Cell Biology

Princeton Researchers Catalog the Gut Microbiomes Impact on Medications – SciTechDaily

Study investigates potential for the intestinal microbial community to alter drug safety and efficacy.

Researchers at Princeton University have developed a systematic approach for evaluating how the microbial community in our intestines can chemically transform, or metabolize, oral medications in ways that impact their safety and efficacy.

The new methodology provides a more complete picture of how gut bacteria metabolize drugs, and could aid the development of medications that are more effective, have fewer side effects, and are personalized to an individuals microbiome.

The study was published today (June 10, 2020) in the journal Cell.

Researchers at Princeton created a system for evaluating how the bodys gut bacteria alter the safety and efficacy of everyday drugs. The system can be used in pharmaceutical research to improve drug discovery and development. Credit: Janie Kim. Published in Cell

Previous studies have examined how single species of gut bacteria can metabolize oral medications. The new framework enables evaluation of a persons entire intestinal microbial community at once.

Basically, we do not run and hide from the complexity of the microbiome, but instead, we embrace it, said Mohamed S. Donia, assistant professor of molecular biology. This approach allows us to gain a holistic and more realistic view of the microbiomes contribution to drug metabolism.

The team used the approach to evaluate the gut microbiomes effect on hundreds of common medications already on the market. The intestines are the primary region where pills and liquid medications are absorbed into the body.

The researchers identified 57 cases in which gut bacteria can alter existing oral medications. Eighty percent of those had not been previously reported, emphasizing the potential of the method for revealing unknown drug-microbiome interactions.

These alterations range from converting the medicine into an inactive state which can reduce its efficacy to converting the drug into a form that is toxic, potentially causing side effects.

The framework could aid drug discovery by identifying potential drug-microbiome interactions early in development, informing formulation changes. The approach can also help during clinical trials to better analyze the toxicity and efficacy of drugs being tested.

The intestines are home to hundreds of species of bacteria. The makeup of these communities what kinds of bacteria and how many of each species can vary considerably from person to person.

This inter-person variability underscores why studying a single bacterial species makes it impossible to compare the microbiomes metabolism of drugs between individuals, Donia said. We need to study the entire intestinal microbial community.

The researchers found that some peoples microbiomes had little effect on a given drug, while other microbiomes had a significant effect, demonstrating how important the community of bacteria rather than just single species is on drug metabolism.

Everyones microbiome is unique, and we were able to see this in our study, said Bahar Javdan, an M.D.-Ph.D. student in molecular biology and a co-first author on the study. We observed three main categories drugs that were consistently metabolized by all the microbiomes in our study, drugs that were metabolized by some and not by others, and drugs that were not subject to any microbiome-derived metabolism.

The methodological approach could be valuable for personalizing treatment to the microbiome of each patient. For example, the framework could help predict how a certain drug will behave, and suggest changes to the therapeutic strategy if undesired effects are predicted.

This is a case where medicine and ecology collide, said Jaime Lopez, a graduate student in the Lewis-Sigler Institute for Integrative Genomics and a co-first author on the study, who contributed the computational and quantitative analysis of the data. The bacteria in these microbial communities help each other survive, and they influence each others enzymatic profiles. This is something you would never capture if you didnt study it in a community.

The framework involves four steps for systematically evaluating the intestinal microbiomes effect on drugs.

First, the researchers collected 21 fecal samples collected from anonymous donors and cataloged the bacterial species living in each individual. They found that the donors each had a unique microbial community living in their guts, and that the majority of these personalized communities can be grown in a lab culturing system that they developed.

Next, they tested 575 FDA-approved drugs to see if they are chemically modified by one of the 21 cultured microbiomes, and then tested a subset of the drugs with all the cultured microbiomes. Here, they found microbiome-derived metabolites that had never been previously reported, as well as ones that have been reported in humans and associated with side effects but their origins were unknown. They found cases where all the donor microbiomes performed the same reactions on the drug, and others where only a subset did.

Then they examined the mechanisms by which some of the modified drugs are altered by the cultured microbiomes. To understand exactly how the transformations occurred, they traced the source of the chemical transformations to particular bacterial species and to particular genes within those bacteria. They also showed that the microbiome-derived metabolism reactions that are discovered in this manner can be recapitulated in a mouse model, the first step in adapting the approach for human drug development.

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Reference: Personalized mapping of drug metabolism by the human gut microbiome by Bahar Javdan, Jaime G. Lopez, Pranatchareeya Chankhamjon, Ying-Chiang J.Lee, Raphaella Hull, Qihao Wu, Xiaojuan Wang, Seema Chatterjee and Mohamed S. Donia, 10 June 10, 2020, Cell.DOI: 10.1016/j.cell.2020.05.001

Additional contributors to the study were postdoctoral research associates Pranatchareeya Chankhamjon, Qihao Wu and Xiaojuan Wang; graduate student in molecular biology Ying-Chiang J. Lee, graduate student at Cambridge University Raphaella Hull; and Seema Chatterjee, research lab manager.

Funding for this study was provided by the Princeton Department of Molecular Biology, the National Institutes of Health, the New Jersey Commission on Cancer and the National Science Foundation.

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Princeton Researchers Catalog the Gut Microbiomes Impact on Medications - SciTechDaily

Cell Biology

The 2019 3Rs prize awarded to two pieces of novel research – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Jun 10 2020

The 2019 3Rs prize has been jointly awarded to Dr Francesca Nunn and Dr Marta Shahbazi for papers describing research that reduces the number of chickens and mice respectively. The 3Rs prize is awarded by the NC3Rs and sponsored by GSK.

- Nunn F, et al (2019). A novel, high-welfare methodology for evaluating poultry red mite interventions in vivo. Veterinary Parasitology. 267:42-46. doi.org/10.1016/j.vetpar.2019.01.011

- Shahbazi, MN, et al (2017). Pluripotent state transitions coordinate morphogenesis in mouse and human embryos. Nature. 552:239-243. doi.org/10.1038/nature24675

Dr Francesca Nunn, a post-doctoral scientist at the Moredun Research Institute

Francesca and colleagues developed and optimized a device to improve the testing of treatments against poultry red mites, reducing the number of hens used in field trials.

Poultry red mites are a blood feeding ectoparasite. They are a global problem for the egg industry, affecting the welfare of laying hens through irritation and anaemia. Mites are controlled using chemicals, however, repeated use has led to resistance and recent research efforts have focused on developing vaccines and novel biopesticides.

Assessment of vaccine control methods is initially done in vitro using blood assays before field trials are conducted, with 750 to 800 hens exposed to mites for each vaccine candidate, with an adjuvant control group. In vitro assays can be unreliable, for example, due to high levels of non-specific mite mortality. As a consequence, vaccine efficacy measured in vitro is not always translated into mite population reduction in field trials.

Francesca developed an "on-hen" mite feeding device that improves the screening of vaccine candidates to avoid unnecessary field trials. The device consists of a mesh pouch containing approximately 100 mites that have been starved for three weeks. The pouch is fitted to the thigh of the vaccinated hen - the mesh is large enough to allow the mites' mouth parts to access the hen's skin but small enough to contain the mites. Four hens are used per vaccine candidate and after three hours, the mesh is removed and the mites are recovered and maintained in 96-well plates for up to six days to assess mortality.

The device has already been used to provide data that has prevented seven vaccines and vaccine delivery methods from going into field trials. The initial pre-screening using the on-hen device involved 56 hens in total, each exposed to 100 mites for three periods of three hours - the field studies would have used almost 5,500 birds exposed to 10,000 mites for 100 days.

The on-hen device has been used by academic and commercial laboratories in the UK and internationally. By varying the size of the mesh, the device has the potential to be used in research on other parasites.

Dr Marta Shahbazi, a research leader at the MRC Laboratory of Molecular Biology

Marta and colleagues have developed advanced 3D cultures of human and mouse embryonic stem cells to mimic the development of the embryo at implantation and the subsequent morphogenesis and formation of the amniotic cavity, providing an opportunity to replace and reduce the use of live mice in some developmental biology studies.

Implantation of an embryo into the uterus is a critical step with a high rate of pregnancies lost at this stage. Studying implantation and other early embryonic events is technically and ethically challenging. The majority of work is carried out in mice, typically genetically modified animals where associated surgery and breeding of large numbers of animals are required.

Marta's research has shown that it is possible to minimise this use with reproducible and novel 3D cultures of mouse embryonic stem cells that reliably mimic development at the time of, and beyond, implantation, avoiding the need for recipient mice for embryo transfer and the subsequent culling of animals to access early stage embryos.

Marta and colleagues have previously described an in vitro method to culture human embryos beyond the point of implantation, overcoming the technical challenges that have traditionally limited the use of human embryos in research. The winning paper builds on this by reporting comparative functional experiments using mouse and human embryonic stem cell 3D cultures that have identified key factors involved in the remodelling of the embryo at implantation to form the amniotic cavity. This has revealed a previously unknown link between cell potency and tissue shape, with a loss of stem cell "nave pluripotency" (that is the ability to become any cell type in the organism) triggering the formation of the cavity and developmental progression of the embryo. The use of the 3D cultures for these studies replaced the use of 500 mice and importantly by demonstrating that they can be used to answer fundamental biological questions, the research has led to multiple groups worldwide adopting the cultures, further reducing the use of animals.

Professor Kevin Shakesheff, Chair of the NC3Rs Board and 3Rs Prize Panel said: "The vibrancy of research into the 3Rs was evident from the quality and breadth of the papers we considered. The winning papers and authors demonstrate that 3Rs research can the quality of science and unlock new types of experiments with wide applicability. Both papers are making an impact across the world and the prizes are richly deserved."

GSK is incredibly proud of being able to support the important work done by the NC3Rs and it was a real pleasure to participate in the presentation of these awards as the quality of the science was truly outstanding. The ambition to reduce, refine and replace that is at the core of the work that we are happily able to recognise in the winners is more crucial than ever. The need to ensure that every intervention, measurement and outcome helps to move science and the development of medicines forward is especially critical today in the context of Covid19 where great, reproducible, impactful science has to lead the way."

Dr Rab Prinjha, GSK Vice President of Adaptive Immunity and Immuno-epigenetics

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Immunology

European Academy of Allergy and Clinical Immunology: Launch of the EAACI Guidelines for the Use of Biologicals in Patients With Severe Asthma -…

ZRICH, June 8, 2020 /PRNewswire/ -- EAACI has launched its Guidelines for the use of Biologicals in Patients with Severe Asthma at the EAACI Digital Congress 2020.

Prof. Marek Jutel, EAACI President began by highlighting the significant burden of severe asthma on patients, families and healthcare systems. "Management of severe asthma proves to be difficult due to disease heterogeneity, coexisting comorbidities and especially because of complexities in care pathways and differences in national and regional healthcare systems. Better understanding of the mechanisms of the disease has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, many unmet needs remain: how to select a certain biological as they all target overlapping disease phenotypes? How to enhance response? What are the best strategies to enhance the respondent's rate? What is the optimal duration of treatment and its cost-effectiveness? And what is the appropriate regimen - in the clinic or home-based?"

What is novel in the EAACI guidelines for the management of severe asthma is the inclusion of the GRADE approach in formulating recommendations for each biological and asthma outcome, separate recommendations for exacerbations, for lung function and more.

"It is clear that biologicals in the context of severe asthma is a very rapidly evolving field. After the first EAACI position paper on Biologicals and allergic diseases, these EAACI Guidelines for the use of Biologicals in Patients with Severe Asthma represent a desk reference tool of utmost importance for healthcare providers, patients, regulators and healthcare systems providing specific recommendations for each biological in the context of each independent outcome," says Prof. Oscar Palomares, Complutense University of Madrid, Past Chair of EAACI Biologicals Working Group, current EAACI ExCom member and Biologicals Guidelines Project Co-Chair.

A management algorithm for the use of biologicals in the clinic is further proposed, together with future approaches and research priorities. "EAACI advocates for a triple decision chart based on phenotypic traits, biomarkers and outcomes, added to this is shared decision making to reset individual goals and define response together with the patient. Efficacy is tested after 4-6 months - if there is a response, intervention is to be continued according to the preset target and while continuously monitoring for safety. Real life evidence must be collected through registries, real world trials and health economics indicators as the basis for the next steps. If the response is suboptimal it is important to look at the airway inflammation and to the airway hyperreactvity. If the eosinophilic inflammation persists, several factors can be improved, for example adherence to background controller treatment or other options can be considers such as switching to a biological targeting a different path, or checking for other immune mechanisms. If neutrophilic inflammation is present macrolides can be considered. If there is no inflammation non-T2 asthma approaches like dual bronchodilators and in very selective cases bronchial thermoplasty can be considered," says Prof. Dr. Ioana Agache, University of Brasov Romania, Biologicals Guidelines Project Co-Chair and EAACI Past President.

The rising use of biologicals (monoclonal antibodies) in modern medicine, their remarkable potential and possible challenges were also discussed at the EAACI Digital Congress 2020 by its Special Guest, Sir Gregory Paul Winter, Nobel Prize Winner for Biochemistry in 2018.

"For inflammatory disease monoclonal antibodies are finding their place on the front line. Although inflammatory diseases such as severe asthma can be treated with chemical drugs such as corticosteroids their broad mechanism of action may also bring a range of undesirable side effects including fluid retention, hypertension and bone loss, particularly with extended use. Ideally treatments should have a more specific mode of action and avoid these side effects. That is why monoclonal antibodies which have such specific modes of action in blocking the interaction of key proteins or receptors are so attractive. And the availability of a range of therapeutic monoclonal antibodies against proteins involved in inflammation provides the opportunity to identify in the clinic those targets which are most relevant. Over the last 30 years biologicals have become increasingly important in medicine. The limitations in early use of biologicals were overcome by the recombinant DNA technology leading to a tsunami of therapeutic monoclonal antibodies. These biologicals are of high efficiency and exquisite specificity, they have a long half-life in serum and properties and functions can be tailored to order. Their impact has already been immense and likely to become greater still," says Sir Gregory Winter, University of Cambridge, Nobel Prize Laureate 2018.

Under these promising auspices, EAACI hopes its new Guidelines will be a cornerstone for clinicians, researchers, scientific societies and medical agencies in the years to come.

About EAACI:

The European Academy of Allergy and Clinical Immunology (EAACI) is an association of clinicians, researchers and allied health professionals founded in 1956. EAACI is dedicated to improving the health of people affected by allergic diseases. With more 12 000 members from 124 countries and over 75 National Allergy Societies, EAACI is the primary source of expertise in Europe and worldwide for all aspects of allergy.

Logo - https://mma.prnewswire.com/media/1177661/EAACI_Digital_Congress_2020_Logo.jpg

Contact: EAACI Headquarters Hagenholzstrasse 111, 3rd Floor 8050 Zurich CH- Switzerland Tel: +41799561865 communications@eaaci.org http://www.eaaci.org

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European Academy of Allergy and Clinical Immunology: Launch of the EAACI Guidelines for the Use of Biologicals in Patients With Severe Asthma -...

Immunology

Immune modulation can cure severe and often fatal fungal infection in children – News-Medical.Net

In the June 11 issue of the New England Journal of Medicine, a team of UCLA physicians and scientists describes the first case of immune modulation being used to cure a severe and often fatal fungal infection. The team "retuned" a 4-year-old's immune system so that it could fight off disseminated coccidioidomycosis.

The case, originally reported by UCLA in 2019, could pave the way for a new treatment for the infection, which affects hundreds of Americans each year, primarily in the Southwest, and kills approximately 40% of the people who contract it.

The technique described in the study could also suggest a new paradigm for treating other severe fungal infections, bacterial infections such as tuberculosis, and severe viral infections such as influenza and COVID-19.

"Immune modulation isn't currently part of the strategy with any of these severe infections," said Dr. Manish Butte, the report's senior author, who holds the E. Richard Stiehm Endowed Chair in Pediatric Allergy, Immunology and Rheumatology at the David Geffen School of Medicine at UCLA.

"Our case suggests that rather than hoping to get the upper hand with more and more antibiotics or antifungals, we can have some success by combining these established approaches with the new idea of programming the patient's immune response to better fight the infection."

Each year, more than 100,000 people are infected with Coccidioides fungi, which reside in the soils of California, Arizona and West Texas. Most people who are infected are asymptomatic, and about 20,000 experience the minor respiratory illness commonly known as Valley fever.

The vast majority of people with Valley fever respond well to antifungal medications, but approximately 1% of the infections progress to disseminated coccidioidomycosis, in which the infection spreads rapidly throughout the body, leading to bone and tissue damage, and in many cases death.

Historically, severe infections have been seen as bad luck. Doctors haven't looked at how we can harness the immune systems of these patients to fight the infection."

Dr Manish Butte, Study Senior Author, University of California Los Angeles (UCLA) Health Sciences

According to a 2019 study in the International Journal of Environmental Research and Public Health, California spends between $700 million and $900 million a year in direct and indirect costs related to the care of people infected by the cocci fungus, including more than $300 million to care for the approximately 200 people with disseminated coccidioidomycosis.

The boy who was treated by Butte and his team had previously been treated with high doses of multiple antifungal medicines, but by the time he arrived at UCLA, he could barely walk or talk and required a feeding tube to eat.

When UCLA physicians homed in on the patient's immune system, they concluded that his T cells -; the white blood cells that play a key role in the body's immune response -; were failing to properly recognize the invading fungus. The T cells were responding as though the infection was a parasitic infection rather than a fungal one.

That prompted the team to supplement the boy's antifungal medications with an immune stimulator called interferon-gamma. And Dr. Maria Garcia-Lloret, a pediatric allergist and immunologist, suggested adding yet another medication, dupilumab, which was developed as a medication for allergic diseases and had never before been used to treat infections.

Dupilumab is a prescription drug that has not been approved by the FDA as a treatment for disseminated coccidioidomycosis.

The combination of immune modulators restored the proper programming to the patient's T cells -; and the boy's infection went away in a month.

The UCLA research team cites that the immunomodulatory approach has the potential to enhance the ability of patients to clear other types of fungal, bacterial, and viral infections that are not responding to established therapies.

In partnership with the Bakersfield, California-based Valley Fever Institute and the drugs' manufacturers -; Horizon Therapeutics, Regeneron Pharmaceuticals and Sanofi Genzyme -; the UCLA researchers are planning to test the two drugs on other people with disseminated coccidioidomycosis. They also plan to study the approach for treating other types of severe infections.

Source:

Journal reference:

Tsai, M., et al. (2020) Disseminated Coccidioidomycosis Treated with Interferon- and Dupilumab. The New England Journal of Medicine. doi.org/10.1056/NEJMoa2000024.

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Immunology

UW-Madison on quest to cure "COVID toes" in children – WMTV

MADISON, Wis. (WMTV)-- UW-Madison researchers are now trying to figure why some children suffer from a condition called "COVID toes."

In a release, UW Health said on Wednesday that dermatologists at the university and elsewhere have seen an uptick in red to purple bruise-like blisters and bumps on otherwise healthy children.

Some doctors thought that there could be a link to the painful condition and COVID-19, coining the phrase "COVID toes."

The issue could also be connected to a rare skin condition called "chilblains." That condition results in a higher protein that helps kill viral infections, according to the UW.

At UW Health, all of the children with COVID toes have been healthy and lacked both current and previous symptoms of COVID-19. We want to better understand how their immune system may have been able to combat the virus," said Dr Lisa Arkin, assistant professor of dermatology and pediatrics at the UW's School of Medicine and Public Health.

During the study, researchers will collect samples from a number of participants, including blood, saliva, and archived tissue from previous procedures.

Our approach is unique, instead of studying the sickest patients we aim to study those that stayed relatively healthy, once we figure that out we can use this science to treat the sickest most vulnerable patients, said Dr. Beth Drolet, chair of dermatology at the UW's School of Medicine and Public Health. We have leading experts in dermatology, immunology, rheumatology, genetics and virology all working together to get answers as fast as we can.

To learn more about how to participate in this research study, call (608) 287-2640 or (608) 287-2006 or email clinicaltrials@dermatology.wisc.edu.

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UW-Madison on quest to cure "COVID toes" in children - WMTV

Immunology

COVID-19 cases will go up as Alberta reopens many activities: health experts – EverythingGP

By Canadian Press

Jun 10, 2020

EDMONTON Health experts say it makes sense for Alberta to take the next step in reopening itseconomy, but warn there will be an uptick in COVID-19 cases due to the inability to physically distance in some situations.

Premier Jason Kenneyannounced on Tuesday thateverything from casinos, gyms and arenasto spas, movie theatres andpools will be allowed to reopen on Friday.

Dr. Christopher Mody, whos the head of microbiology, immunology and infectious disease at the Cumming School of Medicine at the University of Calgary, says Albertas case numbers support moving forward.

There were 356 active cases on Tuesday, with 46 people in hospital and six of those in intensive care.

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COVID-19 cases will go up as Alberta reopens many activities: health experts - EverythingGP

Immunology

Immune system can be re-wired to prevent attack of healthy cells, study finds – News-Medical.net

Reviewed by Emily Henderson, B.Sc.Jun 9 2020

The body's immune system can be re-wired to prevent it from recognizing its own proteins which, when attacked by the body, can cause autoimmune diseases like multiple sclerosis, a significant new study by UK scientists has found.

Autoimmune diseases are caused when the immune system loses its normal focus on fighting infections or disease within and instead begins to attack otherwise healthy cells within the body. In the case of multiple sclerosis (MS), the body attacks proteins in myelin - the fatty insulation-like tissue wrapped around nerves - which causes the nerves to lose control over muscles.

Led by a multi-disciplinary team from the University of Birmingham, scientists examined the intricate mechanisms of the T-cells (or white blood cells) that control the body's immune system and found that the cells could be 're-trained' to stop them attacking the body's own cells. In the case of multiple sclerosis, this would prevent the body from attacking the Myelin Basic Protein (MBP) by reprogramming the immune system to recognize the protein as part of itself.

Supported by the Medical Research Council, the two-part study, published today in Cell Reports, was a collaboration between two research groups led by Professor David Wraith from the Institute of Immunology and Immunotherapy and Professor Peter Cockerill from the Institute of Cancer and Genomic Sciences.

The first stage, led by Professor Wraith showed that the immune system can be tricked into recognising MBP by presenting it with repeated doses of a highly soluble fragment of the protein that the white blood cells respond to. By repeatedly injecting the same fragment of MBP, the process whereby the immune system learns to distinguish between the body's own proteins and those that are foreign can be mimicked. The process, which is a similar type of immunotherapy to that previously used to desensitise people against allergies, showed that the white blood cells that recognise MBP switched from attacking the proteins to actually protecting the body.

The second stage, saw gene regulation specialists led by Professor Peter Cockerill probe deep within the white blood cells that react to MBP to show how genes are rewired in response to this form of immunotherapy to fundamentally re-programme the immune system. The repeated exposure to the same protein fragment triggered a response that turns on genes that silence the immune system instead of activating it. These cells then had a memory of this exposure to MBP embedded in the genes to stop them setting off an immune response. When T cells are made tolerant, other genes which function to activate the immune system remain silent.

Professor David Wraith said: "These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat."

This study has led us to finally understand the underlying basis of immunotherapies which desensitise the immune system"

Professor Peter Cockerill, Institute of Cancer and Genomic Sciences

Further longer term clinical trials will be needed to determine whether antigen-specific immunotherapies can indeed deliver lasting benefits. If this is successful, the study published today will be the first study defining the actual mechanisms of how T-cells can be made tolerant to the body's own proteins in a context that may lead to further advances in the battle to overcome autoimmunity.

Source:

Journal reference:

Bevington, S.L., et al. (2020) Chromatin Priming Renders T Cell ToleranceAssociated Genes Sensitive to Activation below the Signaling Threshold for Immune Response Genes. Cell Reports. doi.org/10.1016/j.celrep.2020.107748.

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Immune system can be re-wired to prevent attack of healthy cells, study finds - News-Medical.net

Immunology

Collaborating in Innovative Medical R&D to combat the pandemic, Alphamab Oncology and Institut Pasteur Shanghai Announce Partnership to Co-develop…

DetailsCategory: AntibodiesPublished on Wednesday, 10 June 2020 11:06Hits: 223

SUZHOU, China I June 9, 2020 I Alphamab Oncology (stock code: 9966 HK) announced that Jiangsu Alphamab Biopharmaceuticals Co., Ltd. ("Jiangsu Alphamab"), a wholly-owned subsidiary of the Company, has entered a partnership agreement with Institut Pasteur of Shanghai, Chinese Academy of Sciences ("Institut Pasteur Shanghai") on the co-development, manufacturing and commercialization of therapeutic antibody for Corona Virus Disease 2019 (COVID-19) worldwide.

According to a report on June8, more than 7.10 million people have been diagnosed with COVID-19 infection worldwide, but there are still no vaccines or medicines available for prevention or treatment. Neutralizing antibody targeting proteins on the surface of virus can effectively inhibit the virus' binding and entry into target cells to block infection, therefore it can be considered to be useful to protect or treat patients with COVID-19 infection. Among various potential solutions, the optimized mixed antibodies solution not only amplify the therapeutic effect due to synergistic effect, but also can solve the virus escaping issue due to COVID-19 virus' mutation, and minimizes the risk of "Antibody-dependent enhancement".

This cooperation will fully leverage not only Institut Pasteur Shanghai 's prowess in research and development, and prior research findings in the area of infectious diseases, but also Alphamab Oncology's strong R&D and its proprietary Mixed Antibodies Platform, to develop COVID-19 neutralizing antibody with good safety and high neutralizing activity, complete clinical trials soon to provide antibody treatment options, effectively improve the prevention capabilities, reduce the mortality rate, and contribute to disease prevention and control for China and the world. Meanwhile, Pasteur's global R&D network could also help expedite the completion of clinical trial.

According to the agreement, Alphamab Oncology and Institut Pasteur Shanghai will form a joint project team. Alphamab Oncology is responsible for providing its proprietary Mixed Antibodies Platform, constructing humanized antibodies and recombinant engineered cell lines, carrying out PK study, clinical trials, manufacturing, and commercialization. Institut Pasteur Shanghai is responsible for the comprehensive analysis of neutralizing activity of COVID-19 antibodies.

Dr. Ting Xu, Founder, Chairman and CEO of Alphamab Oncology commented, "Since the end of 2019, COVID-19 has ravaged the world and has become the major global public health issue. We plan to partner with Institut Pasteur Shanghai by leveraging our proprietary antibody technology platform, extensive experiences in antibody drug R&D and established manufacturing platform to accelerate the development of COVID-19 antibodies to combat COVID-19, prevent subsequent outbreaks and contribute to the further prevention and control of this epidemic."

Dr. Hong Tang, Director General and Legal Representative of Institut Pasteur Shanghai commented, "Since the outbreak of the Coronavirus, the Institut Pasteur Shanghai has been focusing on R&D Projects including virus detection and origin tracing, antibody drug and vaccine, and has achieved quite a few progress. This partnership with Alphamab Oncology on COVID-19 neutralizing antibody drughas demonstrated not only the innovation capability of our research and development team, but also a result of the reform of Chinese Academy of Sciences and the capable platform of Shanghai Science and Innovation Center. Our institute will collaborate with industry players to accelerate drug development and contribute to the prevention and control of pandemic as soon as possible."

About Alphamab Oncology

Alphamab Oncology is a biopharmaceutical company focusing on innovative biologics medicine for oncology. On December 12, 2019, the Company was listed in the mainboard of Hong Kong Stock Exchange with stock code 9966.

Alphamab has fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline consists of eight anti-cancer drug candidates, four of which have advanced into Phase I III clinical development phases in China, US and Japan.

The Company also has state-of-the-art manufacturing capability designed and built to meet NMPA and EU/FDA's cGMP standards.

Alphamab Oncology is committed to further develop its robust pipeline in oncology/immunology to benefit patients around the world. Visit http://www.alphamabonc.com for more information.

About Institut Pasteur Shanghai

Institut Pasteur of Shanghai of Chinese Academy of Sciences was established in October 11, 2004.It is the only national research institute dedicated to the basic research and development of relevant technologies for human infectious diseases within the Academy. The Institute focuses on key scientific subject such as the fundamental laws of pathogenic microorganisms' activities, and the pathogenic mechanism of major infectious diseases, to promotes the innovation and development of etiology, immunology and vaccinology to solve key issues such as the discovery of pathogen and biological treatment (antibodies, vaccines, etc. ), with a focus on providing scientific and technological support and solutions for public health and biosecurity of China.It is actively participating the building of Shanghai Science and Innovation Center. The infectious diseases' prevention and treatment platform, a functional platform which it is responsible for, will provide solid scientific support for the prevention and control of infectious diseases in Shanghai and Yangtze River Delta Region in China.

SOURCE: Alphmab

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Collaborating in Innovative Medical R&D to combat the pandemic, Alphamab Oncology and Institut Pasteur Shanghai Announce Partnership to Co-develop...

Human Behavior

SIUE School of Education, Health and Human Behavior to host virtual discussion on dismantling institutionalized racism in higher education – Alton…

SIUE School of Education, Health and Human Behavior to host virtual discussion on dismantling institutionalized racism in higher education

EDWARDSVILLE Civil unrest has swept the globe as racial injustices and systemic oppression have again been brought to the forefront following the murder of George Floyd in Minneapolis. Protests, action movements, and calls for listening and learning span the world.

The Southern Illinois University Edwardsville School of Education, Health and Human Behavior (SEHHB) is responding with a significant opportunity for teaching and learning, as is its mission, by hosting the first in a series of virtual panels, podcasts, and community discussions on the important topic of Dismantling Institutional Racism in Higher Education. Supported by the Provosts Office and the East St. Louis Center, the panel discussion will explore how institutions of higher education (leadership, faculty, staff and students) can serve to disrupt systemic racism and white supremacy embedded into organizational life and culture.

These systems are consistently reified through everyday organizational practices that dehumanize black, indigenous and other persons of color (BIPOC). The goal of the series is to clearly identify the systems, structures, and practices that maintain institutional racism and white supremacy in PK20 institutions of education. Through collective bodies, we will explore actionable steps to identify, disrupt and ultimately dismantle systems of white supremacy. Meaningful change which restores the lost opportunities of BIPOC requires that the people of institutions engage in self-reflection, examination of practices and policies, and actions that translate to structural and systemic change. Anything less would follow a dehumanizing trend of educators and educator leaders perpetuating the status quo.

The virtual panel is free and will take place via Zoom beginning at 2 p.m. Thursday, June 11, and last for approximately 2 hours. Interested participants should register at SIUEs offical website and a zoom meeting link will be sent to registrants prior to the event.

We invite all who are concerned, questioning or frustrated to join in this critical discussion about how institutions can work towards dismantling institutionalized racism, said SEHHB Dean Robin Hughes, PhD, whose describes her own academic practice and expertise as shaped through an activist and critical race theoretical lens - or way of knowing, thinking and living.

It is crucial that we use and share our personal and professional experiences, significant research findings and collective commitment to the Universitys mission and values to take positive and effective action to dismantle institutional racism that happens everywhere, she emphasized.

Hughes designated a collective of scholar-activists to coordinate this important discussion. The group represents some SIUE scholars whose research agenda and activism focuses on race and other isms. Current members include the SEHHBs Jennifer Hernandez, PhD; Jessica Krim, EdD; J.T. Snipes, PhD; and Nate Williams, PhD.

Along with Dr. Nate Williams, speakers at the virtual panel will include:

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SIUE School of Education, Health and Human Behavior to host virtual discussion on dismantling institutionalized racism in higher education - Alton...

Human Behavior

Researchers investigate the effects of isolation in zebrafish – News-Medical.net

Reviewed by Emily Henderson, B.Sc.Jun 10 2020

Over the past few months at least half of the world's population has been affected by some form of lockdown due to COVID-19, and many of us are experiencing the impact of social isolation. Loneliness affects both mental and physical health, but counterintuitively it can also result in a decreased desire for social interaction. To understand the mechanics of this paradox, UCL researchers based at the Wolfson Institute and the Sainsbury Wellcome Centre investigated social behavior in zebrafish. Their results are published in eLife.

Most zebrafish demonstrate pro-social behavior, but approximately 10% are 'loner' fish who are averse to social cues and demonstrate different brain activity than their pro-social siblings. However, even typically social zebrafish avoid social interaction after a period of isolation. PhD students Hande Tunbak and Mireya Vazquez-Prada, Postdoctoral Research Fellow Thomas Ryan, Dr Adam Kampff and Sir Henry Dale Wellcome Fellow Elena Dreosti set out to test whether the brain activity of isolated zebrafish mimics that of loner fish or whether other forces were at play.

To investigate the effects of isolation, the researchers isolated typically social zebrafish from other fish for a period of two days and then compared their brain activity to zebrafish who demonstrated aversion to social interaction without having been isolated. The isolated fish demonstrated sensitivity to stimuli and had increased activity in brain regions related to stress and anxiety. These effects of isolation were quickly overcome when the fish received a drug that reduces anxiety.

The differences between loner fish and their siblings were found mostly in the hypothalamus, the region of the brain responsible for social rewards. The loner fish hypothalamus did not demonstrate the same pattern of activation during social exposure as its typical counterparts, indicating that loner fish do not experience rewards in the same way as typical fish during social interactions.

By contrast, 'lonely' fish--those that demonstrated typical social behavior and were isolated--demonstrated hypersensitivity to stimuli and activation of brain regions associated with stress and anxiety. Lonely fish experienced actively negative outcomes from social interaction whereas loner fish simply did not experience reward.

A detailed view of the zebrafish brain can provide important clues for all of us currently experiencing the effects of social isolation."

Dr. Elena Dreosti

Our understanding of the neural mechanisms of social behavior are limited, but we do know that zebrafish and humans share a fundamental drive for social interaction that is controlled by similar brain structures. Although human behavior is much more complex, understanding how this basic social drive arises--and how it is affected by isolation--is a necessary step towards understanding the impact of the social environment on human brains and behavior. The zebrafish, which is completely transparent throughout early development, offers neuroscientists a detailed view of its brain circuitry.

We won't all be loners after lockdown, but we will be anxious upon returning to our normal social lives. As we emerge from lockdown, we should be aware of this new sensitivity and anxiety, but recognize that overcoming it is necessary for returning to a normal, healthy, social existence.

Source:

Journal reference:

Tunbak, H., et al. (2020) Whole-brain mapping of socially isolated zebrafish reveals that lonely fish are not loners. eLife. doi.org/10.7554/eLife.55863.

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Researchers investigate the effects of isolation in zebrafish - News-Medical.net