More and more evidence is coming out that people with COVID-19 are suffering from cognitive effects, such as brain fog and fatigue.

And researchers are discovering why. The SARS-CoV-2 virus, like many viruses before it, is bad news for the brain. In a study published Dec.16 in Nature Neuroscience, researchers found that the spike protein, often depicted as the red arms of the virus, can cross the blood-brain barrier in mice.

This strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain.

The spike protein, often called the S1 protein, dictates which cells the virus can enter. Usually, the virus does the same thing as its binding protein, said lead author William A. Banks, a professor of medicine at the University of Washington School of Medicine and a Puget Sound Veterans Affairs Healthcare System physician and researcher. Banks said binding proteins like S1 usually by themselves cause damage as they detach from the virus and cause inflammation.

"The S1 protein likely causes the brain to release cytokines and inflammatory products," he said.

In science circles, the intense inflammation caused by the COVID-19 infection is called a cytokine storm. The immune system, upon seeing the virus and its proteins, overreacts in its attempt to kill the invading virus. The infected person is left with brain fog, fatigue and other cognitive issues.

Banks and his team saw this reaction with the HIV virus and wanted to see if the same was happening with SARS CoV-2.

Banks said the S1 protein in SARS-CoV2 and the gp 120 protein in HIV-1 function similarly. They are glycoproteins - proteins that have a lot of sugars on them, hallmarks of proteins that bind to other receptors. Both these proteins function as the arms and hand for their viruses by grabbing onto other receptors. Both cross the blood-brain barrier and S1, like gp120, is likely toxic to brain tissues.

"It was like dj vu," said Banks, who has done extensive work on HIV-1, gp120, and the blood-brain barrier.

The Banks' lab studies the blood-brain barrier in Alzheimer's, obesity, diabetes, and HIV. But they put their work on hold and all 15 people in the lab started their experiments on the S1 protein in April. They enlisted long-time collaborator Jacob Raber, a professor in the departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, and his teams at Oregon Health & Science University.

The study could explain many of the complications from COVID-19.

"We know that when you have the COVID infection you have trouble breathing and that's because there's infection in your lung, but an additional explanation is that the virus enters the respiratory centers of the brain and causes problems there as well," said Banks.

Raber said in their experiments transport of S1 was faster in the olfactory bulb and kidney of males than females. This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes.

As for people taking the virus lightly, Banks has a message:

"You do not want to mess with this virus," he said. "Many of the effects that the COVID virus has could be accentuated or perpetuated or even caused by virus getting in the brain and those effects could last for a very long time."

Reference: Rhea EM, Logsdon AF, Hansen KM, et al. The S1 protein of SARS-CoV-2 crosses the bloodbrain barrier in mice. Nat Neurosci. 2020. doi:10.1038/s41593-020-00771-8

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Neuroscience

How we talk to each other about the tough stuff – Axios

December 18, 2020 medical

2020 brought unprecedented challenges for millions of people, but how we talk about our distress, pain and problems can help us cope.

Why it matters: Conversation "partners help, collaborate and validate us as we try to put into words what in some ways are unspeakable difficulties," says Denise Solomon, who studies interpersonal communication at Penn State University.

The big picture: Some researchers are calling for neuroscientists and communication scientists to collaborate in studying our conversations to more precisely understand what happens in our brains when we interact and try to support one another.

How it works: Supportive conversations can relieve stress and improve our emotions.

But the content of a conversation is key.

How a conversation unfolds is important, too.

But it's important to listen because advice often isn't what people are looking for, says Amanda Holmstrom, who studies interpersonal communication at Michigan State University.

The flip side: There's a lot of pressure on the listener, but the teller plays an important role. "Disclosers have to be willing to tell their story and be receptive to the help even recognizing their experience may be so specific and extreme that no one else has ever experienced it," says Solomon.

One potential pitfall: Conversations can devolve into rumination and co-rumination. We can get stuck in these "cul-de-sacs," as Solomon describes them, and "never get past this mutual telling of our distress to where it is reflective and ultimately put into a broader perspective."

Context: Neuroscientists have long studied our social brains through the lens of empathy, morality and other processes often by looking at one brain's neural activity during different interactions.

What to watch: Holmstrom and her colleagues propose in a new paper that interpersonal communication scientists could benefit from neuroscience tools to look at the simultaneous brain activity of two people engaged in conversation.

The bottom line: "Collaboration is critical," says Frith. "We have vast amounts of data but not enough theory to understand it."

Neuroscience

Managing stress and anxiety at the holidays – Norton Healthcare

December 18, 2020 medical

Managing stress and anxiety at the holidays | Norton Healthcare Louisville, Ky. Bryan Davis, Psy.D., clinical health psychologist with Norton Neuroscience Institute, discusses some ways to manage feelings you experience around the holidays.

By: Norton Healthcare Posted: December 18, 2020

Holidays can be a joyful time but also a time to cause extra mental stress and anxiety. Bryan Davis, Psy.D., clinical health psychologist with Norton Neuroscience Institute, discusses some ways to manage feelings you experience around the holidays.

Educational, therapeutic, support and exercise programs free of charge. Patient navigators help patients and families to coordinate care, communication and connection with other Norton Healthcare and community resources.

Call (502) 559-3230

Link:
Managing stress and anxiety at the holidays - Norton Healthcare

Neuroscience

Tagging, recording and replaying neural activity | Stanford News – Stanford University News

December 18, 2020 medical

A new molecular probe from Stanford University could help reveal how our brains think and remember. This tool, called Fast Light and Calcium-Regulated Expression or FLiCRE (pronounced flicker), can be sent inside any cell to perform a variety of research tasks, including tagging, recording and controlling cellular functions.

Stanford researchers have developed and tested a new molecular probe, called Fast Light and Calcium-Regulated Expression or FLiCRE (pronounced flicker), which could help scientists map and control neural activity. (Image credit: Getty Images)

This work gets at a central goal of neuroscience: How do you find the system of neurons that underlie a thought or cognitive process? Neuroscientists have been wanting this type of tool for a long time, said Alice Ting, professor of genetics in the Stanford School of Medicine and of biology in the School of Humanities and sciences, whose team co-led this work with the lab of Stanford psychiatrist and bioengineer, Karl Deisseroth.

In proof-of-concept experiments, detailed in a paper published Dec. 11 in Cell, the researchers used FLiCRE to take a snapshot of neural activity associated with avoidance behavior in mice. By coupling the FLiCRE snapshot with RNA sequencing, they discovered that these activated neurons primarily belonged to a single cell type, which was inaccessible using genetic tools alone. They then used FLiCRE in combination with an opsin a protein for controlling neural activity with light developed by Deisseroth to reactivate those same neurons a day later, which led the mice to avoid entering a certain room. The brain region the researchers studied, called the nucleus accumbens, is thought to play an important role in human psychiatric diseases, including depression.

FLiCRE is made up of two chains of molecular components that respond to the presence of blue light and calcium. This light sensitivity allows the researchers to precisely control the timing of their experiments, and calcium is an almost-universal indicator of cell activity. To get FLiCRE inside a cell, the researchers package it, in two parts, within a harmless virus. One part of FLiCRE attaches to the cell membrane and contains a protein that can enter the cells nucleus and drive expression of whatever gene the researchers have selected. The other part of FLiCRE is responsible for freeing the protein under certain specific conditions, namely if the concentration of calcium is high and the cell is bathed in blue light.

Whereas existing tagging techniques require hours to activate, the FLiCRE tagging process takes just minutes. The researchers also designed FLiCRE so that they can use standard genetic sequencing to find the cells in which FLiCRE activated. This allows them to study tens of thousands of cells at once, while other techniques tend to require the analysis of multiple microscopic images that each contain hundreds of cells.

In one series of experiments, the researchers injected FLiCRE into cells in the nucleus accumbens and used an opsin to activate a neural pathway associated with avoidance behavior in the mice. Once the calcium in FLiCRE-containing cells spiked the cellular indication that the mouse is avoiding something the cells glowed a permanent red that was visible through a microscope. The researchers also sequenced the RNA of the cells to see which ones contained the fluorescent protein, producing a cell-by-cell record of neural activity.

One goal was to map how brain regions are connected to each other in living animals, which is a really hard problem, said Christina Kim, a postdoctoral scholar in genetics at Stanford and co-lead author of the paper. The beauty of FLiCRE is that we can pulse and activate neurons in one region and then record all of the connected downstream neurons. It is a really cool way to look at long-range brain activity connections.

In the next experiments, the researchers used the cellular activity map from the first experiments. They also adjusted FLiCRE so that the protein expressed the opsin protein, which can be controlled by orange light to alter neuronal activity. After activating FLiCRE in the cells, the researchers sent orange light through the fiber optic implant whenever the mice would enter a certain room. In response, the mice steered clear of that room, indicating that FLiCRE had indeed located cells in the brain that drive avoidant behavior.

The development and testing of FLiCRE combined chemistry, genetics, biology and neuroscience, and many specialties within those disciplines. As a result, the tool has a wide range of possible applications, including in cells outside the brain, the researchers say.

I moved to Stanford in 2016 with the hope of being able to carry out extremely interdisciplinary and collaborative projects such as this, said Ting. This project has been one of the most rewarding aspects of my move to Stanford seeing something this challenging and ambitious actually work out.

The researchers are now working on additional versions of FLiCRE, with a goal of streamlining the process. They are hoping to simplify its structure and also make it capable of working with other biochemical events, such as protein interactions or neurotransmitter release.

Mateo Snchez, a former postdoctoral scholar in the Ting lab, is also co-lead author of the paper. Additional authors are Paul Hoerbelt, Lief E. Fenno and Robert Malenka, the Pritzker Professor of Psychiatry and Behavioral Sciences, Director of the Nancy Pritzker Laboratory and Deputy Director of the Wu Tsai Neurosciences Institute. Deisseroth, is the D. H. Chen Professor, and a professor of bioengineering and of psychiatry and behavioral sciences; and a member of Stanford Bio-X and the Wu Tsai Neurosciences Institute. Ting is a member ofStanford Bio-X, the Maternal & Child Health Research Institute (MCHRI), theStanford Cancer Institute and the Wu Tsai Neurosciences Institute, and a faculty fellow ofStanford ChEM-H.

This research was funded by the Walter V. and Idun Berry Postdoctoral Fellowship Program, the EMBO long-term postdoctoral fellowship, the National Institute of Mental Health, Stanford Psychiatry, the Wu Tsai Neurosciences Institute, the National Institute on Drug Abuse, the Defense Advanced Research Projects Agency Neuro-FAST program, the NOMIS Foundation, the Wiegers Family Fund, the Nancy and James Grosfeld Foundation, the H. L. Snyder Medical Foundation, the Samuel and Betsy Reeves Fund, the Gatsby Foundation, the AE Foundation, the Fresenius Foundation and the Chan Zuckerberg Biohub.

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

Neuroscience

AB Science will host a live webcast on December 17, 2020 on masitinib results in Alzheimer’s Disease – GlobeNewswire

December 18, 2020 medical

AB SCIENCE WILL HOST A LIVE WEBCAST ON THURSDAY DECEMBER 17, 2020 ON MASITINIB RESULTS IN ALZHEIMERS DISEASE

Paris, December 16, 2020, 6pm CET

AB Science SA (NYSE Euronext FR0010557264 AB) will host a live webcast on December 17, 2020 with key opinion leaders to discuss recently reported results from the Phase 2B/3 masitinib trial in Alzheimers Disease.

The webcast will feature presentations by four Key Opinion Leaders:

AB Science, along with these key opinion leaders, will provide:

The presentation will be followed by a Q&A session with the key opinion leaders and management of AB Science.

Masitinib is a tyrosine kinase inhibitor designed to selectively target mast cells and macrophages, through inhibition of c-Kit, Lyn, Fyn, and MCSFR-1 kinases, which may have broad applicability in neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), multiple sclerosis and Alzheimers Disease.

On December 16th, AB Science announced that its Phase 2B/3 trial with oral masitinib met its predefined primary endpoint.

Dial-In & Webcast Information

Webcast date: Thursday, December 17, 2020. US: 11am-12pm EST; Europe 5pm-6pm CETNumber for the US: +1646722 4916Number for France: +33 1 70 71 01 59 International numbers (outside US and France): Numbers for other countries are listed on the webcast pageConference ID: 14544963#

Webcast connection page here

KOL Biographies

The following key opinion leaders will participate in the webcast:

Bruno Dubois Bruno Dubois is currently Professor of Neurology at the Neurological Institute of the Salptrire University Hospital at Paris, University Pierre et Marie Curie Paris VI. He is Director of the Behavioural Neurology Department and of the Dementia Research Center at the Hospital. He is also Director of the Research Unit Inserm U-610 of the ICM (Institut du Cerveau et de la Moelle Epinire) of the Hospital. He is coordinator of the National Reference Center on Rare Dementias and of the National Reference Center for young-onset Alzheimer patients. He is President of the Scientific Committee of France-Alzheimer and of IFRAD (International Fund Raising for Alzheimers disease), consultant for the Human Frontier Program and Expert of the French Agency of Drugs. He is a member of the European Alzheimer Disease Consortium (EADC). He has published on anatomical and biochemical studies on the central cholinergic systems in rodents and humans; on cognitive neuropharmacology; and on neuropsychology in patients with dementia, with special reference to memory and executive functions. He recently organized an Expert Consensus on the new criteria for Alzheimers disease and a Task Force on the new criteria for Parkinsons disease dementia. He is principal or co-investigator of a number of research programs focusing on AD, prodromal AD and dementia in Parkinsons disease.

Philip ScheltensPhilip Scheltens, MD, PhD is Professor of Cognitive Neurology and Director of the Alzheimer Center at the VU University Medical Center in Amsterdam, as well as Honorary Professor of Neurology at University College London.From 2011-2015, he was the scientific director of the Dutch Pearlstring Institute (PSI). In 2013, he was appointed vice-chair of the board of the Dutch Deltaplan Dementie. Since 2015, he has been a member of the board of the Royal Academy of Sciences and Art. His main clinical and research interests are dementia in the broadest sense, from basic research to care and translational research. He is active in the field of biomarkers and clinical trials and has been the (inter) national PI for many studies, including Phase IIII multicentre clinical trials.He is founder of, and has directed since 2000, the VUmc Alzheimer Center in The Netherlands, and during this period, he has produced over 50 PhD theses. He also founded the Alzheimer Research Center, a center dedicated to and specialised in Alzheimer clinical trials, where he is now a scientific adviser and member of the Board of Trustees.Dr. Scheltens is an active member of several societies, including the Dutch Society for Neurology, the AAN, the Alzheimer Imaging Consortium, the ISTAART Consortium, and the ECNP. He has been instrumental in organising several national and international conferences, including the Imaging Symposium attached to AAIC. He is member of the management board of the dementia panel of the EAN.He is co-editor-in-chief of Alzheimers Research & Therapy and acts as an ad hoc reviewer of scientific articles for all of the major journals. He has authored >730 peer reviewed papers and >50 book chapters. His current Hirsch factor is 117 (Google Scholar).

Jeffrey L. CummingsJeffrey L. Cummings, M.D., is Director of the Chamber-Grundy Center for Transformative Neuroscience at UNLV in Las Vegas. Dr. Cummings is principal investigator/ director of the National Institutes of Health/National Institute of General Medical Sciences-funded Center for Neurodegeneration and Translational Neuroscience.Dr. Cummings is a world-renowned Alzheimers researcher and leader of clinical trials. He has been recognized for his research and leadership contributions in the field of Alzheimers disease through the Henderson Award of the American Geriatrics Society (2006), the Ronald and Nancy Reagan Research Award of the National Alzheimers Association (2008) and the Lifetime Achievement Award of the Society for Behavioral and Cognitive Neurology (2017). In 2010, he was honored by the American Association of Geriatric Psychiatry with their Distinguished Scientist Award. He was featured in Gentlemens Quarterly (June 2009) as a Rockstar of Science. Dr. Cummings interests embrace clinical trials, developing new therapies for brain diseases and the interface of neuroscience and society.Dr. Cummings was formerly professor of neurology and psychiatry at the University of California, Los Angeles (UCLA), director of the Mary S. Easton Center for Alzheimers Disease Research at UCLA and director of the Deane F. Johnson Center for Neurotherapeutics at UCLA. He is past president of the Behavioral Neurology Society and of the American Neuropsychiatric Association. Dr. Cummings has authored or edited 39 books and published over 700 peer-reviewed papers.Dr. Cummings completed his neurology residency and a fellowship in behavioral neurology at Boston University, Boston. His U.S. training was followed by a research fellowship in neuropathology and neuropsychiatry at the National Hospital for Nervous Diseases, Queen Square, London.

Olivier Hermine, MD, PhDOlivier Hermine, MD, PhD is Professor of Hematology at Paris V-Ren Descartes University, Chief of adults Hematology staff at Hospital Necker (Paris), member of the French Acadmie des Sciences and author of over 700 international publications. Olivier Hermine is also co-founder of AB Science and Head of its scientific committee.

About masitinibMasitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases.

About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Companys lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, and inflammatory diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB).

Further information is available on AB Sciences website: http://www.ab-science.com.

Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance.

These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents filed by AB Science with the Autorit des Marchs Financiers (AMF), including those listed in the Chapter 4 "Risk Factors" of AB Science reference document filed with the AMF on November 22, 2016, under the number R. 16-078. AB Science disclaims any obligationor undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations.

For additional information, please contact:

AB ScienceFinancial Communication & Media Relations investors@ab-science.com

Media Relations USA

RooneyPartnersJeffrey Freedmanjfreedman@rooneyco.com

+1646432 0191

Media Relations France

NewCapArthur Rouillarouille@newcap.fr

+33 (0)1 44 71 00 15

Read the rest here:
AB Science will host a live webcast on December 17, 2020 on masitinib results in Alzheimer's Disease - GlobeNewswire

Neuroscience

AB Science communicates the results from phase 2B/3 study evaluating masitinib in Alzheimer’s disease – GlobeNewswire

December 18, 2020 medical

AB SCIENCE COMMUNICATES RESULTS FROM PHASE 2B/3 STUDY EVALUATING MASITINIB IN ALZHEIMERS DISEASE

Paris, December 18, 2020, 8.30am CET

AB Science SA (NYSE Euronext FR0010557264 AB) today communicates the results from phase 2B/3 study evaluating masitinib in Alzheimers disease, together with details on the mode of action of masitinib in Alzheimers disease.

The presentation is available on the companys website and is available here.

Highlights of this presentation are:

The mode of action of masitinib in Alzheimers disease (AD) is based on four targets, which may have a synergistic effect:

The following preclinical data are presented. Experiments in a transgenic mouse model of AD that were carried out by the ICM Brain Institute in Paris, demonstrated that masitinib could:

The masitinib clinical development program in Alzheimers disease is comprised of one proof of concept study (AB04024) [Piette, 2011] and a phase 2B/3 study (AB09004).

Masitinib is positioned in patients with mild and moderate dementia, with MMSE Score (Mini Mental State Examination) ranging from 12 to 25, which is a different positioning from other compounds.

There are currently four drugs used in the treatment of mild and moderate AD (donepezil, rivastigmine, galantamine and memantine) that were approved about 20 years ago. Masitinib was evaluated in add-on to this standard of care.

Study AB09004 was an international, randomized, placebo-controlled, phase 2B/3 study evaluating different doses of masitinib as a treatment of patients with confirmed mild to moderate Alzheimers disease. This study compared the efficacy and safety of masitinib relative to placebo after 24 weeks of treatment when administered as an add-on therapy to cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or Memantine.

Study AB09004 was comprised of two independent sub-studies testing two distinct dosing regimens; masitinib 4.5 mg/kg/day versus its own placebo control (n=358, randomization 1:1), and masitinib 6.0 mg/kg/day titrated dose versus its own placebo control (n=277, randomization 2:1).

The study was to be considered successful if a significant improvement was reached on either ADAS-Cog or ADCS-ADL at a 2.5% level of statistical significance.

Baseline characteristics were balanced. Study AB9004 results were the following:

A new patent was filed based on results from study AB09004, which would permit AB Science to retain exclusive rights on the use of masitinib in Alzheimers disease until 2041.

Bruno Dubois (MD, PhD), Professor of Neurology at the Neurological Institute of the Salptrire University Hospital at Paris in France and coordinating investigator of the study said: Study AB09004 was a well-designed phase 2b/3 as it compared masitinib on top of standard of care treatment versus the standard of care. These data are very encouraging and may provide new hope for patients with Alzheimers disease.

Philip Scheltens (MD, PhD), Professor of Cognitive Neurology and Director of the Alzheimer Center at the VU University Medical Center in Amsterdam said: Results from study AB09004 bring a novel mechanism of action, which is very interesting considering the need for effective treatment in AD. The positive results from this study provide a robust basis to initiate a phase 3 confirmatory study.

Jeffrey L. Cummings (M.D), Director of the Chamber-Grundy Center for Transformative Neuroscience at UNLV in Las Vegas said: The data from this study are promising and support the use of the dose 4.5 mg /kg/day of masitinib for the future confirmatory study. Based on the mechanism of action of masitinib targeting the innate immune system via mast cells and microglia, it should be possible to investigate the correlations between clinical endpoints and biomarkers of neuro-inflammation and neurodegeneration in the next study.

KOL Biographies

The following key opinion leaders participated in the webcast:

Philip ScheltensPhilip Scheltens, MD, PhD is Professor of Cognitive Neurology and Director of the Alzheimer Center at the VU University Medical Center in Amsterdam, as well as Honorary Professor of Neurology at University College London. From 2011-2015, he was the scientific director of the Dutch Pearlstring Institute (PSI). In 2013, he was appointed vice-chair of the board of the Dutch Deltaplan Dementie. Since 2015, he has been a member of the board of the Royal Academy of Sciences and Art. His main clinical and research interests are dementia in the broadest sense, from basic research to care and translational research. He is active in the field of biomarkers and clinical trials and has been the (inter) national PI for many studies, including Phase IIII multicentre clinical trials. He is founder of, and has directed since 2000, the VUmc Alzheimer Center in The Netherlands, and during this period, he has produced over 50 PhD theses. He also founded the Alzheimer Research Center, a center dedicated to and specialised in Alzheimer clinical trials, where he is now a scientific adviser and member of the Board of Trustees. Dr. Scheltens is an active member of several societies, including the Dutch Society for Neurology, the AAN, the Alzheimer Imaging Consortium, the ISTAART Consortium, and the ECNP. He has been instrumental in organising several national and international conferences, including the Imaging Symposium attached to AAIC. He is member of the management board of the dementia panel of the EAN. He is co-editor-in-chief of Alzheimers Research & Therapy and acts as an ad hoc reviewer of scientific articles for all of the major journals. He has authored >730 peer reviewed papers and >50 book chapters. His current Hirsch factor is 117 (Google Scholar).

Jeffrey L. CummingsJeffrey L. Cummings, M.D., is Director of the Chamber-Grundy Center for Transformative Neuroscience at UNLV in Las Vegas. Dr. Cummings is principal investigator/ director of the National Institutes of Health/National Institute of General Medical Sciences-funded Center for Neurodegeneration and Translational Neuroscience. Dr. Cummings is a world-renowned Alzheimers researcher and leader of clinical trials. He has been recognized for his research and leadership contributions in the field of Alzheimers disease through the Henderson Award of the American Geriatrics Society (2006), the Ronald and Nancy Reagan Research Award of the National Alzheimers Association (2008) and the Lifetime Achievement Award of the Society for Behavioral and Cognitive Neurology (2017). In 2010, he was honored by the American Association of Geriatric Psychiatry with their Distinguished Scientist Award. He was featured in Gentlemens Quarterly (June 2009) as a Rockstar of Science. Dr. Cummings interests embrace clinical trials, developing new therapies for brain diseases and the interface of neuroscience and society. Dr. Cummings was formerly professor of neurology and psychiatry at the University of California, Los Angeles (UCLA), director of the Mary S. Easton Center for Alzheimers Disease Research at UCLA and director of the Deane F. Johnson Center for Neurotherapeutics at UCLA. He is past president of the Behavioral Neurology Society and of the American Neuropsychiatric Association. Dr. Cummings has authored or edited 39 books and published over 700 peer-reviewed papers. Dr. Cummings completed his neurology residency and a fellowship in behavioral neurology at Boston University, Boston. His U.S. training was followed by a research fellowship in neuropathology and neuropsychiatry at the National Hospital for Nervous Diseases, Queen Square, London.

Further information is available on AB Sciences website: http://www.ab-science.com.

For additional information, please contact:

AB ScienceFinancial Communication & Media Relations investors@ab-science.com

Media Relations USA

RooneyPartnersJeffrey Freedmanjfreedman@rooneyco.com

+1646432 0191

Media Relations France

NewCapArthur Rouillarouille@newcap.fr

+33 (0)1 44 71 00 15

Cell Biology

Cell Biology – Organelles, Cycles and Division, Signaling …

December 18, 2020 medical

Organelles, Cycles and Division, Signaling & Techniques

As a sub-discipline of biology, cell biology isconcerned with the study of the structure and function of cells. As such, itcan explain the structure of different types of cells, types of cellcomponents, the metabolic processes of a cell, cell life cycle and signalingpathways to name a few. Here, we shall look at some of the major areas of cellbiology including some of the tools used.

Cell Theory is a basic principle in biologythat was formulated by Thodor Schwann, Matthias Schleiden and Rudolph Virchow.

According to the Cell Theory:

Recently, the theory was modified to include thefollowing ideas:

A cell is a basic unit of life. This simplymeans that a cell is the smallest unit of a living thing. While some organismsare only made up of a single cell (bacteria, yeast etc) others aremulticellular organisms made up of manycells.

While there is a clear difference between unicellular and multicellularorganisms, some organisms may transition from unicellular organisms tomulticellular organisms under certain conditions.

A good example of this isslime mold that tends to transition to a multicellular organism under stressfulconditions. However, they are simply described as being partiallymulticellular. Therefore, the cell is the basic building block of any given organism.

For a multicellular organism, cells are specialized, which means that they havedifferentiated to carry out given functions.

The following are examples of specializedcells:

Sperm Cells - Sperm cells serve to fertilize the female eggto form the embryo.

Red Blood Cells - Red cells contain aprotein molecule known as hemoglobin and serve to transport oxygen to all partsof the body and expel carbon dioxide from the body.

White Blood Cells - There are differenttypes of white blood cells that serve to protect the body from disease causingorganisms.

- Basophils, Lymphocytes, Neutrophils, Monocytes, Eosinophils

Cardiomyocytes - These are cardiac muscle cells that make upthe heart muscle.

Nerve Cells (neurons) - These are cells of thenervous system that transmit information to and from different parts of the body(information is transmitted as electric and chemical signals). See also Sensory Cells.

Any given cell will have three major components.

These include:

Cell Wall

The cell wall is a complex, highly organized structure that defines the shape of a plant cell (it is also found in bacteria, fungi, algae, and archaea). In addition to defining the shape of plant cells, a cell wall has a few other functions that include maintaining the structural integrity of a cell, acting as a line of defense against a variety of external factors as well as hosting various channels, pores and receptors that regulate various functions of a cell. As such, it is a multifunctional structure in plant cells that also contributes to plant growth.

See Plant Biology.

Cell Membrane

Also known as the plasma membrane, the cellmembrane is a bi-lipid membrane layer (it is a double membranous structure)that is also composed of proteins and carbohydrates. This fluid like structureencircles the cell thereby containing the contents of a cell.

It's alsoselectively permeable, which means that it only allows certain materials(nutrients and minerals etc) to pass through to sustain the cell. The cellmembrane also functions to protect the cell and ensure stability.

Nucleus

The nucleus may be described as the largestorganelle of a cell. The nucleus is itself surrounded by a double membrane(nuclear envelope) and contains genetic information (genes) making it thecontrol center of a cell. As such, it controls such activities cell metabolismand reproduction.

Cytoplasm

The cytoplasm is the fluid matrix (jelly-like)found inside the cell (outside the nucleus). Various types oforganelles and minerals (salts) are suspended in this constantly streamingfluid. Apart from containing all the cell organelles, the cytoplasm also helpsmaintain the shape of a cell.

Cell organelles may be described as cellsubunits specialized to carry out given functions within the cell. There aredifferent types of organelles in cells that carry out given functions.

Thefollowing are some of organelles that can be found in a cell (excluding thecell membrane, cytosol and nucleus which are mentioned above):

Mitochondria - The mitochondria are rod-shaped organellesand sites of ATP synthesis. The mitochondria is also surrounded by a doublemembrane (with the inner membrane being highly folded forming the cristae).

Thisorganelle is commonly referred to as a power- generator given that it convertsoxygen and nutrients in to a chemical energy known as ATP (adenosine triphosphate)which provides the energy required for various activities of the cell. Apartfrom being a site for ATP synthesis, the mitochondrion is also involved in theself-destruction of a cell in a process known as apoptosis.

Ribosomes - Found in the cytoplasm and the surface of the rough endoplasmicreticulum, ribosomes are composed of RNA and proteins. They may be described asthe "cell factories" given that they are responsible for the synthesisof protein molecules.

Lysosomes - These are sac-like structures that are surrounded by amembrane (a single membrane). Lysosomes contain digestive enzymes, which areresponsible for breaking down proteins, lipids and nucleic acids. In addition,lysosomes are also involved in the removal of waste molecules as well asrecycling of molecular subunits.

Golgi body - These are flattened structures in a cellresponsible for temporary storage of protein in the cell.

Vacuoles - Vacuoles are also enclosed by a membrane and function to storesuch material as food, water, minerals and waste products among others.

Some of the otherorganelles include:

Cell cycle refers to a sequence in activelydividing cells where the cells pass through several stages before ultimatelydividing.

The stages of cell cycle include:

At GI, the metabolic changes take placepreparing the cell for the division process. At a given point known as therestriction point, the cell is committed to cell division and moves to the nextphase.

S - The S phase involves DNA synthesis. It isduring this phase that the replication of genetic material starts with each ofthe chromosome having two chromatic sisters.

G2 - During this phase, there are metabolicchanges that assemble the necessary cytoplasmic materials for the mitosisprocess and splitting of the mother cell.

M - The M phase is where nuclear division takes placeand followed by the division of the cell.

For most animals, cells may divide by mitosis ormeiosis. While the two processes result in the production of new cells, they aredifferent and produce different daughter cells.

Mitosis is the type of cell division that occursin all somatic cells. These are the types of cells that make up the bodytissues (apart from gametes/sex cells). Therefore, the primary role of mitosisis growth and replacing worn out cells.

Essentially, mitosis results in diploid cellsfrom one cell. Here, the chromosome is copied followed by the separation of thecopies on different sides of the cell before the cell ultimately separates intotwo. In the end, each of the new cells has a copy of the chromosome.

See more on chromosomes.

Mitosis has 5 major phases, which include:

Interphase - Here, the DNA strand is replicated/copied toproduce what is known as a bivalent chromosome (consisting of two chromatids orDNA strands that are replicas of each other). During the interphase stage, thenew strand is attached to the original one at a point known as the centromere.

Prophase - This is the second stage of mitosis. Here, the bivalentchromosomes formed during interphase condense to form tight packages.

Metaphase - This is the third stage where each of the chromosome line upat the center of the cell. The nucleus membrane has already started dissolvingwith each of the mitotic spindles attaching themselves to each of thechromatids. Here, it appears as if the chromatids are being stretched towardseither pole of the cell.

Anaphase - During anaphase, the fourth stage of mitosis, the chromatidsthat had attached to the spindles are separated (the chromatids are separatedfrom their copies) and pulled to either side of the cell. This results in twogroups of monovalent chromosomes.

Telophase - At the end of anaphase, another stage starts where nuclearmembranes start to form around the two formed groups of chromosomes. Thespindle fibers that attached to the chromatids get disassembled. Here, thechromosomes also condense.

Eventually, the cytoplasm divides/splits with a cellmembrane forming on each of the two daughter cells. This process is known ascytokinesis. Each of the new cellshas 46 monovalent chromosomes and has identical genetic information as theother.

In mitosis, it's important that the samegenetic information is copied when forming new cells. This is because the chromosomeshave all the information concerning the function of the cell.

Successfulcopying of information on to the new cells ensures that the new cell functionsproperly. In the event that there is a problem, then the new cell will be unableto perform its function as it should be. This would result in complicationsdepending on the function of the cell.

Unlike mitosis, meiosis produces haploid cells.

Diploid - Two new daughter cells from the original cell with the samenumber of chromosomes.

Haploid - With meiosis (a reductive type of cell division) the resultingcells will have less number of chromosomes.

Stages

Meiosis is also different from mitosis in thatthere are two phases of cell division. These are meiosis I and meiosis II.

Prophase 1 - Here, the homologous chromosomes pair and exchangeDNA form recombinant chromosomes. This stage ends with the spindle fibersstarting to form to attach to the chromosomes.

Metaphase 1 - The bivalent chromosomes arranges double rowhaving attached to the spindlefibers.

Anaphase 1 - The homologous chromosomes (in each bivalent)are separated and move to opposite poles of the cell.

Telophase 1 - With the separation of the chromosomes, anuclear membrane starts to form around the two groups of the chromosomes. Thisis followed by cytokinesis where the cell splits to form two new cells. This isagain followed by meiosis II. Meiosis II follows the same process as meiosis I.However, this halves the number of chromosomes.

* Meiosis is an important process that results ingenetic diversity.

What are the differences between Meiosis and Mitosis?

All cells originate from a single cell (a singlefertilized egg). In cell differentiation, cells become specialized as the bodydevelops. Apart from the single original cell (the fertilized egg), stemcells are also unspecialized. However, under certain conditions, they candifferentiate to become specialized cells that serve a specific function(s).

Although the differentiated somatic cells are different in that they performdifferent functions, they contain the same genome. However, the different typesof cells only express some of these genes, which results in the differencesmorphological and physiologicalbetweenthem.

In cells, signal transductions involve thetransmission of molecular signals. This is particularly from the exterior ofthe cell to its interior for appropriate cell response. Signals (biochemicalchanges) may either come from the environment the cell is in or from othercells that trigger changes.

Cells have receptors on the surface of the cell,which receives the signal prompting a response. For a response to take place,the signal has to be transmitted across the cell membrane.

Some of the common intracellular messengersinclude:

Cell signaling is very important given that ithelps control and maintain the normal physiological processes in the body.Different signaling processes will result in varying responses including celldifferentiation, proliferation of cells as well as metabolism among others.

Cell biology is largely concerned with the study of the structure and functions of cells (morphological and physiological). For this reason, a number of techniques have to be employed.

Some of the main cell biology techniques include:

Cells and tissues can be cultured usingcomplex media. With cells and tissues from more complex organisms, the culturemedia has to be more complex so as to provide the same environment as theenvironment from which the cell/tissue was obtained.

As for the tissue, theculturing process also allows for single cells to be obtained from the tissuein question for more studies.

The culture process requires the following:

Cell culture is an important technique giventhat it allows for only a sample (cells or tissue) to be used to learn moreabout the cells without the need to use the organism as a whole. This alsogives scientists a great opportunity to study the cells under varyingconditions.

Cell atlas helps better understand the biology of tropical disease parasite – News-Medical.net

December 18, 2020 medical

The first cell atlas of an important life stage of Schistosoma mansoni, a parasitic worm that poses a risk to hundreds of millions of people each year, has been developed by researchers at the Wellcome Sanger Institute and their collaborators.

The study, published today (18 December 2020) in Nature Communications, identified 13 distinct cell types within the worm at the start of its development into a dangerous parasite, including new cell types in the nervous and muscular systems. The atlas provides an instruction manual for better understanding the biology of S. mansoni that will enable research into new vaccines and treatments.

S. mansoni has a complex life cycle that begins when larval forms of the parasite emerge from snails into rivers and lakes. These larvae then enter humans through the skin after contact with infested water. Once inside the body, the parasite begins what is known as the intra-mammalian stage of its life cycle, undergoing a series of developmental transitions as it matures to adulthood.

Adult worms live in human blood vessels and reproduce, releasing eggs that pass from the body into water to continue the life cycle. But some eggs remain trapped in the body, leading to the disease schistosomiasis.

Schistosomiasis is a debilitating long-term illness that can lead to the inability to work, organ damage and death. It affects hundreds of millions of people each year, primarily in sub-Saharan Africa, and is listed by the World Health Organization (WHO) as one of the most Neglected Tropical Diseases. Currently, only one drug is available to treat the disease, but this is inappropriate for use in very young children and there are fears that overreliance on a single treatment will allow the parasites to develop resistance to the drug.

Researchers have been looking at ways to find new drug targets, but until now there has been no high-resolution understanding of the parasite's biology.

This new study sought to map all of the cells in the first intra-mammalian stage of the parasite using single-cell technology, which identifies different cell types present in an organism or tissue.

The early-stage parasites were broken apart into individual cells that were characterized by single-cell RNA sequencing by scientists at the Wellcome Sanger Institute. The data were then analyzed to identify cell types according to the genes expressed by individual cells, and where in the body these cells were located.

The team identified 13 distinct cell types, including previously unknown cell types in the nervous system and parenchymal system. Individual fluorescent probes were made for genes specifically expressed by each cell type. Scientists at the Morgridge Institute for Research in the USA then used these probes to confirm the position of the discovered cells within whole parasites under the microscope.

Dr Carmen Diaz Soria, a first author of the study from the Wellcome Sanger Institute, said: "Though significant advances in our understanding of Schistosoma mansoni have been made in recent years, we have yet to identify targets leading to a viable vaccine. Single-cell RNA sequencing provides a whole new level of biological detail, including previously unidentified cell types, that will allow us to better understand each cell population in the parasite."

To identify new drug targets, researchers most often look for differences between a pathogen and its human host. However, S. mansoni is far closer to us in evolutionary terms than most major parasites, such as those that cause malaria. It is hoped that these findings will reveal areas of the parasite's genetic code that are sufficiently different from our own to be viable treatment targets.

Dr Jayhun Lee, a first author of the study from the Morgridge Institute for Research, Wisconsin USA, said: "We found genes in the muscular system of Schistosoma mansoni that might be specific to schistosomes. Because they are found in these parasites but not in humans, they are one possible treatment target identified by the study. The muscle allows the parasite to travel through our bodies, so if we were able to hinder that ability, we may be able to halt its life cycle before reproduction takes place."

The authors also shed light on the parenchymal tissue of S. mansoni, the 'filler' tissue that connects all the tissues of the parasite together. Previous studies had found it difficult to isolate parenchymal cells for analysis. The cell atlas found that some genes that are important for the parasite to digest food are also associated with the parenchymal tissue. Disrupting how the parasite feeds by targeting these cells could be another avenue for therapies.

Schistosomiasis is one of the most serious neglected parasitic diseases and gaining a deeper understanding of the parasite's biology will help to expose vulnerabilities that could one day be targeted by new treatments. We hope that this cell atlas for the first intra-mammalian stage of Schistosoma mansoni will provide researchers with valuable clues to help accelerate the development of new treatments and eliminate this parasite from the lives of hundreds of millions of affected people each year."

Dr Matt Berriman, Senior author, Wellcome Sanger Institute

Source:

Journal reference:

Soria, C.L.D., et al. (2020) Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni. Nature Communications. doi.org/10.1038/s41467-020-20092-5.

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Cell atlas helps better understand the biology of tropical disease parasite - News-Medical.net

Cell Biology

Glycostem and Ghent University sign license agreement on NK cell therapy technology | DNA RNA and Cells | News Channels – PipelineReview.com

December 18, 2020 medical

DetailsCategory: DNA RNA and CellsPublished on Friday, 18 December 2020 13:05Hits: 137

- New opportunities for the development of NK-antibody combination therapies

- Significant positive effect on production time of Glycostem's lead product oNKord, and future CAR-NK and TCR-NK therapies

OSS, The Netherlands I Dec. 17, 2020 I Glycostem Therapeutics B.V., a leading clinical-stage company focused on the development of therapeutic off-the-shelf Natural Killer (NK) cells, and Ghent University (UGent) have signed a license agreement for an innovative NK cell production technology. Ultimately, this agreement will bring significant benefit to targeted treatment of patients suffering from cancer. The agreement not only opens up new opportunities for development of NK-antibody combination therapies but also has significant positive impact on the production time of Glycostem's lead product oNKord and its second (CAR-NK) and third (TCR-NK) generation therapies viveNKTM.

"This license agreement offers new opportunities for more targeted treatment of cancer patients. By using UGent's technology we are able to increase the expression of CD16 receptors resulting in an increase of the NK-cell's activity and its antibody binding properties. When a patient's immunity is weak, administering NK-cells will boost the patient's immune system and increase the antibody's therapeutic effectiveness," explains Troels Jordansen, CEO at Glycostem.

Glycostem's NK-cell based therapies are manufactured in its in-house GMP licensed facility. "Ghent University's technology has the potential to almost halve the time needed for NK cell progenitor cells to differentiate into fully functional NK-cells. By incorporating this in our processes both our manufacturing time and cost-effectiveness will be affected very positively without negative effect on the potency of the NK cells. This is an important part of paving the way for further upscaling the production of our NK-cells," says Troels Jordansen.

"We are glad to see our research translated to a clinical setting as it is based on many years of fundamental research into NK cell biology," tells Prof. Georges Leclercq, head of the UGent research team and group leader in the Cancer Research Institute Ghent (CRIG). "We hope that with this collaboration, we can positively impact the lives of many patient's affected by difficult to treat cancers."

Dr. Dominic De Groote (UGent Business Development) further explains: "This partnership is the result of continuing efforts by Ghent University and Ghent University Hospital to become a leading academic and clinical center for cell-based therapies. This technology is part of our growing portfolio of oncology and Advanced Therapy Medicinal Products (ATMP) related assets that we are actively developing from the bench to the bedside through our translational platforms."

Taking cellular immunotherapy to the next level

Glycostem is focused on developing first, second and third generation cancer treatments based on NK-cells. This licensing deal will affect Glycostem's full portfolio. After a successful phase I study Glycostem initiated a first-of-its-kind pivotal trial in acute myeloid leukemia (AML) with in-house manufactured nonmodified NK cells (oNKord). Over the coming months, AML patients will receive this form of treatment as part of a phase I-IIa trial. A pivotal phase IIa trial for Multiple Myeloma (MM) patients is expected to start second half of 2021. This makes Glycostem one of the frontrunners in this promising field of cellular immunotherapy.

About Glycostem

Netherlands-based Glycostem Therapeutics BV, a clinical stage biotech company, develops allogeneic cellular immunotherapy to treat several types of cancer. By harnessing the power of stem cell-derived Natural Killer (NK) cells, Glycostem's products are a safe alternative to CAR-T-cells. Glycostem's lead product, oNKord, is manufactured from allogeneic raw material and is available off-the shelf. Thanks to its nine patent families, longstanding technical expertise and resources, as well as 'Orphan Drug Designation', Glycostem has secured a leadership position in the global NK-cell market.

oNKord is produced in a closed system (uNiKTM) in Glycostem's state-of-the-art and GMP (Good Manufacturing Practice) licensed production facility in the Netherlands, from which it can be distributed globally. The production technology includes ex vivo generation of high numbers of NK-cells with a high degree of purity for clinical applications. oNKord successfully passed phase I clinical trial (elderly and frail AML - Acute Myeloid Leukemia - patients), providing solid safety data and strong indication of clinical activity, including response on MRD (Minimal Residual Disease). Results indicate that oNKord may be safely infused in AML patients.

Glycostem is furthermore developing a range of CAR-NK and TCR-NK products in-house and in cooperation with global partners.

Glycostem Therapeutics BV http://www.glycostem.com

Foot note: "oNKord" is a registered trademark of Glycostem in the US and in Europe. Trademark registrations of "viveNK" and "uNiK" are pending.

About Ghent University

Ghent University (UGent) is a major Belgian university located in the heart of Europe. Our organization is dedicated to research and innovation with over 5,500 researchers active in a wide area of life, physical and social sciences. Strong partnerships with the Ghent University Hospital (1000+ beds), VIB, IMEC and global leaders in academia and pharma/biotech industry thrive life science innovation at our university and is part of the thriving Belgian biotech region. Our translational platforms such as CRIG (focus on cancer) and GATE (focus on advanced therapy medicinal products) facilitate to bring science to the patient.

Prof. Georges Leclercq has a longstanding and internationally recognized expertise in differentiation and function of NK cells. The recent focus of his research group is to reveal the role of several transcription factors in the differentiation of human hematopoietic stem cells into mature NK cells, and in the maintenance and function of these mature NK cells. The ultimate aim is to attribute to improved NK-based cancer immunotherapy.

Cancer Research Institute Ghent http://www.crig.ugent.be

SOURCE: Glycostem

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Glycostem and Ghent University sign license agreement on NK cell therapy technology | DNA RNA and Cells | News Channels - PipelineReview.com

Cell Biology

ONK Therapeutics Announces Three Exclusive Option License Agreements, Which Extend and Strengthen its Dual-Targeted NK Cell Therapy Pipeline | More…

December 18, 2020 medical

DetailsCategory: More NewsPublished on Friday, 18 December 2020 12:27Hits: 159

GALWAY, Ireland, & SAN DIEGO, CA, USA I December 17, 2020 I ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, today announced that it has secured three new exclusive option license agreements which strengthen its off-the-shelf, dual-targeted natural killer (NK) cell therapy platform and extend its pre-clinical pipeline to four programs across both hematological and solid tumors.

The first option agreement, with Cellerant Therapeutics, gives exclusive rights to a humanized CLEC12A scFv binder. CLEC12A is strongly expressed by blasts in the majority of AML patients. The option to license has enabled ONK to expand its pre-clinical product portfolio, launching a fourth program (ONKT104). This dual-targeted approach combines the CLEC12A CAR with a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting death receptor 4 (DR4).

While expressed on leukemic stem cells, CLEC12A is absent from normal hematopoietic stem cells and we thus expect that our dual-targeted NK cell therapy approach should enable safe targeting, with a reduced risk of prolonged aplasia in AML, said Prof Michael ODwyer MD, ONK Therapeutics co-founder, and CSO.

The second agreement in-licenses a humanized, tumor-specific antibody targeting an aberrantly glycosylated tumor-associated form of MUC1 (TA-MUC1) from Glycotope GmbH. Multiple solid tumor types express the mucin MUC1, including non-small cell lung cancer, breast cancer, and ovarian cancer. This antibody will be integrated into ONKs pre-clinical program ONKT103, for solid tumors.

Non-selective targeting of MUC1 could be problematic since the target is also expressed by healthy tissues, but ODwyer explains how ONKs dual-targeted approach can be used to address this. We have designed a CAR tailored to the glycosylation pattern distinct to tumor-associated MUC1 with specific recognition of the carbohydrate antigens Tn and T on MUC1, the expression of which is restricted to cancer cells. Glycotope has identified the glycosylation pattern as a way to unlock the potential of TA-MUC1 as a solid tumor target. ONK is thus set to bring the natural benefits of NK cells over T cells to bear on TA-MUC1, in a tumor-specific fashion, while also further boosting efficacy and countering resistance through the use of our TRAIL variant targeting DR5, he said.

ONKs unique platform approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TRAILv. The incorporation of these two humanized scFvs has the potential to minimize the risk of immunogenicity in the allogeneic setting.

ONK is also exploring several innovative strategies to improve the homing of NK cells. This is an important consideration as ex-vivo expansion can lead to changes in chemokine receptor expression. Through this new license agreement with the NIH, ONK plans to enforce the expression of CCR7, which is downregulated on NK cell expansion. This may improve the homing of NK cells to lymph nodes and is expected to be particularly useful for ONKs off-the-shelf CD19 program targeting B cell lymphoma, ONKT101, which is partnered with Avectas.

ONK is making rapid progress since it announced its most recent financing in October. Chris Nowers, ex Kite Pharma Head of Europe, who joined at that time as Chief Executive Officer, said: The recent American Society of Hematology meeting highlighted the NK cell therapy area as offering great hope as the next generation of advanced cell therapies. We believe our best-in-class off-the-shelf, dual-targeted NK cell therapy platform has the potential to improve performance and overcome some of the shortcomings seen with earlier approaches. These new licensing activities strengthen and expand our programs and illustrate our ambition and strategy to become a leader in this exciting field.

The company recently expanded its operations into the USA, moving into JLABS @ San Diego, Johnson & Johnson Innovations flagship facility, at the heart of San Diegos precision medicine and cell therapy cluster. This represents a second facility that complements its main R&D team and operations in Galway, Ireland. The companys recruitment drive across both facilities has been rapid and the company continues to expand its capability in key areas, including NK cell biology, construct design, gene editing, and process development.

-Ends-

ONK Therapeutics http://www.onktherapeutics.com ONK Therapeutics Ltd is an innovative cell therapy company dedicated to developing the next generation of off-the-shelf, dual-targeted NK cell therapies targeting solid and hematological cancers.

The company was founded in 2015, by Prof. ODwyer MD, of NUI Galway, an expert in translational multiple myeloma research, the tumor microenvironment, and exploitation of NK cells as cellular immunotherapy. Its core proprietary platform is based on a dual-targeted NK cell expressing both a chimeric antigen receptor (CAR) targeting a known tumor antigen and a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting the death receptor pathway (i.e. DR4 or DR5). This unique approach has the potential to enhance efficacy by addressing both intrinsic (e.g. CAR engagement of a tumor-specific antigen) and extrinsic (e.g. signaling through the death receptor pathway) apoptotic pathways and to reduce the susceptibility to possible target antigen escape through the engagement of tumor antigen-independent TRAILv.

Its pre-clinical pipeline comprises four programs;

In addition to the unique dual-targeted NK cell therapy platform, the company has a strong research focus on strategies to enhance homing and persistence, and overcome exhaustion, including the exploration of proprietary gene edits, such as the deletion of checkpoint inhibitory receptors in NK cells.

ONK Therapeutics is headquartered in the med-tech hub of Galway, Ireland, with a wholly-owned US subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

About Avectas - http://www.avectas.com Avectas is a cell engineering technology business that has developed a unique delivery platform, Solupore to enable the ex vivo manufacture of cell therapy products, which have high in-vivo functionality.

Glycotope http://www.glycotope.com Glycotope is a biotechnology company utilizing a proprietary technology platform to develop highly tumor-specific monoclonal antibodies called GlycoBodies. GlycoBodies bind to targets (GlycoTargets) tumor-specific carbohydrate structure dependent, enabling the development of highly-specific immunotherapies across a broad range of cancer indications. Glycotope has to date discovered in excess of 150 GlycoTargets with GlycoBodies against eight of these targets currently under development.

Each GlycoBody can be developed in an array of modalities with different modes of action providing a unique offering in the (immuno) oncology space. Currently, six clinical and pre-clinical programs based on the GlycoBody technology are under development by Glycotope or its licensing partners.

SOURCE: ONK Therapeutics

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Cell Biology – Organelles, Cycles and Division, Signaling …

Cell atlas helps better understand the biology of tropical disease parasite – News-Medical.net

Glycostem and Ghent University sign license agreement on NK cell therapy technology | DNA RNA and Cells | News Channels – PipelineReview.com

ONK Therapeutics Announces Three Exclusive Option License Agreements, Which Extend and Strengthen its Dual-Targeted NK Cell Therapy Pipeline | More…