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Neuroscience

What Makes Memories So Detailed and Enduring? Newly Discovered Mechanism of Learning – SciTechDaily

The tiny red dots are inhibitory nerve cells within the brains hippocampus. The optogenetic tool, shown in green, allows researchers to measure the strength of messages to other nerve cells, using flashes of light. Credit: Matt Udakis

In years to come, personal memories of the COVID-19 pandemic are likely to be etched in our minds with precision and clarity, distinct from other memories of 2020. The process which makes this possible has eluded scientists for many decades, but research led by the University of Bristol has made a breakthrough in understanding how memories can be so distinct and long-lasting without getting muddled up.

The study, published in Nature Communications, describes a newly discovered mechanism of learning in the brain shown to stabilize memories and reduce interference between them. Its findings also provide new insight into how humans form expectations and make accurate predictions about what could happen in future.

Memories are created when the connections between the nerve cells which send and receive signals from the brain are made stronger. This process has long been associated with changes to connections that excite neighboring nerve cells in the hippocampus, a region of the brain crucial for memory formation.

These excitatory connections must be balanced with inhibitory connections, which dampen nerve cell activity, for healthy brain function. The role of changes to inhibitory connection strength had not previously been considered and the researchers found that inhibitory connections between nerve cells, known as neurons, can similarly be strengthened.

Working together with computational neuroscientists at Imperial College London, the researchers showed how this allows the stabilization of memory representations.

Their findings uncover for the first time how two different types of inhibitory connections (from parvalbumin and somatostatin expressing neurons) can also vary and increase their strength, just like excitatory connections. Moreover, computational modeling demonstrated this inhibitory learning enables the hippocampus to stabilize changes to excitatory connection strength, which prevents interfering information from disrupting memories.

First author Dr. Matt Udakis, Research Associate at the School of Physiology, Pharmacology and Neuroscience, said: We were all really excited when we discovered these two types of inhibitory neurons could alter their connections and partake in learning.

It provides an explanation for what we all know to be true; that memories do not disappear as soon as we encounter a new experience. These new findings will help us understand why that is.

The computer modeling gave us important new insight into how inhibitory learning enables memories to be stable over time and not be susceptible to interference. Thats really important as it has previously been unclear how separate memories can remain precise and robust.

The research was funded by the UKRIs Biotechnology and Biological Sciences Research Council, which has awarded the teams further funding to develop this research and test their predictions from these findings by measuring the stability of memory representations.

Senior author Professor Jack Mellor, Professor in Neuroscience at the Centre for Synaptic Plasticity, said: Memories form the basis of our expectations about future events and enable us to make more accurate predictions. What the brain is constantly doing is matching our expectations to reality, finding out where mismatches occur, and using this information to determine what we need to learn.

We believe what we have discovered plays a crucial role in assessing how accurate our predictions are and therefore what is important new information. In the current climate, our ability to manage our expectations and make accurate predictions has never been more important.

This is also a great example of how research at the interface of two different disciplines can deliver exciting science with truly new insights. Memory researchers within Bristol Neuroscience form one of the largest communities of memory-focussed research in the UK spanning a broad range of expertise and approaches. It was a great opportunity to work together and start to answer these big questions, which neuroscientists have been grappling with for decades and have wide-reaching implications.

Reference: Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output by Matt Udakis, Victor Pedrosa, Sophie E. L. Chamberlain, Claudia Clopath and Jack R. Mellor, 2 September 2020, Nature Communications.DOI: 10.1038/s41467-020-18074-8

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What Makes Memories So Detailed and Enduring? Newly Discovered Mechanism of Learning - SciTechDaily

Neuroscience

Neurocrine Biosciences and Voyager Therapeutics Present New Long-Term Three-Year Data Demonstrating that One-Time Treatment with an Investigational…

DetailsCategory: DNA RNA and CellsPublished on Saturday, 12 September 2020 14:07Hits: 360

-- Data for Investigational Gene Therapy Treatment NBIb-1817 (VY-AADC) Presented at the MDS Virtual Congress 2020 --

- NBIb-1817 Treatment Showed Sustained Improvement in Motor Function, Including Greater "On" Time without Troublesome Dyskinesia and Reduction in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Scores, and Reduction in the Amount of Medications Up to Three Years in Patients with Parkinson's Disease

- 14 of 15 Patients Treated with NBIb-1817 Continued to Experience an Improvement in Disease Staging after Three Years, as Assessed by the Modified Hoehn & Yahr Scale

- Re-Initiation of Enrollment in Registrational RESTORE-1 Clinical Trial of NBIb-1817 Planned for Later this Year

SAN DIEGO, CA and CAMBRIDGE, MA, USA I September 11, 2020 I Neurocrine Biosciences, Inc. (Nasdaq: NBIX) and Voyager Therapeutics, Inc. (Nasdaq: VYGR) today announced data from PD-1101, a Phase Ib open-label, three-year efficacy and safety study, demonstrating that a one-time treatment with investigational gene therapy, NBIb-1817 (VY-AADC), showed sustained improvement in motor function including greater "On" time without troublesome dyskinesia, reduction in Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, and reduction in the amount of medications in patients with Parkinson's disease.In the PD-1101 study, NBIb-1817 reduced average "Off" time by up to -1.91 hours and improved average "On" time without troublesome dyskinesia by up to +2.23 hours in patients with advanced Parkinson's disease after three years across three cohorts. In addition, 14 out of 15 patients treated with NBIb-1817 continued to show an improvement in disease staging after three years, as assessed by the modified Hoehn & Yahr scale. These new data, along with two-year data from another open-label Phase Ib trial, PD-1102, were presented today at the MDS Virtual Congress 2020, September 1216, 2020 (www.mdscongress.org/Congress/Registration.htm).

In data from the three-year PD-1101 trial, the one-time treatment with NBIb-1817 showed sustained reduction in diary "Off" time by an average of -0.15 to -1.91 hours (baseline 4.28 to 4.93 hours) and improved diary "On" time without troublesome dyskinesia by an average of +0.26 to +2.23 hours (baseline 10.32 to 10.46 hours) across the cohorts as reported by 15 patients with advanced Parkinson's disease. NBIb-1817 also showed sustained improvement in motor function after three years, as measured by UPDRS Part III off medication scores, by -10.2 to -19.0 points (baseline 35.8 to 38.2 points) across the cohorts, per clinician assessment. Requirements for Parkinson's disease medications were also reduced in cohorts 2 and 3 (daily levodopa-equivalent dose reductions, average of -322.0 and -441.2 mg/day, respectively; baseline 1507.0 and 1477.0 mg/day, respectively). Two-year data from the PD-1102 trial for 7 patients showed that NBIb-1817 reduced diary "Off" time by an average of -3.2 hours and increased diary good "On" time by +2.1 hours (baselines 9.3 hours and 6.6 hours, respectively). In this study, NBIb-1817 showed sustained improvement in motor function after two years, with improved UPDRS Part III off medication scores of -12.0 points (baseline 34.4). Requirements for Parkinson's disease medications were also reduced (daily levodopa-equivalent dose reduction, average of -439.5 mg/day; baseline 1500.9 mg/day). Preliminary safety data from both studies suggest that NBIb-1817 was well-tolerated, with no study drug-related serious adverse events (SAEs) reported. The most common adverse events reported were headache, hypoesthesia, and musculoskeletal pain (PD-1101), and upper respiratory tract infection, headache, nausea, and depression (PD-1102).

"It is promising to see that after three years, a single administration of one-time investigational gene therapy treatment NBIb-1817 showed sustained reduction in 'Off' time, as well as improvement in 'On' time without troublesome dyskinesia and other measures of motor function in patients with Parkinson's disease," said Chad Christine, M.D., primary author, a lead investigator of the study and Professor of Neurology at the University of California, San Francisco (UCSF) Weill Institute for Neurosciences. "Parkinson's disease patients' motor function would be expected to worsen over three years, making these results very encouraging. The standard of care for advanced Parkinson's disease has not significantly changed in decades and it is our hope that NBIb-1817 has the potential to become the first gene therapy for Parkinson's disease."

Parkinson's disease is a chronic, progressive and debilitating neurodegenerative disorder that affects approximately one million people in the U.S. and six million people worldwide. It is characterized by a loss of dopamine from neuronal degeneration, with a concomitant loss of the aromatic L-amino acid decarboxylase (AADC) enzyme required to synthesize dopamine in the brain, leading to associated impairment in motor, neuropsychiatric, and autonomic functions.

"We are pleased that the results from these studies show that one-time treatment with investigational NBIb-1817 may help restore the brain's ability to convert levodopa into dopamine," said Eiry Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. "Our hope is that NBIb-1817 will help patients experience less 'Off' time and more 'On' time and improve motor symptom control. We plan to re-initiate enrollment in our registrational RESTORE-1 clinical trial with NBIb-1817 this year and look forward to further evaluating NBIb-1817 in patients with Parkinson's disease."

NBIb-1817 is an investigational recombinant adeno-associated viral serotype 2 vector encoding the gene for human AADC that is designed to help produce the AADC enzyme in brain cells where it can convert levodopa to dopamine.

"We are encouraged by the congruence of long-term data, including clinician- and patient-reported clinical outcomes in our clinical studies," said Omar Khwaja, M.D., Ph.D., Chief Medical Officer and Head of Research and Development at Voyager Therapeutics. "These results are promising and show that the approach has the potential to transform the treatment of Parkinson's disease, and help improve the lives of patients and their families."

Additional information about PD-1101 and PD-1102 will be available on demand for registered participants through October 1, 2020 on the MDS meeting website (www.mdscongress.org/Congress/Registration.htm).

About Parkinson's Disease and NBIb-1817 (VY-AADC) Parkinson's disease is a chronic, progressive and debilitating neurodegenerative disease that affects approximately one million people in the U.S. and six million people worldwide. It is characterized by a loss of dopamine and neuronal degeneration with a concomitant loss of the aromatic L-amino acid decarboxylase (AADC) enzyme required to synthesize dopamine in the brain, leading to associated impairment in motor, neuropsychiatric, and autonomic functions. Dopamine is a chemical "messenger" that is produced in the brain and is involved in the control of movement. It is made when AADC converts the chemical levodopa to dopamine. As Parkinson's disease progresses, there is less AADC enzyme in parts of the brain where levodopa is converted to dopamine.

NBIb-1817 is an investigational recombinant adeno-associated viral (AAV) serotype 2 vector encoding the gene for human AADC that is designed to help produce the AADC enzyme in brain cells where it can convert levodopa to dopamine. NBIb-1817 is administered into the brain using intraoperative monitoring with magnetic resonance imaging (MRI)-facilitated targeted delivery.

About the RESTORE-1 Clinical TrialPaused temporarily in April 2020 due to the COVID-19 pandemic, Neurocrine Biosciences and Voyager Therapeutics plan to re-initiate RESTORE-1, a Phase 2, randomized, placebo-surgery controlled, double-blinded, multi-center clinical trial, to evaluate the safety and efficacy of NBIb-1817 in patients who have been diagnosed with Parkinson's disease for at least four years and have at least three hours of "Off" time during the day as measured by a validated self-reported patient diary.

For more information about the RESTORE-1 clinical trial, including eligibility criteria, please visit clinicaltrials.gov and restore1study.com.

About the RESTORE-2 Clinical TrialPreparations are ongoing for the RESTORE-2 global registrational trial that will include clinical sites within and outside the U.S.

About Neurocrine Biosciences and Voyager Therapeutics Strategic CollaborationIn 2019, Neurocrine Biosciences and Voyager Therapeutics entered into a strategic collaboration focused on the development and commercialization of gene therapy programs, VY-AADC for Parkinson's disease and VY-FXN01 for Friedreich's ataxia, as well as rights to two programs to be determined. This collaboration combines Neurocrine Biosciences' expertise in neuroscience, drug development and commercialization with Voyager's innovative gene therapy programs targeting severe neurological diseases.

About Neurocrine BiosciencesNeurocrine Biosciences is a neuroscience-focused, biopharmaceutical company with 28 years of experience discovering and developing life-changing treatments for people with serious, challenging and under-addressed neurological, endocrine and psychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, Parkinson's disease, endometriosis* and uterine fibroids*, with three pivotal and five mid-stage clinical programs in multiple therapeutic areas. Headquartered in San Diego, Neurocrine Biosciences specializes in targeting and interrupting disease-causing mechanisms involving the interconnected pathways of the nervous and endocrine systems. For more information, visit neurocrine.com, and follow the company on LinkedIn. (*in collaboration with AbbVie)

About Voyager TherapeuticsVoyager Therapeutics is a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases. Voyager is committed to advancing the field of AAV gene therapy through innovation and investment in vector engineering and optimization, manufacturing, and dosing and delivery techniques. Voyager's wholly owned and partnered pipeline focuses on severe neurological diseases for which effective new therapies are needed, including Parkinson's disease, Huntington's disease, Friedreich's ataxia, and other severe neurological diseases. For more information on Voyager, please visit the company's website at http://www.voyagertherapeutics.com or follow @VoyagerTx on Twitter and LinkedIn.

SOURCE: Voyager Therapeutics

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Neurocrine Biosciences and Voyager Therapeutics Present New Long-Term Three-Year Data Demonstrating that One-Time Treatment with an Investigational...

Genetics

Viking genetics and robots working together at Alderston Mains – The Scottish Farmer

Owning a Jersey herd that produces 8100 litres at 5.75%BF and 4.01%P (780kg fat plus protein), can prove problematic knowing where to turn to continue improving performance. But for Andrew Hastie and his family at Alderston Mains near Haddington in East Lothian, the answer has come through a marriage of focussed management, high quality genetics and up-to-date milking technology.

Having experienced success through a combination of the Viking Jersey and robotic milking during a gradual switch over the last three years, the Hasties have decided to follow this process to its logical end. This year, they will add their final two Lely Astronaut A5 robots, bringing their total to six (2 x A4 and 4 x A5), and theyll complete the switch to using genetics exclusively from the Viking countries (Sweden, Finland and Denmark).

With a modest acceptance that the herds production is nearer the top than the bottom, Mr Hastie remarks: Were not really far ahead of the average when you go to Denmark.

And therein lies the overriding reason for the familys choice of genetics, which sees the Vikings gradually take over from all other bloodlines.

The farms foundations were laid in the 1950s when grandfather, David Hastie, started the herd with native UK Jerseys. Since that time, Andrew and his parents, Gordon and Vivian, and brother, David, have fine-tuned both the farm and the herd, to reach the exceptional performance of today.

Over that period, the farm has switched from a mixed enterprise to one thats purely focussed on dairy, with all grass and arable crops across its 400 acres now grown exclusively for the 360-head herd. With a target of increasing the herd to 430 head, the plan is to consolidate numbers at this level.

Weve always enjoyed the Jersey and found her to have robustness and some health benefits over the Holstein, says Mr Hastie. We operate a sort of hybrid system where we want high yields but like the cows to go outside for exercise and grazing even with the robots as we feel its good for their health and keeps our feed costs down in summer.

Close attention has always been paid to the type of genetics that will best meet the farms targets, which began in the earliest days of the herd.

My grandfather was an early adopter of artificial insemination; hed use the best bulls he could get from the USA, New Zealand and Denmark and we continued breeding this mixture for a long time, he said.

Around 15 years ago we dropped the New Zealand bulls, largely because their genetics is driven by milk solids weight-based contracts, which are not quite like our own.

The USA we felt was at the other extreme, and our experience was that the taller, leaner and more angular animals didnt live so long.

We feel the Viking breeding programme has the balance just right, with cows which look long-lasting and producing high quality milk. They are particularly suited to our contract with Grahams Family Dairy, where we need to produce at least 5% fat for the Gold Top range.

In some past summers we had been slightly short of butterfat but find the VikingGenetics bulls are helpful in boosting that.

Around 18 months ago the farm also switched to sexed dairy semen which is now used alongside Aberdeen Angus beef.

Also opting to introduce genomic testing for heifers, Mr Hastie says this is giving an early indication of genetic potential across a range of traits.

When you have a cow on the ground you have a good idea of how she should breed, he says. But with a heifer, all you have is the animals pedigree, so a genomic test adds accuracy for many different traits.

There are also traits on the VikingGenetics bar chart which you dont normally have, he adds. This includes hoof health and saved feed index, which are helping us to breed cows with better feet and more efficiency.

We only started genomic testing recently but plan to test all 200 of our heifer calves born each year, he says. This supplies a linear bar chart, just like youd have for a bull, and you can see straight away what you need to improve.

It also ranks the heifers on the Nordic Total Merit [NTM] index, which is not unlike the UKs PLI [Profitable Lifetime Index].

Also using VikMate, the VikingGenetics mating program, Mr Hastie is able to set his own targets and receive a best-choice mating for each animal in the herd.

He says: If I want to focus on a particular trait, I can change that myself when running the program. This could be for hoof health, stature, milk quality or any other trait.

In fact, were already seeing big improvements in feet and legs through corrective breeding and starting to see changes in other areas.

This includes reducing udder depth and strengthening udder support we think theyll remain higher for longer and making other changes to help robotic milking.

This has involved a change of mindset and were now looking to widen rear teat placement as well as lengthen teats something we didnt do in the past.

We have also moved away from selection for production, now keeping our focus on health and functional traits. We have found that the milk is there, even without looking for it, which allows us to focus improvement on other areas.

Also aiming to improve the herds management and efficiency, the next robots to be installed will help in this endeavour.

He says: Our sixth robot will be a grazing robot, which will be used exclusively by our late lactation cows. Theyll be in strawed yards in winter and graze in summer, only receiving concentrates while at grass, when theyre having no total mixed ration.

Im confident well maintain their yields and should manage body condition score better. I think it will save 1-2 per head each day in feed costs for the last 30-40 days of lactation.

Asked how the Viking-bred cattle have impacted profitability, he believes its too early to say with any precision.

In a few years, when nearly all the herd is Danish, Ill be able to tell you but all I can say now is that we are very pleased.

FARM facts

360 milking Jerseys rising to 430 in year-round calving system

Production at 8100 litres at 5.75%BF and 4.01%P (780kg fat plus ptn)

All breeding switched to VikingGenetics for longevity and milk quality

Four A4/A5 Lely robots, increasing to six, including one grazing robot

Sexed semen produces 200 Jersey heifers/year for replacements and sale

Genomic testing introduced for all Jersey heifer calves this year

TMR fed to all milking groups except late lactation, plus concentrates to yield

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Viking genetics and robots working together at Alderston Mains - The Scottish Farmer

Genetics

Biotechnology timeline: Humans have manipulated genes since the ‘dawn of civilization’ – Genetic Literacy Project

Historically, biotech has been primarily associated with food, addressing such issues as malnutrition and famine.

Today, biotechnology is most often associated with the development of drugs. But drugs are hardly the future of biotech. Weve entered the Fourth Industrial Revolution, and genetics are on a new level. Biotech is paving a way for a future open to imagination, and thats kind of scary.

The next ten years will surely prove exciting as artificial intelligence and biotechnology merge man and machine

Most of the biotech developments before the year 1800 can be termed as discoveries or developments. If we study all these developments, we can conclude that these inventions were based on common observations about nature.

The Second World War became a major impediment in scientific discoveries. After the end of the second world war some, very crucial discoveries were reported, which paved the path for modern biotechnology.

The origins of biotechnology culminate with the birth of genetic engineering.There were two key events that have come to be seen as scientific breakthroughs beginning the era that would unite genetics with biotechnology:One was the 1953 discovery of the structure of DNA, by Watson and Crick, and the other was the 1973 discovery by Cohen and Boyer of a recombinant DNA technique by which a section of DNA was cut from the plasmid of an E. coli bacterium and transferred into the DNA of another. Popularly referred to as genetic engineering, it came to be defined as the basis of new biotechnology.

A version of this article was originally published on Brian Colwells website as A Giant-Sized History of Biotechnology and has been republished here with permission from theauthor.

Brian Colwell is a technology futuristwith an investment thesis focused on disruptions in this next Industrial revolution. His research areas includeagricultural,biotechnology and artificial intelligence. Follow @BrianDColwellon Twitterand at his website.

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Biotechnology timeline: Humans have manipulated genes since the 'dawn of civilization' - Genetic Literacy Project

Cell Biology

Live Cell Imaging Market size, trends, global industry report to 2019-2025 made possible by top research firm – WhaTech

Global Live Cell Imaging Market Size, Share & Trends Analysis Report by Product (Instruments, Consumables, and Software & Services), By Application (Stem Cells, Drug Discovery, Cell Biology, and Others), By End-User (Pharmaceutical & Biotechnology Companies, Research Institutes, and Contract Research Organizations) and Forecast 2019-2025

The global market for live cell imaging is estimated to have a CAGR of around 8.7% during the forecast period. The market is mainly driven due to growing prevalence of cancer, increasing application of high content screening and cell culture in drug discovery.

Cancer is one of the fatal diseases increasing rapidly across the globe. Cancer involves the development of abnormal cells which spread on mammoth scale and have potential to destroy other normal cells.

Therefore, early diagnosis and on time replacement of affected cells plays a significant role in the treatment of cancer. Live cell imaging technology is being used widely in the form of models to investigate disease mechanism and to develop therapies.

The models based on live cell imaging technology generates biological information in order to facilitate medical solutions promising preclinical drugs. Across the globe, there is a rise in the cancer patients each year.

According to the WHO, cancer was considered to be the second leading cause of mortalities in the year 2018. It is also estimated that 1 out of 6 deaths was due to cancer, therefore growing cancer across the globe further propels the market growth.

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Segmental Outlook

The global live cell imaging market is segmented based on product, application and end-user. Based on the product, the market is further classified into instruments, consumables, and software & services.

The instruments segment is projected to have considerable share owing to the high application of microscopes in various live cell imaging and technological advancements in the live cell imaging instruments. Based on the application, the global live cell imaging market is further segmented into stem cells, drug discovery, cell biology, and others.

The stem cells application segment is projected to hold considerable growth during the forecast period owing to growing investment in the stem cell research activities. On the basis of end-user the market is further segregated into pharmaceutical & biotechnology companies, research institutes, and contract research organizations (CRO).

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Market Segmentation

Global Live Cell Imaging Market by Product

Global Live Cell Imaging Market by Application

Global Live Cell Imaging Market by End-User

Regional Analysis

North America

Europe

Asia-Pacific

Rest of the World

Company Profiles

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Live Cell Imaging Market size, trends, global industry report to 2019-2025 made possible by top research firm - WhaTech

Cell Biology

Dartmouth Professor Prachee Avasthi Wins National Award in Cell Biology – India New England

HANOVER, NHPrachee Avasthi, an associate professor of biochemistry and cell biology atthe Geisel School of Medicineand one of the medical schools newest faculty members, has received the 2020 Women in Cell Biology Junior Award for Excellence in Research from the American Society for Cell Biology (ASCB).

The prestigious award is given each year to a woman in an early stage of her career who is making exceptional scientific contributions to cell biology, is developing a strong independent research program, and exhibits the potential for continuing at a high level of scientific endeavor and leadership.

Established in 1961, the ASCB is an inclusive, international community of biologists studying the cell as the fundamental unit of life. Now with more than 9,000 members worldwide, the organization is dedicated to advancing scientific discovery, advocating sound research policies, improving education, promoting professional development, and increasing diversity in the scientific workforce. More than 30 past or current ASCB members have won Nobel Prizes in medicine or chemistry.

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Dartmouth Professor Prachee Avasthi Wins National Award in Cell Biology - India New England

Cell Biology

Magenta Therapeutics to Participate in Upcoming Healthcare Investor Conferences in September – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced that the company will participate in the following September investor conferences:

Live webcasts can be accessed on the Magenta Therapeutics website at https://investor.magentatx.com/events-and-presentations. The webcast replays will be available for 90 days following each event.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

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Magenta Therapeutics to Participate in Upcoming Healthcare Investor Conferences in September - Business Wire

Cell Biology

Russia published the results of its COVID-19 vaccine and they dont live up to the hype – The Next Web

President Vladimir Putin recently announced that a team of Russian scientists had developed a COVID-19 vaccine and that it had been approved for use by the regulators at least, in Russia.

However, the announcement caused consternation among scientists and clinicians in the rest of the world as human trials for the vaccine nicknamed Sputnik V had only started a couple of months before Putins announcement.

The results of the phase one and two human trials of this vaccine have just been published in The Lancet. So what have we learned?

First, lets look at what type of vaccine this is. The vaccine platform used in this study used adenoviruses. These common cold viruses, called Ad5 and Ad26, are made safe and are incapable of growing in the body. They only function to deliver the genetic code of one of the novel coronavirus proteins, called the spike protein, into a cell.

By injecting people with these modified adenoviruses, the immune system is stimulated to respond to the spike protein at the time of immunization, and hopefully to respond for many years in the future, if the immunized person is exposed to the COVID-causing coronavirus, known as SARS-CoV-2.

[Read: These tech trends defined 2020 so far, according to 5 founders]

The vaccine platform the Russians are using is not novel. Some of the leading COVID-19 vaccines use adenoviruses, including the Oxford University vaccine and an Ad26 vaccine developed by Johnson and Johnson. Following successful animal trials, both are now being tested in humans. CanSino Biologicals, a Chinese company, has also shown that its Ad5 vaccine is safe and induces immunity against the coronavirus in humans.

However, the Russian group has shown that their stable, freeze-dried preparation of the vaccine works to the same extent as their frozen liquid vaccine preparation. This is important for shipping and deploying a vaccine.

The Lancet paper outlines acceptable safety data, even with the high dose used. These safety results are not unexpected as the safety of several adenovirus-based vaccines for different diseases has been demonstrated in earlier research.

So its safe, at least in healthy people aged 18 to 60, but does it work does it protect against COVID-19?

The Russian group showed that their vaccine induces high levels of antibodies that can bind to the spike protein. But a more important measure is the level of antibodies that are functional. That is, can the antibodies prevent, or neutralize, infection of a virus into a cell?

The levels of neutralizing antibodies were quite low in this study, compared with other published vaccine trials. So too were the T cell responses (the other arm of the immune systems adaptive response).

One interpretation of this is that these vaccines do not induce good neutralizing protection. Alternatively, the methods used to measure these immune responses may not have been optimal. In the absence of international reference standards, we cant tell if this vaccine is better or worse compared with others.

Crucially, as with other COVID-19 vaccine clinical trials, we dont know if that level of neutralization is enough to protect from infection and how long these antibodies remain in the blood. The publication shows responses only up to one month after immunization. The ultimate question of whether these vaccinated people are protected against COVID-19 was not a focus of this paper.

Despite the positive results of the small phase one trial of the Sputnik V vaccine, it needs to be tested in a much larger group of people before it can be used on an entire population with confidence.

All vaccines need to be tested in large numbers of people, of different ages and ethnicities, in phase three clinical trials. Phase three trials are necessary to gain a high level of confidence that the vaccine protects against infection. They also help to tease out rare side effects that may not be evident in a small group of healthy volunteers. This final stage of testing is not one that can or should be left out.

Unfortunately, the Sputnik moniker highlights the politicization of earnest scientific and medical efforts to develop vaccines against COVID-19. This vaccine nationalism is a source of much concern for everyone in the vaccine field who understands the power of vaccines to eliminate the disease, but only when used with the acceptance of the population.

This article is republished from The Conversation by Anne Moore, Senior Lecturer in Biochemistry and Cell Biology, University College Cork under a Creative Commons license. Read the original article.

Read next: The UKs first EV-only service station set to open soon

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Russia published the results of its COVID-19 vaccine and they dont live up to the hype - The Next Web

Cell Biology

A Microbiology and Human Disease Professor’s Perspective on COVID-19 – The Journal

It appears as if much of the information about the novel coronavirus pandemic is muddled with political bias, unsubstantiated claims, limited amounts or improper usage of research and even conspiracy theories. One finds great difficulty deciding which information to trust, and from which sources. While it is important to be able to fact-check and discern these things on ones own, the likelihood of finding objective information with a high level of veracity increases in direct proportion to the scientific credentials of the source. The Journal staff reached out to Dr. Noah Reynolds, Assistant Professor in the Department of Biology at UIS, for his perspective on the matter.

UIS Journal: What is your .job description?

Noah Reynolds: I teach courses in cell biology, introductory biology, microbiology, and human disease. I also work with students in the research laboratory investigating microbial protein synthesis.

UIS Journal: Can you discuss how you helped with COVID-19 testing and mitigation efforts, [and] what that was like?

NR: I was asked by the Dean of the College of Liberal Arts and Sciences, Dr. Lemke, to provide input on safety and disinfecting protocols that were being assembled. It is nice to get to put some of your expertise to use for the safety of the university, even if just in a very small wayThis was one of the great things that was happening. There is a lot of expertise at the university and everyone was happy to help as much as they could.

UIS Journal: Microphysiologically speaking, how do people become infected with COVID-19?

NR: A protein located on the SARS-CoV-2 viral particle called the spike protein engages with a protein, known as ACE2, on host cells. The interaction between the spike protein and ACE2 begins the process of the virus entering into the host cell. It appears that the ACE2 protein is expressed highly on cells of the respiratory tract, cornea, and gastrointestinal tract. It is important to stress that other factors are known to be important for viral entry into cells and we are really just starting to understand how the infection takes place.

UIS Journal: I heard that, while antibodies may not last very long, people can stay protected anyway. How does COVID-19 immunity work, and why dont we need antibodies to stay protected?

NR: Antibodies are only one part of our bodys response that protects us from a pathogen. Our adaptive immune system also includes B-cells and T-cells. These cells can provide us with immunological memory, and a second exposure to the pathogen activates the memory response. This provides us with protection if we ever encounter a pathogen again.

UIS Journal: Is there anything you wish people knew about COVID-19, or anything relating to the pandemic?

NR: We dont know the long-term effect of COVID-19. We are just starting to learn about heart damage and neurological consequences but it will be years before we really understand the long-term health problems that could be associated with COVID-19.

As Dr. Reynolds stated, it is hard to know what the future will hold regarding the novel coronavirus. Each month seems to hold new or ever-changing information, one prime example being the efficacy and importance of mask-wearing. The best option is to fact-check all information, learn to distinguish between reputable and disreputable sources, think critically for oneself, stay updated on the legislation, follow the appropriate CDC and local guidelines, mitigate risk, and stay prepared.

Read more:
A Microbiology and Human Disease Professor's Perspective on COVID-19 - The Journal

Cell Biology

Dr. Ma on First- and Second-Generation BTK Inhibitors in B-Cell Malignancies – OncLive

Shuo Ma, MD, PhD, highlights ongoing research withBTK inhibitors in B-cell malignancies.

Shuo Ma, MD, PhD, associate professor of medicine (hematology and oncology), Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, highlights ongoing research withBTK inhibitors in B-cell malignancies.

Currently, the BTK inhibitorsibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa)have indications in chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrm macroglobulinemia,says Ma. Ibrutinib is a first-generation BTK inhibitor, whereas acalabrutinib and zanubrutinib are second-generation BTK inhibitors.

Ibrutinib inhibits the BTK enzyme, which is a critical component of B-cell biology, survival, and proliferation. However, ibrutinibaffects other tyrosine kinases, such as EGFR, Ma explains.

As a result, patients may experience off-target toxicities with ibrutinib, adds Ma.

Although head-to-head clinical trials are needed, acalabrutinib and zanubrutinib may elicit less toxicity compared with ibrutinib as the agents are more selective,Ma concludes.

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Dr. Ma on First- and Second-Generation BTK Inhibitors in B-Cell Malignancies - OncLive