Biochemistry

Global Molecular Diagnostics Tests & Reagents Market: Business Overview, Regional Analysis, By Product, By End Users, Key Players And Forecast…

Molecular Diagnostics Tests & Reagents Market

Los Angeles, United State, ,-The research study presented here is a brilliant compilation of different types of analysis of critical aspects of the global Molecular Diagnostics Tests & Reagents market. It sheds light on how the global Molecular Diagnostics Tests & Reagents market is expected to grow during the course of the forecast period. With SWOT analysis and Porters Five Forces analysis, it gives a deep explanation of the strengths and weaknesses of the global Molecular Diagnostics Tests & Reagents market and different players operating therein. The authors of the report have also provided qualitative and quantitative analyses of several microeconomic and macroeconomic factors impacting the global Molecular Diagnostics Tests & Reagents market. In addition, the research study helps to understand the changes in the industry supply chain, manufacturing process and cost, sales scenarios, and dynamics of the global Molecular Diagnostics Tests & Reagents market.

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Each player studied in the report is profiled while taking into account its production, market value, sales, gross margin, market share, recent developments, and marketing and business strategies. Besides giving a broad study of the drivers, restraints, trends, and opportunities of the global Molecular Diagnostics Tests & Reagents market, the report offers an individual, detailed analysis of important regions such as North America, Europe, and Asia Pacific. Furthermore, important segments of the global Molecular Diagnostics Tests & Reagents market are studied in great detail with key focus on their market share, CAGR, and other vital factors.

Key Players:

Siemens Healthcare, Johnson and Johnson, Becton Dickinson, Abbott Laboratories, Roche Diagnostics, Beckman Coulter Inc, Thermo Scientific, Cobas, Caprion, Merck Millipore, Aptiv Solution, Danaher Corporation, Biomerieux, Bio-Rad Laboratories, Ortho Clinical Diagnostics, Sysmex Corporation, Mindray, Shanghai Kehua Bio-engineering, BioSino Bio-technology, Beijing Leadman Biochemistry, DAAN Gene

Type Segments:

Professional Diagnostic, Molecular Diagnostic, Diabetes Monitoring

Application Segments:

Diabetes, Infectious Diseases, Oncology, Cardiology, HIV, Other

Regional Segments

Table of Contents

1 Market Overview of Molecular Diagnostics Tests & Reagents 1.1 Molecular Diagnostics Tests & Reagents Market Overview1.1.1 Molecular Diagnostics Tests & Reagents Product Scope1.1.2 Market Status and Outlook 1.2 Global Molecular Diagnostics Tests & Reagents Market Size Overview by Region 2015 VS 2020 VS 2026 1.3 Global Molecular Diagnostics Tests & Reagents Market Size by Region (2015-2026) 1.4 Global Molecular Diagnostics Tests & Reagents Historic Market Size by Region (2015-2020) 1.5 Global Molecular Diagnostics Tests & Reagents Market Size Forecast by Region (2021-2026) 1.6 Key Regions Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026)1.6.1 North America Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026)1.6.2 Europe Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026)1.6.3 China Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026)1.6.4 Rest of Asia Pacific Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026)1.6.5 Latin America Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026)1.6.6 Middle East & Africa Molecular Diagnostics Tests & Reagents Market Size YoY Growth (2015-2026) 1.7 Coronavirus Disease 2019 (Covid-19): Molecular Diagnostics Tests & Reagents Industry Impact1.7.1 How the Covid-19 is Affecting the Molecular Diagnostics Tests & Reagents Industry1.7.1.1 Molecular Diagnostics Tests & Reagents Business Impact Assessment Covid-191.7.1.2 Supply Chain Challenges1.7.1.3 COVID-19s Impact On Crude Oil and Refined Products1.7.2 Market Trends and Molecular Diagnostics Tests & Reagents Potential Opportunities in the COVID-19 Landscape1.7.3 Measures / Proposal against Covid-191.7.3.1 Government Measures to Combat Covid-19 Impact1.7.3.2 Proposal for Molecular Diagnostics Tests & Reagents Players to Combat Covid-19 Impact 2 Molecular Diagnostics Tests & Reagents Market Overview by Type 2.1 Global Molecular Diagnostics Tests & Reagents Market Size by Type: 2015 VS 2020 VS 2026 2.2 Global Molecular Diagnostics Tests & Reagents Historic Market Size by Type (2015-2020) 2.3 Global Molecular Diagnostics Tests & Reagents Forecasted Market Size by Type (2021-2026) 2.4 Professional Diagnostic 2.5 Molecular Diagnostic 2.6 Diabetes Monitoring 3 Molecular Diagnostics Tests & Reagents Market Overview by Type 3.1 Global Molecular Diagnostics Tests & Reagents Market Size by Application: 2015 VS 2020 VS 2026 3.2 Global Molecular Diagnostics Tests & Reagents Historic Market Size by Application (2015-2020) 3.3 Global Molecular Diagnostics Tests & Reagents Forecasted Market Size by Application (2021-2026) 3.4 Diabetes 3.5 Infectious Diseases 3.6 Oncology 3.7 Cardiology 3.8 HIV 3.9 Other 4 Global Molecular Diagnostics Tests & Reagents Competition Analysis by Players 4.1 Global Molecular Diagnostics Tests & Reagents Market Size (Million US$) by Players (2015-2020) 4.2 Global Top Manufacturers by Company Type (Tier 1, Tier 2 and Tier 3) (based on the Revenue in Molecular Diagnostics Tests & Reagents as of 2019) 4.3 Date of Key Manufacturers Enter into Molecular Diagnostics Tests & Reagents Market 4.4 Global Top Players Molecular Diagnostics Tests & Reagents Headquarters and Area Served 4.5 Key Players Molecular Diagnostics Tests & Reagents Product Solution and Service 4.6 Competitive Status4.6.1 Molecular Diagnostics Tests & Reagents Market Concentration Rate4.6.2 Mergers & Acquisitions, Expansion Plans 5 Company (Top Players) Profiles and Key Data 5.1 Siemens Healthcare5.1.1 Siemens Healthcare Profile5.1.2 Siemens Healthcare Main Business and Companys Total Revenue5.1.3 Siemens Healthcare Products, Services and Solutions5.1.4 Siemens Healthcare Revenue (US$ Million) (2015-2020)5.1.5 Siemens Healthcare Recent Developments 5.2 Johnson and Johnson5.2.1 Johnson and Johnson Profile5.2.2 Johnson and Johnson Main Business and Companys Total Revenue5.2.3 Johnson and Johnson Products, Services and Solutions5.2.4 Johnson and Johnson Revenue (US$ Million) (2015-2020)5.2.5 Johnson and Johnson Recent Developments 5.3 Becton Dickinson5.5.1 Becton Dickinson Profile5.3.2 Becton Dickinson Main Business and Companys Total Revenue5.3.3 Becton Dickinson Products, Services and Solutions5.3.4 Becton Dickinson Revenue (US$ Million) (2015-2020)5.3.5 Abbott Laboratories Recent Developments 5.4 Abbott Laboratories5.4.1 Abbott Laboratories Profile5.4.2 Abbott Laboratories Main Business and Companys Total Revenue5.4.3 Abbott Laboratories Products, Services and Solutions5.4.4 Abbott Laboratories Revenue (US$ Million) (2015-2020)5.4.5 Abbott Laboratories Recent Developments 5.5 Roche Diagnostics5.5.1 Roche Diagnostics Profile5.5.2 Roche Diagnostics Main Business and Companys Total Revenue5.5.3 Roche Diagnostics Products, Services and Solutions5.5.4 Roche Diagnostics Revenue (US$ Million) (2015-2020)5.5.5 Roche Diagnostics Recent Developments 5.6 Beckman Coulter Inc5.6.1 Beckman Coulter Inc Profile5.6.2 Beckman Coulter Inc Main Business and Companys Total Revenue5.6.3 Beckman Coulter Inc Products, Services and Solutions5.6.4 Beckman Coulter Inc Revenue (US$ Million) (2015-2020)5.6.5 Beckman Coulter Inc Recent Developments 5.7 Thermo Scientific5.7.1 Thermo Scientific Profile5.7.2 Thermo Scientific Main Business and Companys Total Revenue5.7.3 Thermo Scientific Products, Services and Solutions5.7.4 Thermo Scientific Revenue (US$ Million) (2015-2020)5.7.5 Thermo Scientific Recent Developments 5.8 Cobas5.8.1 Cobas Profile5.8.2 Cobas Main Business and Companys Total Revenue5.8.3 Cobas Products, Services and Solutions5.8.4 Cobas Revenue (US$ Million) (2015-2020)5.8.5 Cobas Recent Developments 5.9 Caprion5.9.1 Caprion Profile5.9.2 Caprion Main Business and Companys Total Revenue5.9.3 Caprion Products, Services and Solutions5.9.4 Caprion Revenue (US$ Million) (2015-2020)5.9.5 Caprion Recent Developments 5.10 Merck Millipore5.10.1 Merck Millipore Profile5.10.2 Merck Millipore Main Business and Companys Total Revenue5.10.3 Merck Millipore Products, Services and Solutions5.10.4 Merck Millipore Revenue (US$ Million) (2015-2020)5.10.5 Merck Millipore Recent Developments 5.11 Aptiv Solution5.11.1 Aptiv Solution Profile5.11.2 Aptiv Solution Main Business and Companys Total Revenue5.11.3 Aptiv Solution Products, Services and Solutions5.11.4 Aptiv Solution Revenue (US$ Million) (2015-2020)5.11.5 Aptiv Solution Recent Developments 5.12 Danaher Corporation5.12.1 Danaher Corporation Profile5.12.2 Danaher Corporation Main Business and Companys Total Revenue5.12.3 Danaher Corporation Products, Services and Solutions5.12.4 Danaher Corporation Revenue (US$ Million) (2015-2020)5.12.5 Danaher Corporation Recent Developments 5.13 Biomerieux5.13.1 Biomerieux Profile5.13.2 Biomerieux Main Business and Companys Total Revenue5.13.3 Biomerieux Products, Services and Solutions5.13.4 Biomerieux Revenue (US$ Million) (2015-2020)5.13.5 Biomerieux Recent Developments 5.14 Bio-Rad Laboratories5.14.1 Bio-Rad Laboratories Profile5.14.2 Bio-Rad Laboratories Main Business and Companys Total Revenue5.14.3 Bio-Rad Laboratories Products, Services and Solutions5.14.4 Bio-Rad Laboratories Revenue (US$ Million) (2015-2020)5.14.5 Bio-Rad Laboratories Recent Developments 5.15 Ortho Clinical Diagnostics5.15.1 Ortho Clinical Diagnostics Profile5.15.2 Ortho Clinical Diagnostics Main Business and Companys Total Revenue5.15.3 Ortho Clinical Diagnostics Products, Services and Solutions5.15.4 Ortho Clinical Diagnostics Revenue (US$ Million) (2015-2020)5.15.5 Ortho Clinical Diagnostics Recent Developments 5.16 Sysmex Corporation5.16.1 Sysmex Corporation Profile5.16.2 Sysmex Corporation Main Business and Companys Total Revenue5.16.3 Sysmex Corporation Products, Services and Solutions5.16.4 Sysmex Corporation Revenue (US$ Million) (2015-2020)5.16.5 Sysmex Corporation Recent Developments 5.17 Mindray5.17.1 Mindray Profile5.17.2 Mindray Main Business and Companys Total Revenue5.17.3 Mindray Products, Services and Solutions5.17.4 Mindray Revenue (US$ Million) (2015-2020)5.17.5 Mindray Recent Developments 5.18 Shanghai Kehua Bio-engineering5.18.1 Shanghai Kehua Bio-engineering Profile5.18.2 Shanghai Kehua Bio-engineering Main Business and Companys Total Revenue5.18.3 Shanghai Kehua Bio-engineering Products, Services and Solutions5.18.4 Shanghai Kehua Bio-engineering Revenue (US$ Million) (2015-2020)5.18.5 Shanghai Kehua Bio-engineering Recent Developments 5.19 BioSino Bio-technology5.19.1 BioSino Bio-technology Profile5.19.2 BioSino Bio-technology Main Business and Companys Total Revenue5.19.3 BioSino Bio-technology Products, Services and Solutions5.19.4 BioSino Bio-technology Revenue (US$ Million) (2015-2020)5.19.5 BioSino Bio-technology Recent Developments 5.20 Beijing Leadman Biochemistry5.20.1 Beijing Leadman Biochemistry Profile5.20.2 Beijing Leadman Biochemistry Main Business and Companys Total Revenue5.20.3 Beijing Leadman Biochemistry Products, Services and Solutions5.20.4 Beijing Leadman Biochemistry Revenue (US$ Million) (2015-2020)5.20.5 Beijing Leadman Biochemistry Recent Developments 5.21 DAAN Gene5.21.1 DAAN Gene Profile5.21.2 DAAN Gene Main Business and Companys Total Revenue5.21.3 DAAN Gene Products, Services and Solutions5.21.4 DAAN Gene Revenue (US$ Million) (2015-2020)5.21.5 DAAN Gene Recent Developments 6 North America Molecular Diagnostics Tests & Reagents by Players and by Application 6.1 North America Molecular Diagnostics Tests & Reagents Market Size and Market Share by Players (2015-2020) 6.2 North America Molecular Diagnostics Tests & Reagents Market Size by Application (2015-2020) 7 Europe Molecular Diagnostics Tests & Reagents by Players and by Application 7.1 Europe Molecular Diagnostics Tests & Reagents Market Size and Market Share by Players (2015-2020) 7.2 Europe Molecular Diagnostics Tests & Reagents Market Size by Application (2015-2020) 8 China Molecular Diagnostics Tests & Reagents by Players and by Application 8.1 China Molecular Diagnostics Tests & Reagents Market Size and Market Share by Players (2015-2020) 8.2 China Molecular Diagnostics Tests & Reagents Market Size by Application (2015-2020) 9 Rest of Asia Pacific Molecular Diagnostics Tests & Reagents by Players and by Application 9.1 Rest of Asia Pacific Molecular Diagnostics Tests & Reagents Market Size and Market Share by Players (2015-2020) 9.2 Rest of Asia Pacific Molecular Diagnostics Tests & Reagents Market Size by Application (2015-2020) 10 Latin America Molecular Diagnostics Tests & Reagents by Players and by Application 10.1 Latin America Molecular Diagnostics Tests & Reagents Market Size and Market Share by Players (2015-2020) 10.2 Latin America Molecular Diagnostics Tests & Reagents Market Size by Application (2015-2020) 11 Middle East & Africa Molecular Diagnostics Tests & Reagents by Players and by Application 11.1 Middle East & Africa Molecular Diagnostics Tests & Reagents Market Size and Market Share by Players (2015-2020) 11.2 Middle East & Africa Molecular Diagnostics Tests & Reagents Market Size by Application (2015-2020) 12 Molecular Diagnostics Tests & Reagents Market Dynamics 12.1 Industry Trends 12.2 Market Drivers 12.3 Market Challenges 12.4 Porters Five Forces Analysis 13 Research Finding /Conclusion 14 Methodology and Data Source 14.1 Methodology/Research Approach14.1.1 Research Programs/Design14.1.2 Market Size Estimation14.1.3 Market Breakdown and Data Triangulation 14.2 Data Source14.2.1 Secondary Sources14.2.2 Primary Sources 14.3 Disclaimer 14.4 Author List

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Global Molecular Diagnostics Tests & Reagents Market: Business Overview, Regional Analysis, By Product, By End Users, Key Players And Forecast...

Biochemistry

Ruby Ahaiwe ’21 Focuses Her Public Health Interest on Her Community – Bowdoin News

Before the pandemic, Ahaiwe was also planning a "huge walk for health," as she describes it, in which local people and health care providers walked from the hospital to the local government center to demand more resources for rural health care.

After it became clear that COVID-19 would make it impossible to fly to Nigeria, Ahaiwe established community liaisonsincluding friends and relativeswho could start to educate local people about the importance of taking advantage of local clinics.

"There is a heavy dependency on traditional medicine," Ahaiwe said, "which can work, but people should understand they have a wide range of options for medical care."

Her community partners have been putting up posters Ahaiwe has designed and printed that contain medical advice, such as the importance of handwashing.

The hospital also recently organized a COVID-19 awareness walk to educate community members about the seriousness of the virus. Ahaiwe donated part of her grant to buy face masks and pocket sanitizers to hand out to townspeople.

Working from afar this summer has been successful. But Ahaiwe is a bit worried about how well the community will receive her when she eventually does return to Nigeria. Though her family is from the village, they left the area when she was a child. "Some people might say, 'Who is this young girl telling us how to run our health?'"

To foster community buy-in to her health-outreach projects, Ahaiwe has contacted community leaders, including the local king."Hesaid it was good for the community that young people are coming back to invest in the community and that he would offer whatever support I need,"Ahaiwe said.

Her public health project is the kind of work Ahaiwe wants to dedicate her lifework to. At Bowdoin, she is majoring in biochemistry and minoring in Francophone studies. After college, she plans to earn a master's degree in public health to work in the area of preventative health care, "especially in places with disparities," she said. She would love to be based in Nigeria or somewhere else in Africa, she added.

"This is my focus," she said. "I am passionate about it."

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Ruby Ahaiwe '21 Focuses Her Public Health Interest on Her Community - Bowdoin News

Cell Biology

Molecular Structure of LRRK2 Gives Clues to Parkinson’s – Alzforum

28 Aug 2020

For the first time, researchers have solved the molecular structure of LRRK2, a major risk factor for Parkinsons and autoimmune diseases. Structural biologists at the University of California, San Diego, used innovative methods to provide two complementary views of the molecule. In the August 7 Cell, researchers led by Elizabeth Villa described the three-dimensional architecture of full-length, pathogenic LRRK2 inside cells. The protein formed filaments that corkscrewed around microtubules. Researchers led by Andres Leschziner isolated a fragment of wild-type LRRK2 suitable for cryoEM. In the August 19 Nature, their high-resolution molecular maps revealed that this portion of the protein folds to bring its kinase and GTPase domains into close proximity. The finding explains previous experimental data suggesting the two domains interact.

By combining data from both studies, the research groups determined that for LRRK2 to bind microtubules, its kinase has to be in a closed, or active, conformation. Pathogenic mutations, some of which are known to increase microtubule binding, appear to bias the molecule toward this shape. Leschziner and colleagues data hint that microtubule binding could contribute to toxicity, because LRRK2 filaments impede the passage of motor proteins down these highways, potentially causing traffic jams.

LRRK2 kinase inhibitors currently being tested as PD therapeutics may also trap the protein in this closed conformation.

Microtubule Decoration. Monomers of LRRK2 (black outline) join together to form a double helix of strands (gold and blue) that wrap around microtubules (gray). Viewed down the microtubule axis, each monomer assumes the same orientation with respect to the microtubule surface (bottom). [Courtesy of Watanabe et al., Cell.]

The new structures described in these two elegant studies represent a significant step forward in our understanding of LRRK2, Dario Alessi at the University of Dundee, Scotland, wrote to Alzforum (full comment below). The data provide new insights into how pathogenic mutations might exert their effects by promoting LRRK2 to adopt a closed conformation that is able to bind microtubule filaments.

A Peek at 3-D Structures in Their Native HabitatMutations in LRRK2 account for up to 10 percent of familial PD cases. In addition, the concentration of this protein is elevated in many cases of sporadic disease, hinting at a broad role in pathology (Di Maio et al., 2018). Yet how LRRK2 contributes to Parkinsons has remained murky. Besides being a kinase and GTPase, this large protein contains many other protein interaction domains (see diagram below). LRRK2 participates in numerous cellular processes, including vesicle trafficking, cell signaling, and autophagy, prompting a plethora of hypotheses about how it might cause harm (Oct 2012 news; Mar 2013 conference news).A structural map of the protein could help researchers decipher its function, but despite years of effort, LRRK2 has stubbornly resisted crystallization.

Villa and colleagues decided to flip the challenge of mapping LRRK2 on its head. Instead of trying to purify and crystallize the protein, they reasoned, why not simply image it in place? They took advantage of the fact that pathogenic LRRK2 is known to decorate microtubules, making it easy to find and visualize within the cell. Joint first authors Reika Watanabe, Robert Buschauer, and Jan Bhning expressed fluorescently tagged LRRK2 bearing the PD mutation I2020T in a kidney cell line, froze the cells, diced them into thin sections, and located LRRK2 on microtubules by correlating light and electron microscopy. Then they tilted the sections at different angles and imaged these decorated microtubules with an electron microscope in a process known as cryo-electron tomography. CryoET constructs three-dimensional structures from sequential two-dimensional images of surfaces (Luciet al., 2008). With this technology, the authors mapped microtubule-bound LRRK2 filaments to a resolution of 14 angstroms.

Notorious Multitasker. In addition to a Ras of complex (ROC) GTPase (green), and a kinase domain (pink), LRRK2 contains many protein-protein interaction domains. The C-terminal of ROC (COR) N and C domains regulate the GTPase. These are commonly called COR-A (yellow) and COR-B (orange). [Courtesy of Watanabe et al., Cell.]

To my knowledge, this is the first time someone has solved a structure inside a cell before it could be solved with biochemistry, Villa said. We took a technologically fancy but a biochemically lazy approach.

CryoET revealed LRRK2 molecules forming a double helix around each microtubule, like the spiraling stripes of a candy cane (see image at top). In these long daisy chains of LRRK2 proteins, each bound to the one behind it through their respective WD40 domains (yes, here WD40 is a glue, not a lubricant), and to the one in front of it through their respective COR-B domains. The proteins were oriented such that their C-terminal halves, containing both catalytic domains, were located near the microtubule surface, while their N-terminal portions floated off into the cytoplasm and could not be resolved by cryoET. This orientation left the ROC GTPase domain facing the microtubule surface, and the kinase exposed to cytosol (see image below). Structural modeling suggested that the kinase was in the closed conformation, although this detail could not be resolved visually.

Dual Dimerization. Two LRRK2 monomers (left) sitting on a microtubule (outline) link via their COR domains (yellow), leaving their kinases (pink) exposed to cytosol. Their WD40 domains (red) link to adjoining monomers (gray). Rotation to show the view along the microtubule axis (right) exposes the GTPase domain (green) nestled against the microtubule surface. [Courtesy of Watanabe et al., Cell.]

Villa believes her groups approach of using cryoET to scan molecules inside cells might help crack other recalcitrant structures, as well as provide clues to what proteins are doing in their native environment and how that changes during disease. Its the beginning of a new era of bridging structural and cellular biology, Villa said.

Close Contact. The C-terminal half of LRRK2 folds to bring its kinase (orange) and GTPase (green) into proximity. Common Parkinsons mutations are well-placed to modify this contact (right). [Courtesy of Deniston et al., Nature.]

A High-Resolution Glimpse of LRRK2s Business EndFor their part, Leschziner, co-corresponding author Samara Reck-Peterson, and colleagues took a different approach. Co-first author Sebastian Mathea in Stefan Knapps lab at Goethe University in Frankfurt had expressed the C-terminal half of wild-type human LRRK2 in insect cells, and found it was amenable to purification. Co-first author Colin Deniston imaged these molecules to 3.5 angstrom resolution by cryoEM. They determined that the molecule folded into a J shape that brought the ROC GTPase into close contact with the kinase domain (see image above). Previous studies had found that GTPase activity was essential for the kinase to function, but it was unclear how these domains interacted (Ito et al., 2007; West et al., 2007). In this protein fragment, the kinase assumed its open, catalytically inactive shape.

Intriguingly, the C-terminal tail of the WD40 domain formed a long -helix that extended along the backbone of the kinase, interacting with it at several points. Noting that this -helix contains at least one phosphorylation site, Leschziner speculated that modification of this tail might help regulate the shape of the kinase, perhaps switching it on and off.

Finally, the researchers overlaid their model onto the LRRK2 filaments described by Villa and colleagues to see if the structures matched. The monomer fit relatively well, but not perfectlythe COR domains clashed against those of the neighboring LRRK2s. When Leschziner and colleagues altered their structure to model a closed kinase domain, however, these steric clashes resolved (see image below). This finding suggested that an open conformation of the kinase would prevent microtubule binding, Leschziner said.

How Do Microtubules Fit In?Whether LRRK2 gloms onto microtubules under physiological conditions is unclear. In cultured cells containing endogenous, wild-type LRRK2, the protein is not apparent on microtubules, Villa noted. However, when wild-type LRRK2 is overexpressed, it forms filaments on microtubules. In addition, five of the six most common PD mutationsI2020T, N1437H, R1441G, R1441C, and Y1699Cpromote LRRK2 filament formation.

All of these mutations supercharge kinase activity, which would compel the kinase into its closed shape. I2020T sits in the activation loop of the kinase domain, right after G2019S, the most common pathogenic LRRK2 mutation, and the other three are at the interface between the GTPase and the COR-B domain, where they would be positioned to alter communication between the kinase and GTPase (see image above). It seems that if you force LRRK2 into an active state, it binds microtubules, Villa said.

Open and Shut. In the open kinase conformation (left), the LRRK2 monomer fits poorly into the filament structure. With its kinase (orange) closed (right), it clicks into place. [Courtesy of Deniston et al., Nature.]

Reck-Petersons data suggest that microtubule binding could cause problems. Co-first author John Salogiannis combined LRRK2, microtubules, and the motor proteins kinesin and dynein in cell-free assays. The motor proteins normally walk along microtubules, ferrying cargo toward the strands plus and minus ends, respectively. However, even low nanomolar amounts of LRRK2 shortened the distance the motors were able to walk. At 25 nM LRRK2, the motors ground to a halt, unable to step over the helical LRRK2 strands in their path.

No one knows if this roadblock serves a purpose, but Leschziner noted that LRRK2 is known to phosphorylate a subset of Rab GTPases that adorn vesicles transported along microtubules by motor proteins. Possibly, transient binding of LRRK2 oligomers to microtubules could pause motors long enough for the kinase to phosphorylate Rabs and change what cargoes get transported.

What Could This Mean for Therapy?Questions about microtubule binding may be pertinent for PD therapy development. Type I kinase inhibitors trap the enzyme in its closed state, while keeping it inactive by preventing it from binding ATP. Do Type I LRRK2 inhibitors enhance microtubule binding? Deniston et al.s data suggest as much, at least in cell-free assays. The researchers added the Type I inhibitor MLi-2 to their assay along with LRRK2, and found that the inhibitor further hampered motor protein movement along microtubules. MLi-2 is a pharmaceutical tool, not a drug in development (Fell et al., 2015; Scott et al, 2017). Conversely, Type II inhibitors, including the Bcr-Abl kinase inhibitor GZD-824, which stabilize an open kinase conformation, freed the motors to move again.

Mark Cookson at the National Institute on Aging, Bethesda, Maryland, noted that this finding might help explain the apparent paradox that LRRK2 kinase inhibitors enhance the formation of filaments inside cells, just as pathogenic PD mutations do. This was particularly puzzling when considering that mutations in LRRK2 are gain-of-function, and we have thought of kinase inhibitors as potentially therapeutic, Cookson wrote (full comment below).

These data provide further insight into another potential pathological mechanism of LRRK2, and may explain some on-target toxicity of certain LRRK2 inhibitors, though more research is needed, Andrew Koemeter-Cox at the Michael J. Fox Foundation wrote to Alzforum (full comment below). Likewise, Alessi suggested investigating whether Type II inhibitors would have fewer side effects.

Denali Therapeutics has two LRRK2 inhibitors, DNL201and DNL151, in Phase 1 trials. They are both thought to be Type I. No one has yet developed LRRK2-selective Type II inhibitors, Alessi noted.

More Mysteries The scientists are pursuing other LRRK2 riddles. Leschziner and Reck-Peterson have set their sights on the structure of other mutants. Curiously, so far G2019S has not been shown to increase LRRK2 binding to microtubules in cells. Like other pathogenic PD mutations, it turns on the kinase. However, unlike them, G2019S does not increase Rab phosphorylation in cells. G2019S may contribute to disease in a different mechanistic way than the others, Leschziner suggested.

To probe LRRK2s physiological role, Villa will study endogenous LRRK2 in PD-relevant cell types, such as dopaminergic neurons and glia. In cells, the protein is more often found associated with membranes than microtubules. Does it assume a different shape when it binds membranes? Villa will recruit LRRK2 to membranes in cell culture, and combine cryoET with mass spectrometry to identify its structure and interaction partners.

Huaibin Cai at NIA believes that finding these interaction partners is crucial to deciphering what the protein does. Future studies will be needed to determine the signaling cascades that regulate the conformational changes of LRRK2 kinase domain in different subcellular compartments, as well as to identify any particular cargoes stopped and modified by LRRK2, he wrote to Alzforum (full comment below).Madolyn Bowman Rogers

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Molecular Structure of LRRK2 Gives Clues to Parkinson's - Alzforum

Cell Biology

Cell Imagers Market to Witness Huge Growth By 2027 | Top Manufacturers GE Healthcare, Sartorius AG, Thermo Fisher Scientific, Leica Microsystems,…

New Jersey, United States,- A recent report on Cell Imagers Market added by Verified Market Research provides a detailed analysis of the industry size, sales forecast, and geographic landscape related to this business line. Further, the report highlights key hurdles and latest growth trends which are accepted by leading players and are part of the competitive spectrum of this business.

The Cell Imagers market research report provides a comprehensive analysis of this business segment and provides essential insight into the factors influencing revenue generation as well as industry growth. Apart from the regulatory outlook, the document also includes a detailed assessment of the regional scope of the market. Further, the report includes detailed SWOT analysis and explains the driving factors of the market.

Global Cell Imagers Market is growing at a faster pace with substantial growth rates over the last few years and is estimated that the market will grow significantly in the forecasted period i.e. 2019 to 2026.

Additional information including limitations & challenges faced by new entrants and market players in tandem with their respective impact on the revenue generation of the companies is enumerated. The document scrutinizes the impact of COVID-19 pandemic on growth as well as future remuneration of the market.

The report covers extensive analysis of the key market players in the market, along with their business overview, expansion plans, and strategies. The key players studied in the report include:

The report provides valuable insights about the advancements of the Cell Imagers market and the approaches regarding the Cell Imagers market with analysis of each region. The report further talks about the dominant aspects of the market and explores each segment.

Other details specified in the Cell Imagers market report:

Global Cell Imagers Market, By Product

Equipment Consumables Software

Global Cell Imagers Market, By Application

Drug Discovery Developmental Biology Cell Biology Stem Cell Biology

Global Cell Imagers Market, By End User

Academic & Research Institutes Pharmaceutical & Biotechnology Companies Academic & Research Institutes

To understand the Cell Imagers market dynamics, the market is analyzed across major global regions and countries. Verified Market Research provides customized specific regional and country-wise analysis of the key geographical regions as follows:

North America:USA, Canada, Mexico

Latin America:Argentina, Chile, Brazil, Peru, and Rest of Latin America

Europe:UK, Germany, Spain, Italy, and Rest of EU

Asia-Pacific:India, China, Japan, South Korea, Australia, and Rest of APAC

Middle East & Africa:Saudi Arabia, South Africa, U.A.E., and Rest of MEA

Comprehensive assessment of all opportunities and risks in the Cell Imagers market.

This exclusive study addresses key questions for stakeholders in the Cell Imagers Market:

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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

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

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.

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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

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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Scientists Think They've Figured Out a Main Culprit of Inflammatory Bowel Disease - ScienceAlert

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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