective data to guide recommendations, this new document aims to summarize overall recommendations that may be updated as more data surrounding COVID-19 becomes available.

The document addresses considerations when it comes to personal protective equipment (PPE), daily controller medications, and treatment for asthma prior to physical activity. It also touches on asthma action plans and guidance regarding distinguishing symptoms of COVID-19 from asthma. A case scenario is also included to provide school nurses with a concrete example of what procedures should be followed if an asthmatic student reports to them with symptoms of cough or shortness of breath.

Robert F. Lemanske Jr., MD, FAAAAI, a past AAAAI President and Chair of the AAAAI Office of School-based Management of Asthma who helped create the document, expressed why he felt this resource was so important for the AAAAI and NASN to put together. "School nurses are facing a challenging year, particularly for managing conditions such as asthma that may present similar symptoms to COVID-19. While there are no national recommendations, the AAAAI and NASN hope this document can act as a resource to protect school nurses, staff and of course, students while still providing optimal asthma care."

Donna Mazyck, NASN Executive Director, shared the importance for school nurses to have evidence-based considerations for managing asthma in students with asthma while in school buildings during COVID-19. "Asthma is a common chronic illness in students. A science-based approach to guide school nurse practice improves the health and wellbeing of students with asthma."

The AAAAI and NASN previously worked together on the AAAAI's School-based Asthma Management Program (SAMPRO), which details the elements necessary for the education of children, families, clinicians, and school-based personnel based on a "circle of support" that enhances multidirectional communication and promotes better care for children with asthma within the school setting. Further information on SAMPRO, which is endorsed by the NASN and others, can be found here.

You can also learn more about asthma and COVID-19 on the American Academy of Allergy, Asthma & Immunology website, aaaai.org.

About AAAAI

The American Academy of Allergy, Asthma & Immunology (AAAAI) represents allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic and immunologic diseases. Established in 1943, the AAAAI has more than 7,100 members in the United States, Canada and 72 other countries. The AAAAI's Find an Allergist/Immunologist service is a trusted resource to help you find a specialist close to home.

About NASN

The National Association of School Nurses is a non-profit specialty nursing organization, first organized in 1968 and incorporated in 1977, representing school nurses exclusively. NASN has more than 17,000 members and 50 affiliates, including the District of Columbia and overseas school nurses. The mission of NASN is to optimize student health and learning by advancing the practice of school nursing. Please visit us at http://www.nasn.org.

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Immunology

Scientists Think They’ve Figured Out a Main Culprit of Inflammatory Bowel Disease – ScienceAlert

Between 6 and 8 million people worldwide suffer from inflammatory bowel disease, a group of chronic intestinal disorders that can cause belly pain, urgent and frequent bowel movements, bloody stools and weight loss.

New research suggests that a malfunctioning member of the patient's own immune system called a killer T cell may be one of the culprits. This discovery may provide a new target for IBD medicines.

The two main types of IBD are ulcerative colitis, which mainly affects the colon, and Crohn's disease, which can affect the entire digestive tract. Researchers currently believe that IBD is triggered when an overactive immune system attacks harmless bacteria in the intestines.

Although there are many treatments for IBD, for as many as 75 percent of individuals with IBD there are no effective long-term treatments. This leaves many patients without good options.

I am a physician-scientist conducting research in immunology and IBD and in a new study, my team and our colleagues specializing in immunology, gastroenterology and genomics examined immune cells from the blood and intestines of healthy individuals and compared them with those collected from patients with ulcerative colitis to gain a better understanding of how the immune system malfunctions in IBD.

There are many reasons why current treatments aren't permanent, but one reason is that scientists don't fully understand how the immune system is involved in IBD. It is our hope that closing the current knowledge gap about how the immune system is involved in this disorder will eventually lead to new durable treatments for IBD that target the right immune cells.

The immune system can be divided into innate and adaptive branches. The innate branch is our first line of defense and acts quickly within minutes to hours. But this system senses changes caused by microbes generally. It does not mount a targeted response against a specific pathogen, which means that some invaders can be overlooked.

The adaptive branch is designed to detect specific threats, but is slower and takes a couple of days to get going. T cells are a part of the adaptive immune system and can be further subdivided into CD4 and CD8 T cells.

CD4 T cells are helpers that aid other immune cells by releasing soluble molecules called cytokines that can induce inflammation.

CD8 T cells can also release cytokines, but their main function is to kill cells infected by microbial invaders. This is why CD8 T cells are often referred to as serial killers.

After the infection is cleared and the pathogen has been destroyed, cells called memory T cells remain. These memory T cells "remember" the pathogen they've just encountered and if they see it again, they mount a stronger and faster response than the first time. They and their descendants can also live for a long time, even decades in the case of certain infections like measles.

The goal of a vaccine is to provide a preview of the microbe so that the immune system can build an army of memory cells against an infectious agent, such as SARS-CoV-2, the virus that causes COVID-19. That way, if the virus attacks, the memory T cells will spring into action and activate an immune response including the production of antibodies from B cells.

Immunologists further subdivide memory T cells into different classes depending on if and where they travel in the body. Circulating memory T cells are scouts that look for signs of infection by patrolling the blood, lymph nodes and spleen.

Tissue-resident memory cells, abbreviated TRM, are sentries stationed at key ports of entry into the human body including the skin, lungs, and intestines and act rapidly to counter an infectious threat. Intestinal TRM also function as peacekeepers and do not tend to overreact against the many harmless microbes living in the intestines.

In the new study, our team analyzed blood and intestinal samples to discover that intestinal CD8 TRM come in at least four different varieties, each with unique features and functions.

We noticed that individuals with ulcerative colitis had higher numbers and proportions of cells belonging to one of these four varieties. This particular variety, which we'll call inflammatory TRM here, carried instructions to make very large amounts of cytokines and other protein factors that allow them to kill other cells. High levels of certain cytokines can cause inflammation and tissue damage in the body.

It seems that in individuals with ulcerative colitis, the balance of memory cells is shifted in favor of this rogue population of inflammatory TRM that may become part of the problem by causing persistent inflammation and tissue damage.

We also found evidence consistent with the possibility that these inflammatory TRM might be exiting the intestinal tissue and entering the blood. Other studies in mice and people have shown that TRM, despite being called "tissue-resident," can leave tissues in certain circumstances.

By leaving the tissue and entering the blood, inflammatory TRM may be able to travel to other parts of the body and cause damage. This possibility may explain why autoimmune diseases that start in one organ, like IBD in the digestive tract or psoriasis in the skin, often affect other parts of the body.

The very features that make memory T cells so desirable for vaccines their capacity to live for such a long time and mount a stronger response when they encounter a microbial invader for the second time may explain why autoimmune diseases are chronic and lifelong.

It is important to point out that none of the current drug treatments for IBD specifically target long-lived memory cells, which might be a reason why these therapies don't work long-term in many individuals. One therapeutic approach might be to target inflammatory TRM for destruction, but this could result in side effects like suppression of the immune system and increased infections.

Our findings build on previous studies showing that different TRM varieties, like the CD4 subtype, may also be involved in IBD, while other studies show that TRM play a role in autoimmune diseases affecting other organs like the skin and kidneys.

The possibility that T cell memory is co-opted in IBD is exciting, but there is much that we still don't understand about TRM.

Can we selectively target inflammatory TRM for destruction? Would this be an effective treatment for IBD? Can we do so without causing major side effects? Further research will be needed to answer these important questions and to strengthen the link between TRM and IBD.

John Chang, Professor of Medicine, University of California San Diego.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Immunology

Video: COVID-19 Why it Matters Video Series Introduction with Brian Merkel – UWGB

This video series features UW-Green Bays Immunologist Brian Merkel on COVID-19 and Why it Matters. This series empowers viewers with knowledge to help them navigate through the pandemic. Merkel has a Ph.D. in Microbiology & Immunology from the Medical College of Virginia. He is an associate professor in UW-Green Bays Human Biology & Biology programs and has an appointment at the Medical College of Wisconsin Department of Microbiology and Immunology. He will be responding to a number of questions related to COVID19 and try to get behind the why its important to be educated in your decision-making as we navigate the pandemic together.

Video Transcript Series Introduction with Brian Merkel:

Brian Merkel, Microbiology and Immunology, I have a Ph.D. from the Department of Microbiology and Immunology from the Medical College of Virginia. I currently have an appointment in the Microbiology Department and Immunology Department for the Medical College of Wisconsin, and I am the incoming chair of Human Biology at the University of Wisconsin Green Bay. And so today we are going to talk about why COVID-19 matters to you. So, the goal of these discussions is to empower you and to help you understand why this disease affects everyone and what you can do about it. So, over the series of several videos that will be our goal to do just that.

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Video: COVID-19 Why it Matters Video Series Introduction with Brian Merkel - UWGB