Category Archives: Immunology

Oxford Immunotec Announces Donation in Support of Coronavirus Testing Efforts to Help Differentiate Tuberculosis from the New China Virus – BioSpace

January 23, 2020 medical

OXFORD, United Kingdom and MARLBOROUGH, Mass., Jan. 23, 2020 (GLOBE NEWSWIRE) -- Oxford Immunotec Global PLC (Nasdaq:OXFD) (the Company), a global, high-growth diagnostics company, today announced they are planning a new initiative to commemorate the coming World Tuberculosis Day, bring the benefits of the T-SPOT.TB test to mainland China and assist with differentiating tuberculosis (TB) from other respiratory infections. Oxford Immunotec will donate tests approximately valued at CNY 3,000,000 to Chinese hospitals through a non-profit organization, Bethune Charitable Foundation, in support of their efforts to combat the outbreak of the coronavirus.

Because some pathogens present with similar symptoms as TB, ruling out TB quickly in infected suspects is critical to fighting the spread of the infection. Since its approval in the Peoples Republic of China in 2010, T-SPOT.TB has been recognized for its high level of sensitivity and specificity across patient populations and has become a critical aid in the diagnosis of TB infection.

The donation plan is supported by leading hospitals and KOLs in China. Prof. Mou Xiangdong, Director of Respiratory and Critical Care Department, Beijing Tsinghua Chang Gung Hospital says, We would like to thank Oxford Immunotec for their commitment to the Chinese people. As symptoms of some infections may be similar to TB, this test will help us differentiate these illnesses with greater accuracy during epidemic seasons.

About T-SPOT.TB

The T-SPOT.TB test is available in over 60 countries and recognized by the World Health Organization (WHO) as one the 100 essential diagnostic tests that should be available in every country. In China, the T-SPOT.TB test has been on the market since 2010 and has been rapidly adopted by the leading hospitals and physicians as a critical tool for diagnosing TB infection. Today more than 250 of Chinas top hospitals rely on the T-SPOT.TB test to determine treatment for hard to diagnose patients. There is no comparable technology with similar sensitivity and specificity on the market in China. The T-SPOT.TB test is relied on as an essential tool in the fight against TB.

About Oxford Immunotec

Oxford Immunotec Global PLC is a global, high-growth diagnostics company focused on developing and commercializing proprietary assays for immunology and infectious disease. The Companys T-SPOT.TB test has been approved for sale in over 60 countries, including the United States, where it has received pre-market approval from the Food and Drug Administration, Europe, where it has obtained a CE mark, as well as Japan and China. The Company is headquartered near Oxford, U.K. and in Marlborough, MA. Additional information can be found at http://www.oxfordimmunotec.com.

CONTACTS:

For Media and Investor Inquiries: Matt McLaughlinChief Financial OfficerOxford ImmunotecTel: +1 (508) 573-9953mtmclaughlin@oxfordimmunotec.com

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Oxford Immunotec Announces Donation in Support of Coronavirus Testing Efforts to Help Differentiate Tuberculosis from the New China Virus - BioSpace

Immunology

L2P Research (Former AJES Life Sciences, LLC) and Transcell Oncologics, LLC Announce Partnership to Provide High Quality Hu-CB-CD34 and Hu-PBMC to…

January 23, 2020 medical

ANNVILLE, Pa.--(BUSINESS WIRE)--L2P Research, LLC and Transcell Oncologics, LLC have entered into a partnership with the purpose of marketing and the distribution of Transcell Oncologics, LLC Trans HSC (CD34+), Trans-HSC (PBMC) product line and L2P Researchs humanized mouse models.

L2P Research, LLC is a Pennsylvania based Research organization founded with a vision to provide integrated R&D support in all the key areas of Pharmaceutical development. L2P provides a complete array of research services as required for Investigational New Drug Applications (IND). Transcell Oncologicss Transtoxbio portfolio (www.transtoxbio.com) is all about human sourced primary progenitor cell based predictive platforms that work for exploratory drug and cosmetics research meant for clinics.

The agreed terms of this partnership highlight the product line dealing with CD34+ cells and Humanized mouse models, the scope of joint business development utilizes both companys capabilities jointly to address demand, quality, fit with preclinical research grade stem cells ( For Academia, Pharma, Contract Research Organizations) in the USA.

CAT# TRANS-HSC-CBM; CAT#TRANS-HSC-CBCD34; CAT#TRANS-HSC-PBCD34Represent the CD34+ cells available lots.

CAT#TRANS-HSC-HMRepresent the humanized mouse models available to the user.

CD34+ cells and the cell based humanized animal models market is projected to reach $ 200 M by 2022 with their applications shown in Oncology, Immunology, Infectious Diseases, Neuroscience, Toxicology, and Hematopoiesis by the user.

This specific partnership between Transcell Oncologics and L2P Research is confident to address the existing gap seen between the demand and the quality of supply owing to respective groups advantageous positions and credibility dealing with right kind of cells and the animal models.

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L2P Research (Former AJES Life Sciences, LLC) and Transcell Oncologics, LLC Announce Partnership to Provide High Quality Hu-CB-CD34 and Hu-PBMC to...

Immunology

New Investments Expected To Boost The Z-drugs Market Between ‘ 2019’ And ‘2027’ Dagoretti News – Dagoretti News

January 23, 2020 medical

Global Z-drugs Market Introduction

Nonbenzodiazepines, commonly referred as Z-drugs, are a widely prescribed class of psychoactive drugs for the treatment of different types of sleep disorders, particularly insomnia, which affects millions of people across the world. These drugs have similar effects as benzodiazepines by potentiating GABA (gamma-aminobutyric acid) activity in the body.

Global Z-drugs Market Competitive Landscape

Teva Pharmaceutical Industries Ltd., Sanofi, and Pfizer, Inc. are the major players operating in the global Z-drugs market. New product development and focus on emerging markets where the prevalence of insomnia is high are the strategies adopted by these players to increase market share.

Report Overview @https://www.transparencymarketresearch.com/z-drugs-market.html

Teva Pharmaceutical Industries, Ltd.

Teva Pharmaceutical Industries Ltd. is a key manufacturer of generic medicines and a recognized leader in innovative and specialty pharmaceuticals across the globe. The company delivers high quality and patient-centric health care solutions. It has a broad generics portfolio, with more than 1,000 molecules in nearly every therapeutic area. It continues to evaluate opportunities for joint ventures, collaborations, and other activities that support growth. Teva Pharmaceutical Industries focuses on establishing leadership position in its core therapeutic areas of respiratory (including asthma & COPD) and CNS through business development initiatives such as acquisition of Labrys Biologics in 2014 and Auspex Pharmaceuticals, Inc. in 2015.

Pfizer, Inc.

Pfizer, Inc. operates through two business segments: Pfizer Innovative Health and Pfizer Essential Health. The company has been issued 129 patents in the U.S. and 1,807 in the rest of the world for its products. It offers products in multiple therapeutic areas such as endocrinology, neurology, immunology, oncology, HIV, rare diseases, and hematology in more than 125 countries. Pfizer, Inc. has developed a strong supply chain network, which is directly responsible for addressing the patients needs. With technological advancements, the company tracks movement of products throughout the entire supply chain.

Sanofi

Sanofi is a global provider of health care solutions. The company has broad product portfolio that caters to areas such as rare diseases, multiple sclerosis, oncology, immunology, infectious diseases, diabetes, cardiovascular diseases, vaccines, and consumer health care. Sanofi focuses on acquisitions, in-licensing, and collaborations with key players in the market to reinforce its product pipeline. The company emphasizes on strategic reshaping of the product portfolio in order to strengthen its position in developed and emerging markets.

Global Z-drugs Market Dynamics

Large Patient Pool of Sleep Disorder Drives Demand for Z-drugs

Sleep disorder is a health concern for a larger percentage of the general population of the world. According to the Journal of Family Medicine and Primary Care, prevalence of sleep disorder is 10% to 30% of the global population, and insomnia in particular is on the rise. It is common in older adults, women, and people with medical and mental ill health. Such large population base of sleep disorder, especially insomnia, drives demand for Z-drugs.

Major Side Effects of Z-drugs to Hamper Market

Users of nonbenzodiazepines have reportedly experienced side effects such as short-term memory loss, sleepwalking, sleep driving, dizziness, headache, back pain, and rashes. This induces them to stop taking the drugs for long-term treatment, which in turn hampers sales of the drugs.

North America Dominated Global Z-drugs Market in 2018

According to the National Sleep Foundation, insomnia is the most common sleep disorder in the U.S. Moreover, around 40 million people in North America are affected by insomnia each year. The foundation also stated that prevalence of insomnia has increased among women and older adults in the region. Availability of drugs, high awareness about the effects of sleep disorder, and high prevalence of sleep disorders drive demand for Z-drugs in North America.

For More Details, Request A PDF Brochure Report @https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=71355

Global Z-drugs Market Segmentation

In terms of, the global Z-drugs market can be classified into:

Based on application, the global Z-drugs market can be categorized into:

In terms of distribution channel, the global Z-drugs market can be divided into:

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New Investments Expected To Boost The Z-drugs Market Between ' 2019' And '2027' Dagoretti News - Dagoretti News

Immunology

Surprising discovery could mean one-size-fits-all cancer treatment; researcher says nobody believed this c – OregonLive

January 22, 2020 medical

Not so long ago, people had trouble even saying the word. They whispered it, with a shudder, or simply called it the C-word.

Treatments have come a long way from the days when a cancer diagnosis was a near-certain death sentence. Survival rates have dramatically increased in recent decades for many types of the disease.

Still, cancer remains fearsome and has resisted all attempts to eradicate it.

Now researchers at Waless Cardiff University have made a surprising discovery about the immune system they believe could lead to a pan-cancer cure. Their work indicates that a newly identified T-cell in the blood can be genetically modified, or reprogrammed, to kill a large variety of cancers without harming healthy tissue.

As the researchers put it in a peer-reviewed paper in Nature Immunology: the targeting of cancer cells would allow immune destruction of malignancies in all individuals.

Thats right -- all individuals.

It raises the prospect of a one-size-fits-all cancer treatment, a single type of T-cell that could be capable of destroying many different types of cancers across the population, Cardiff University professor and lead author Andrew Sewell said in a university statement this week.

He added:

Previously nobody believed this could be possible.

Cancer experts not involved in the research say this is indeed an exciting development, with one calling it a transformative new finding. But they caution its early days. The process has been tested in the laboratory and in animals but not yet in humans.

At the moment, University of Manchester immunology professor Daniel Davis told the BBC, this is very basic research and not close to actual medicines for patients.

Whats unique about this newly discovered T-cell, Cardiff University said in a statement about the research, is that it sports a receptor that can recognize many types of cancer through a molecule called MR1 that, unlike previously known cell-surface molecules, does not vary in the human population -- meaning it is a hugely attractive new target for immunotherapies.

Sewell acknowledges there are plenty of hurdles to overcome, but he says the T-cell discovery opens up an exciting new frontier in the fight against cancer.

Read the research in Immunology Nature.

-- Douglas Perry

@douglasmperry

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Immunology

Antiviral treatments inspire new kind of cancer drug | Stanford News – Stanford University News

January 22, 2020 medical

Stanford virologist Jeffrey Glenn did not set out to tackle cancer. For years, he and his lab have worked to develop new ways of battling viruses like the ones that cause hepatitis delta and the common cold but the lessons theyve learned fighting viruses has led to a new kind of drug that has been effective at treating cancer in mice.

Jeffrey Glenn, professor of medicine and of microbiology and immunology, has spent years developing new ways to disrupt normal cellular processes in viruses. This work has led to drugs that can shrink and prevent the spread of tumors in mice. (Image credit: Courtesy of Stanford Medicine)

The underlying idea, Glenn said, is to disrupt otherwise normal cellular processes that both viruses and some cancer cells rely on to grow and spread. Now, tests in mice show that drugs based on that idea can shrink tumors and prevent their spread. The scientists from Stanford, the University of Texas, Baylor College of Medicine and the University of California, San Francisco, published their findings Jan. 22 in Science Translational Medicine.

Finding the new drug could not have happened without an unusual series of events and collaborations that spanned several academic disciplines, said Glenn, professor of medicine and of microbiology and immunology, whose lab developed the compounds with the assistance of Stanford ChEM-Hs Medicinal Chemistry Knowledge Center and support from ViRx@Stanford, an NIH-sponsored Center of Excellence for Translational Research led by Glenn.

Weve been working for many years on potent drugs that we had shown were important for viruses, said Glenn, who is also a member of Stanford Bio-X, the Maternal & Child Health Research Institute and ChEM-H. This is just an important target that hasnt really been appreciated in cancer, and we had the perfect drugs to get this started.

Originally, when they were looking for new ways to stop viruses such as hepatitis delta, Glenn and colleagues thought they might try a sort of end run around the virus and target cell functions that viruses hijack to replicate and spread. That way, even if a virus does infect a cell, thats more or less the end of it.

Glenns approach worked. In 2015, he and colleagues at the National Institutes of Health showed that the new approach prevented hepatitis delta from replicating and releasing new copies of the virus in patients. Later, they modified their strategy to attack enterovirus 71, which is best known for causing hand, foot and mouth disease but can also lead to devastating polio-like paralysis symptoms in children.

Glenn and his lab have continued to develop antiviral drugs, but their focus changed somewhat when their antiviral efforts caught the attention of Jonathan Kurie, a professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center. Kurie had learned that the same cellular processes Glenn and colleagues had successfully shut down was also involved in metastasis. After reading a paper describing the earliest compounds Glenn and his colleagues had developed, he wrote Glenn asking for some of the drug.

I told him we had much better molecules now, and we have known for a long time that they would also work in cancer, Glenn said, and he sent along two new compounds that he had developed with Mark Smith, who heads the Medicinal Chemistry Knowledge Center.

In the new paper, the team shows that their hunch was correct the same drugs Glenn, Smith and colleagues were developing to treat enterovirus can also treat certain kinds of cancers, at least in mice and human cancer cells in a lab dish.

In mouse studies, a drug the team tested reduced how often a human cancer implanted into the mouse in one lung spread to the second lung. With another compound, there were no detectable metastases at all, and both drugs reduced the size of tumors in the first lung. Human breast cancers growing in mice also shrunk in half after just one week of treatment.

The team also looked at an earlier drug developed in collaboration with Kevan Shokat, a professor of cellular and molecular pharmacology at the University of California, San Francisco, and a professor of chemistry at the University of California, Berkeley. That drug, they found, also curbed cell growth in human lung cancer cell lines. The team also gained some insight into which mice and one day, they hope, humans might benefit the most from the new drugs. They found that mice with extra copies of a particular gene responded much better to the drugs.

Now, Glenn said, My goal is to take this all the way to the clinic.

Glenn said the teams success is due in part to a significant shift in the last few years in what his lab does, building on an infectious brew of researchers from a range of academic disciplines.

I think thats the secret thing, having chemists physically in the lab with biologists, virologists and physician-scientists, Glenn said. Weve leveraged the special enabling environment of Stanford to create a unique group that has never existed before here or in academia. Its allowed things to happen that just wouldnt have happened otherwise.

That team is also starting to think about new ways to use their drugs, for example in combination with existing therapies to make them better against drug-resistant tumors, which might be susceptible to a new approach. Weve shown a proof of concept, and I think this could be useful in many cancers.

Additional Stanford authors are Edward Pham, a postdoctoral fellow in Glenns lab and a ChEM-H Physician-Scientist Research Fellow; Kaustabh Basu, a graduate student in chemistry; and research associates Khanh Nguyen and Grace Lam. Researchers from Baylor College of Medicine, the University of California, San Francisco, the University of Texas MD Anderson Cancer Center and the University of Texas Medical Branch contributed to the study.

The research was supported by grants from the National Institutes of Health, the Lung Cancer Research Foundation and the Department of Defense.

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

Immunology

supported scientists reverse HIV and SIV latency in two animal models – National Institutes of Health

January 22, 2020 medical

News Release

Wednesday, January 22, 2020

Findings represent progress toward an HIV cure.

In a range of experiments, scientists have reactivated resting immune cells that were latently infected with HIV or its monkey relative, SIV, in cells in the bloodstream and a variety of tissues in animals. As a result, the cells started making copies of the viruses, which could potentially be neutralized by anti-HIV drugs and the immune system. This advance, published today in two papers in the journal Nature, marks progress toward a widely accessible cure for HIV.

The new research was conducted by investigators from the Collaboratory of AIDS Researchers for Eradication (CARE) based at the University of North Carolina at Chapel Hill and from the Emory Consortium for Innovative AIDS Research (E-CIAR) in Nonhuman Primates, both funded by the National Institutes of Health. Scientists from ViiV Healthcare and Qura Therapeutics collaborated on the research. CARE is part of the Martin Delaney Collaboratories for HIV Cure Research, the flagship NIH-supported HIV cure research program. The joint efforts of scientists from a variety of specialties made the new findings possible.

A simple, safe and scalable cure for HIV is an aspirational goal that, if achieved, would accelerate progress toward ending the HIV pandemic, said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of NIH. These new findings help sustain our cautious optimism that an HIV cure is possible.

While consistent antiretroviral therapy (ART) maintains the health of people living with HIV and prevents transmission of the virus, it is not a cure. Developing an HIV cure has been extremely difficult due to the persistence of viral reservoirs, where the virus hides from the immune system. These reservoirs consist of HIV-infected cells containing HIV genetic material that can generate new virus particles if a persons treatment is interrupted. The cells have entered a resting state that they maintain until they are activated to produce the virus. The immune system cannot recognize and kill HIV-infected cells in a resting state, and ART has no effect on them.

Consequently, scientists have been attempting to activate the HIV reservoir so therapeutic agents or an enhanced immune system can recognize and kill the infected cells, eliminating HIV. This strategy is often called kick and kill. Previous attempts to reactivate or kick the HIV reservoir worked well in the laboratory but were either ineffective or too toxic when tested in animals and people.

One of todays reports describes the testing of a compound called AZD5582, which belongs to a class of molecules that have proven safe as experimental cancer therapeutics.

CARE scientists obtained 20 mice with human immune systems, infected the animals with HIV, and then gave them ART that suppressed the virus. Next, the scientists injected AZD5582 into 10 of the mice and a placebo into the other 10.

Within 48 hours, high levels of HIV RNA were detected in the blood of six of the AZD5582-treated mice. HIV RNA levels in resting immune cells of the bone marrow, thymic organoid, lymph node, spleen, liver and lung were up to 24-fold higher in the AZD5582-treated mice than in the controls. This indicated that AZD5582 had activated resting cells in the HIV reservoir throughout the treated mice. The compound did not cause toxicity in the mice or activate their immune systems.

The E-CIAR and CARE investigators also obtained 21 rhesus macaques, infected them with SIV and gave them suppressive ART. More than a year after the monkeys began ART, the scientists gave 12 of them weekly intravenous infusions of AZD5582 for either three or 10 weeks.

The level of SIV increased in the blood of five of the nine monkeys (55%) that received 10 doses of AZD5582 and in none of the three monkeys that received fewer doses. Thus, SIV levels increased in five of 12 monkeys (42%) overall, even as they remained on ART. SIV RNA levels in resting immune cells from the monkeys lymph nodes were significantly higher in animals treated with 10 doses of AZD5582 than in the nine monkeys that did not receive the compound. The investigators found AZD5582 treatment to be safe for most of the monkeys. The scientists did not detect a consistent reduction in the size of SIV reservoir in the AZD5582-treated monkeys, however, suggesting that it may be necessary to pair the compound with another agent to kill activated reservoir cells.

The researchers have begun additional animal studies to determine the best dose and timing of treatment and to be sure AZD5582 activates the reservoirs of many different HIV and SIV strains. It also will be important to test other compounds in the same class as AZD5582 to determine which might work best in humans, according to the scientists. If the results of these follow-up studies are successful, a preliminary clinical trial of treatment with AZD5582 or a related compound in people living with HIV may follow.

This study was led by J. Victor Garcia, Ph.D., Ann Chahroudi, M.D., Ph.D., and Richard Dunham, Ph.D. Dr. Garcia is director of the International Center for the Advancement of Translational Science, an Oliver Smithies Investigator and a professor of medicine, microbiology and immunology at University of North Carolina at Chapel Hill. Dr. Chahroudi is an associate professor of pediatrics in the division of pediatric infectious diseases at Emory University School of Medicineand director of the Emory + Children's Center for Childhood Infections and Vaccines. Dr. Dunham is a director at ViiV Healthcare and an adjunct assistant professor at University of North Carolina at Chapel Hill.

The other new report published today describes how a combination of two agents strongly activated the SIV reservoir in ART-treated rhesus macaques and the HIV reservoir in ART-treated mice with human immune systems. One agent, an antibody called MT807R1, depletes the body of immune cells called CD8+ T cells. The other agent is an engineered protein complex called N-803, a more powerful version of a naturally occurring molecule that activates certain immune cells to fight pathogens.

E-CIAR scientists obtained 35 rhesus macaques, infected them with SIV and gave them ART, which suppressed the virus in 33 of the animals. At least a year after ART began, the scientists gave seven monkeys N-803 alone, 14 monkeys MT807R1 alone, and 14 monkeys both MT807R1 and N-803.

N-803 alone had no impact on the SIV reservoir. MT807R1 alone led to a moderate but significant increase in the level of SIV in the animals blood (their viral load). But the combination of MT807R1 plus N-803 led to a robust and persistent increase in the SIV viral load of all 14 animals even the six in which fewer than three copies of SIV were detected before the experimental treatment began.

CARE scientists at UNC replicated these outcomes in 23 mice that had been given human immune systems, infected with HIV and given suppressive ART.

In addition, investigators demonstrated in cell culture that N-803 could reactivate human immune cells latently infected with HIV, but that adding CD8+ T cells to the culture suppressed the latency-reversing activity of N-803.

Taken together, the findings illustrate that CD8+ T cells play a role in maintaining the SIV reservoir in monkeys. The scientists hope to clarify exactly how CD8+ T cells do this so they can develop a latency-reversing strategy that does not require eliminating all CD8+ T cells and is thus gentler on the body.

This research was led by Guido Silvestri, M.D. Dr. Silvestri is the Georgia Research Alliance Eminent Scholar in comparative pathology, professor and interim chair of the department of pathology and laboratory medicine at Emory University School of Medicine, and chief of the division of microbiology & immunology at Yerkes National Primate Research Center.

CARE is funded by NIAID with additional support from the National Institute on Drug Abuse, the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, all part of NIH. E-CIAR is also funded by NIAID with additional support from the NIH Office of Research Infrastructure Programs.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

CC Nixon, M Mavigner et al. Systemic HIV and SIV latency reversal via non-canonical NF-B signalling in vivo. Nature DOI: 10.1038/s41586-020-1951-3 (2020).

JB McBrien et al. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8+ cells. Nature DOI: 10.1038/s41586-020-1946-0 (2020).

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supported scientists reverse HIV and SIV latency in two animal models - National Institutes of Health

Immunology

Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosi | TCRM – Dove Medical Press

January 22, 2020 medical

Jean Kim,1,2 Robert Naclerio1

1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Medicine: Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence: Jean KimJohns Hopkins Bayview Medical Center, 4940 Eastern Ave, Suite A102B, Baltimore, MD 21224, USATel +1 410-550-0460Fax +1 410-550-2871Email jeankim@jhmi.edu

Abstract: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which sub-population of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.

Keywords: chronic rhinosinusitis, nasal polyps, Type 2 inflammation, dupilumab

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosi | TCRM - Dove Medical Press

Immunology

Johns Hopkins Researchers: Climate Change Threatens to Unlock New Microbes and Increase Heat-Related Illness and Death – Newswise

January 22, 2020 medical

MEDIA CONTACT

Available for logged-in reporters only

Newswise The Journal of Clinical Investigation (JCI) recently published Viewpoint articles by Johns Hopkins University School of Medicine professors who warn that global climate change is likely to unlock dangerous new microbes, as well as threaten humans ability to regulate body temperature.

Johns Hopkins Bloomberg Distinguished Professors Rexford Ahima, M.D., Ph.D., and Arturo Casadevall, M.D., Ph.D., M.S., along with William Dietz, M.D., Ph.D., director of the George Washington Universitys Sumner M. Redstone Global Center for Prevention and Wellness, and Susan Pacheco, M.D., associate professor in the Department of Pediatrics at the University of Texas Health Science Center at Houston, authored journal articles relevant to their fields that detail how rising temperatures around the world pose dangerous threats to humanity.

Ahima, director of Johns Hopkins Division of Endocrinology, Diabetes and Metabolism, wrote in the journal that global warming threatens human thermoregulation and survival.

Ahima explains that people generate body heat and have the capacity to regulate their temperature within a few degrees. But as heat waves become more common, more severe, and longer, we expect to see more heat-related illnesses and deaths, he writes.

Ahima cites a recent study that examined global heat-related mortality, pointing out that tropical and subtropical countries and regions will experience the sharpest surge in illness and death stemming from higher temperatures, while the United States and Europe can also expect increases.

Casadevalls article explores the specter of new infectious diseases as a result of the changing climate.

Given that microbes can adapt to higher temperatures, writes the professor of molecular microbiology and immunology, and infectious diseases, at Johns Hopkins schools of medicine and public health, there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious diseases.

Endothermy allows humans and other warm-blooded mammals to maintain high temperatures that can protect against infectious diseases by inhibiting many types of microbes.

Casadevall cites a particular climate threat from the fungal kingdom.

We have proposed that global warming will lead many fungal species to adapt to higher temperatures, he writes, and some with pathogenic potential for humans will break through the defensive barrier provided by endothermy.

As an example, Casadevall points to the rise of Candida auris, a species of fungus identified in 2009 and called a catastrophic threat by the U.S. Centers for Disease Control and Prevention in 2017.

The nearly simultaneous emergence of Candida auris on three continents, an event proposed to result from global warming, has raised the specter that increased warmth by itself will trigger adaptations on certain microbes to make them pathogenic for humans.

Casadevall says that, while fungi present the most immediate threat, other microbes also adapt to evolving conditions such as temperature. He writes that the conceptual threat originally identified with fungi, and exemplified by C. auris as the canary in the coal mine, applies across the microbial world.

Dietzs article addresses climate change and malnutrition, calling obesity, undernutrition and climate change a syndemic, or multiple epidemics that interact and share common underlying social or economic determinants and policy drivers. In her article, Pacheco discusses climate changes adverse consequences regarding pregnancy and maternal, fetal and child health.

In all four JCI Viewpoint articles, long-term strategies are urged to reduce greenhouse gas emissions and slow the trend of rising temperatures.

SEE ORIGINAL STUDY

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Johns Hopkins Researchers: Climate Change Threatens to Unlock New Microbes and Increase Heat-Related Illness and Death - Newswise

Immunology

What’s on Your Shelf? Recommended Reading in the New Year – Healio

January 22, 2020 medical

Over the past few years in this column, I have occasionally shouted out a book I have read and I have occasionally been rewarded by more than a few of my readers then sharing with me their thoughts and experiences of these same works. As the first editorial of 2020, I thought it might be fun to go to my bookshelf and share a number of the titles I have read over the past year.

I always read both nonfiction and fiction at the same time, but I am only going to give you my nonfiction picks. To get my fiction reading list, you will have to buy me a glass of wine so I can wave my hands and tell you why I picked certain books. A second caveat is that I must be truthful and tell you that I often buy the Kindle version of a nonfiction book first, and if I really like it, then I buy the real deal because I like to write and scribble in my books. I am not sure what that says about me but thats the way it is and virtually all have come into my passion this way.

Leonard H.Calabrese

There is no total unifying theme of the nine books I am recommending to you but, after looking at this stack, I think I found a few threads. My intention in this column is to give you enough information that will tempt you to pick one or more up on the basis of our shared interests. The first theme surrounds my work, namely the field of immunology in all its glory. There are three books that deal with my field and thus one may wonder what there could be in books written for the lay public that would make heart a card-carrying immunology guys heart sing to read? The answer is easy. Its all about the humanity.

In An Elegant Defense, Matt Richtel recounts stories of real patients with HIV, rheumatoid arthritis, and cancer intersecting with therapeutic advances in the field, and the enormous impact these changes have had on them. In The Breakthrough, Charles Graeber details the backstory of the people behind the development of checkpoint inhibitors, including many colorful interviews with Nobel Laureate James P. Allison, PhD even for me, actively working in the field, this was a terrific read.

Finally, the real sleeper in the immunology cassette, is The Beautiful Cure by Daniel M. Davis, which despite not garnering the press it deserves, in my opinion is a brilliant treatise on the evolution of the field of immunology over the past century. The book is written in scholarly fashion, but laced with terrific backstories in the style of The Gene by Siddhartha Mukherjee. Read it!

Switching gears, The Compassionate Connection by David Rakel and Suggestible You by Eric Vance are all about placebo science and the role of interpersonal relationships in building wellness and healing. Both of these are great reads and I am planning on a cover story/roundtable in the spring on placebo science in rheumatology. See how this works now?

The Longevity Diet by Valter Longo, PhD, a leading researcher in aging/longevity research is a terrific read on something we all share an interest in namely how to eat and living a long life. I find choosing books in the wellness field often problematic given the myriad of bugnutty offerings out there, but I assure you, Dr. Longo is a scientist in the truest sense of the word. I recently hosted him at my 2019 Cleveland Clinic Biologic Therapies VIII Summit, a presentation you will be able to watch when it posts on our website in the near future.

In my previous editorials in February 2019 and April 2019, I have already discussed the profound impact of The Empathy Effect by Helen Reiss, MD, and Deep Medicine by Eric Topol, MD, so I will not expound on them again if you havent picked up by now, please do. Perhaps counterintuitively, I believe these books on empathy and artificial intelligence are intimately related. As I have written in the past, one of the most exciting and challenging areas of investigation lying ahead is how to bring empathy to the growing onslaught of AI, machine learning and technology. We must figure this out.

Finally, why did Leonardo Da Vinci, by the noted biographer Walter Isaacson, make it to my bedside reading table? There are many reasons, perhaps prominent among them that 2019 was the 500th anniversary of the death of the most curious man with the greatest mind the world has ever known. Probably more important is a passion to learn about him instilled by a friend and a physician, humanist and Da Vinci scholar, Sal Mangione, MD, from Thomas Jefferson University.

I have heard Dr. Mangione speak on Da Vinci many times, and he has also graced our Medical Grand Rounds podium frequently discussing art, observation and humanism. His passion for the life, work and genius of Leonardo Da Vinci is quite infectious, and the book is a great start to understanding the master Thank you Sal, I am hooked.

These are my nonfiction picks from the last year tell me about yours through Twitter at @LCalabreseDO or email me at calabrl@ccf.org.

Disclosures: Calabrese reports consulting relationships with AbbVie, Centecor Biopharmaceutical, Crescendo Bioscience, GlaxoSmithKline, Horizon Pharma, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals and UCB.

Leonard H.Calabrese

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These are my nonfiction picks from the last year tell me about yours through Twitter at @LCalabreseDO or email me at calabrl@ccf.org.

Immunology

Hope for patients with a rare genetic condition linked to severe infections – Newswise

January 22, 2020 medical

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Journal of Allergy and Clinical Immunology, January 2020

Newswise A team of researchers at CHU Sainte-Justine and Universit de Montral has shed light on the mechanisms that underlie a rare genetic condition by creating the first cellular model of the disease. The study's findings were published today in the Journal of Allergy and Clinical Immunology.

Chronic granulomatous disease (CGD) is a rare hereditary condition that affects one in every 217,000 people worldwide and typically strikes patients at an early age.

It is a primary innate immune defect that typically leads to severe, recurrent infections caused by bacteria and fungi, as well as potentially disabling lung inflammation or inflammatory colitis similar to Crohns disease, said senior author Dr.FabienTouzot, a clinical assistant professor in pediatric medicine at UdeM and researcher in pediatric immunology and hematology at CHU Sainte-Justine.

Currently, patients are forced to take antibiotics and anti-inflammatory drugs for the rest of their lives.

Gene editing shows the way forward

To better understand the mechanisms that trigger inflammation in patients with CGD, Touzot and his research team created the very first cellular model of the disease in their labs at CHU Sainte-Justine. They then used a technique known as gene editing to recreate and introduce into their model a genetic mutation that causes the disease. This allowed them to model the inflammatory response observed in patients and to study its mechanisms.

CGD is a hereditary illness caused by mutations in the NADPH oxidase enzyme. These mutations prevent white blood cells from working properly and, as a result, the patients body can no longer defend itself against certain kinds of bacteria and fungi, said researcher Aissa Benyoucef, the studys first author.

More than 90% of affected patients have inflammation that appears to be unrelated to infectious agents," he added. "Treating this inflammation is difficult, since it can put patients at increased risk of infection, which can sometimes be fatal. A better understanding of the mechanisms underlying the disease could help us develop new and more effective treatment strategies.

The research team showed that restoring NADPH oxydase function in defective cells would put the immune process back on track, thereby proving that this genetic mutation plays a direct role in causing inflammation.

CHU Sainte-Justine is one of Quebecs leading centres of expertise in rare genetic diseases," said Touzot. "Were proud to serve patients by expanding the knowledge base in this area and by contributing to the development of precision medicine."

The new cellular model will be useful for the development of targeted treatments that are less toxic and more effective in treating inflammation, significantly improving patient quality of life, according to the researchers.

About this study

CRISPR gene-engineered CYBBko THP-1 cell lines highlight the crucial role of NADPH-induced reactive oxygen species for regulating inflammasome activation was published in the January 2020 edition of the Journal of Allergy and Clinical Immunology. The first author is Aissa Benyoucef, PhD, a lab employee under the supervision of Dr. Fabien Touzot. The senior author is Dr. Touzot, MD, PhD, a clinical assistant professor at Universit de Montreals Department of Pediatrics and clinician-researcher in pediatric immunology and hematology at CHU Sainte-Justine. The study was paid by a CHU Sainte-Justine Research Centre start-up fund and by Fondation Charles-Bruneau.

About the CHU Sainte-Justine Research Centre

The CHU Saint-Justine Research Centre is a flagship institution in mother-child research affiliated with Universit de Montral. Focused on the discovery of innovative means of prevention, less intrusive and faster treatments and promising avenues of personalized medicine, it brings together more than 210 researchers, including more than 90 clinical researchers, as well as 450 graduate students and postdoctoral fellows. The centre is an integral part of the Centre hospitalier universitaire Sainte-Justine, the largest mother-child centre in Canada. Details at https://research.chusj.org/en/Home