Tom Hanks and his wife, Rita Wilson, were among the earliest celebrities to catch the novel coronavirus. In an interview at the beginning of July, Hanks described how differently COVID-19 had affected each of them in March.

My wife lost her sense of taste and smell, she had severe nausea, she had a much higher fever than I did. I just had crippling body aches, he said. I was very fatigued all the time and I couldnt concentrate on anything for more than about 12 minutes.

Why does COVID-19 present such different symptoms or none at all in different people?

Preexisting conditions can only be part of the story. Hanks is over 60 and is a Type 2 diabetic, putting him in a high-risk group. Nevertheless, he survived his brush with the virus with no pneumonia and apparently without any long-lasting effects. Knowing what causes variation in different patients could help physicians tailor their treatments to individual patients an approach known as precision medicine.

In recent years, a gene-centric approach to precision medicine has been promoted as the future of medicine. It underlies the massive effort funded by the U.S. National Institutes of Health to collect over a million DNA samples under the All of Us initiative that began in 2015.

But the imagined future did not include COVID-19. In the rush to find a COVID-19 vaccine and effective therapies, precision medicine has been insignificant. Why is this? And what are its potential contributions?

We are a physician geneticist and a philosopher of science who began a discussion about the promise and potential pitfalls of precision medicine before the arrival of COVID-19. If precision medicine is the future of medicine, then its application to pandemics generally, and COVID-19 in particular, may yet prove to be highly significant. But its role so far has been limited. Precision medicine must consider more than just genetics. It requires an integrative omic approach that must collect information from multiple sources beyond just genes and at scales ranging from molecules to society.

Inherited diseases such as sickle cell anemia and Tay-Sachs disease follow a predictable pattern. But such direct genetic causes are perhaps the exception rather than the rule when it comes to health outcomes. Some heritable conditions for instance, psoriasis or the many forms of cancer depend on complex combinations of genes, environmental and social factors whose individual contributions to the disease are difficult to isolate. At best, the presence of certain genes constitutes a risk factor in a population but does not fully determine the outcome for an individual person carrying those genes.

The situation becomes yet more complicated for infectious diseases.

Viruses and bacteria have their own genomes that interact in complex ways with the cells in the people they infect. The genome of SARS-CoV-2 underlying COVID-19 has been extensively sequenced. Its mutations are identified and traced worldwide, helping epidemiologists understand the spread of the virus. However, the interactions between SARS-CoV-2 RNA and human DNA, and the effect on people of the viruss mutations, remain unknown.

Tom Hanks and his wife caught the virus and recovered in a matter of weeks. Presumably each was infected over the course of a few minutes of exposure to another infected person, involving cellular mechanisms that operate on a timescale of milliseconds.

But the drama of their illness, and that of the many victims with far worse outcomes, is taking place in the context of a global pandemic that has already lasted months and may continue for years. People will need to adopt changes in their behavior for weeks or months at a time.

What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualized gene-targeted fixes. But, genes, behavior and social groups interact over multiple timescales.

To capture all the data needed for such an approach is beyond possibility in the current crisis. A nuanced approach to the COVID-19 pandemic will depend heavily on imprecise population level public health interventions: mask-wearing, social distancing and working from home. Nevertheless, there is an opportunity to begin gathering the kinds of data that would allow for a more comprehensive precision medicine approach one that is fully aware of the complex interactions between genomes and social behavior.

With unlimited resources, a precision medicine approach would begin by analyzing the genomes of a large group of people already known to be exposed to SARS-CoV-2 yet asymptomatic, along with a similar-sized group with identified risk factors who are dying from the disease or are severely ill.

An early study of this kind by Precisionlife Ltd data mined genetic samples of 976 known COVID-19 cases. Of these, 68 high-risk genes were identified as risk factors for poor COVID-19 outcomes, with 17 of them deemed likely to be good targets for drug developments. But, as with all such statistical approaches, the full spectrum of causes underlying their association with the disease is not something the analysis provides. Other studies of this kind are appearing with increasing frequency, but there is no certainty in such fast-moving areas of science. Disentangling all the relevant factors is a process that will take months to years.

To date, precision medicine has proven better suited to inherited diseases and to diseases such as cancer, involving mutations acquired during a persons lifetime, than to infectious diseases. There are examples where susceptibility to infection can be caused by malfunction of unique genes such as the family of inherited immune disorders known as agammaglobulinemia, but these are few and far between.

Many physicians assume that most diseases involve multiple genes and are thus not amenable to a precision approach. In the absence of the kind of information needed for a multi-omic approach, there is a clear challenge and opportunity for precision medicine here: If it is to be the future of medicine, in order to complement and expand our existing knowledge and approaches, it needs to shift from its gene-centric origins toward a broader view that includes variables like proteins and metabolites. It must consider the relationships between genes and their physical manifestations on scales that range from days to decades, and from molecules to the global society.

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How to use precision medicine to personalize COVID-19 treatment according to the patient's genes - The Conversation US

Dublin, Aug. 31, 2020 (GLOBE NEWSWIRE) -- The "RNA-interference (RNAi) Market - Growth, Trends, and Forecast (2020 - 2025)" report has been added to ResearchAndMarkets.com's offering.

The RNA-interference (RNAi) market is expected to witness a CAGR of 10.12% during the forecast period. Certain factors that are driving the market growth include the increasing number of applications in molecular diagnostics, particularly in cancer and improving synthetic delivery carriers and chemical modifications to RNA.

Cancer diagnosis and treatment is currently undergoing a shift with the incorporation of RNAi techniques in personalized medicine and molecular diagnostics. The availability of high throughput techniques for the identification of altered cellular molecules and metabolites allows the use of RNAi techniques in various cancer diagnosis and targeting approaches. For diagnostic purposes, small interfering RNAs (siRNA) or microRNAs (miRNA) can be utilized. The commercial availability of siRNAs to silence virtually any gene in the human genome is dramatically accelerating the pace of molecular diagnosis and biomedical research. Thus, increasing the application of RNAi in molecular diagnosis and its viability as a therapeutic technique is expected to drive the growth of the RNAi market during the forecast period.

However, in recent years, there has been a decline in FDA drug approval rates. Getting FDA approval for a new drug has become extremely challenging. It approved less than half the number of new drugs in 2016 (19 so far) when compared to 2015 (45 total) and 2014 (41 total). Hence, despite the large investments, there has been a decline in the number of innovative drugs manufactured. FDA explains manufacturing standards and other complying issues as the major reasons for this declining trend. This can impede the growth of the RNAi therapeutics, especially since the miRNAs and siRNAs fall into the relatively new field of genetic medicine, wherein they may require more intensified clinical trials. The highly extensive clinical trials effectively result in low approval rates of drugs. This would mean that the stringent guidelines will be a major restraint for the growth of the market.

Key Market Trends

Oncology is Expected to Hold Significant Market Share in the Therapeutics Type

According to the World Health Organization, cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer. The number of new cases is expected to rise by about 70% over the next two decades.

Recent advancements, such as the development of small interfering RNA (siRNA) tolerant to nucleases and the development of non-viral vectors, such as cationic liposomes and nanoparticles, can overcome this obstacle and facilitate the clinical use of RNAi-based therapeutics in the treatment of cancer.

Substantial pipeline for cancer therapies by companies and institutes such as Enzon Pharmaceuticals (Santaris Pharma), University of Texas, OncoGenex, Isarna Therapeutics, Astrazeneca (Ionis Pharmaceuticals), and INSYS Therapeutics, Inc. are expected to drive the market. In addition, many companies have invested in R&D for nanocarriers to deliver oligonucleotides for cancer treatment, which is expected to contribute to the oncology verticle.

North America Dominates the Market and Expected to do the Same in the Forecast Period

The U.S. has a number of RNAi therapeutics that are in developmental pipelines. A number of biotechnology companies have made considerably high investments for RNAi therapeutic development. Big pharmaceutical developers have entered into collaboration agreements or licensing deals with a number of smaller firms in an attempt to capitalize on the expected growth in revenue that this market can have over the forecast period. For instance, AstraZeneca's agreement with Ionis pharmaceuticals is one of the big deals that are investing heavily into RNA-interference technology

Key Topics Covered:

1 INTRODUCTION

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS4.1 Market Overview4.2 Market Drivers4.2.1 Increasing Number of Applications in Molecular Diagnostics, Particularly in Cancer4.2.2 Improving Synthetic Delivery Carriers and Chemical Modifications to RNA4.3 Market Restraints4.3.1 Stringent FDA Regulations and Changing Reimbursement Environment4.3.2 Unstable Potentially Immunogenic Nature of RNA4.4 Porter's Five Forces Analysis4.4.1 Threat of New Entrants4.4.2 Bargaining Power of Buyers/Consumers4.4.3 Bargaining Power of Suppliers4.4.4 Threat of Substitute Products4.4.5 Intensity of Competitive Rivalry

5 MARKET SEGMENTATION5.1 Application5.2 Geography

6 COMPETITIVE LANDSCAPE6.1 Company Profiles6.1.1 Alnylam Pharmaceuticals6.1.2 Arcturus Therapeutics6.1.3 Arrowhead6.1.4 Dicerna Pharmaceuticals6.1.5 Quark Pharmaceuticals Inc.6.1.6 Ionis Pharmaceuticals Inc.6.1.7 Merck & Co. Inc. (Sigma Aldrich)6.1.8 Silence Therapeutics PLC6.1.9 Qiagen NV6.1.10 Phio Pharmaceuticals Corp.6.1.11 Thermo Fisher Scientific Inc.

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

For more information about this report visit https://www.researchandmarkets.com/r/xkpql3

Story continues

About ResearchAndMarkets.comResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

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World RNAi Market 2020-2025: Oncology is Expected to Hold Significant Market Share in the Therapeutics Type Area - Yahoo Finance UK

Impact of New Tissue Stem Cell Counting Algorithms

BOSTON (PRWEB) September 01, 2020

Stem cell biotechnology company, Asymmetrex, has been counting tissue stem cells like those used for bone marrow and cord blood transplantation therapies for a few years now. Recently, the company announced the issue of patents for its first-in-kind technology both in the U.S. and the U.K. However, until last Friday, August 28, Asymmetrex had not reported in the peer-reviewed academic literature how it achieves this feat that had been pursued by many distinguished labs for more than six decades.

Now in a report published in a special issue of OBM Transplantation, a peer-review journal for transplantation medicine research, Asymmetrex completes its introduction of the new technology to the fields of stem cell science and stem cell medicine. The report is the second invited article published in a special issue focused on the Isolation and Characterization of Adult Therapeutic Cells.

The new report describes Asymmetrexs discovery of mathematical formulas, call algorithms, that can be used to determine the number of stem cells in complex tissue cell preparations, like experimental samples or patient treatments. The stem cell counting algorithms are specific for different types of tissue stem cells. So, the algorithms defined for blood stem cells are distinct from the algorithms for liver stem cells, or lung stem cells. Once an algorithm is defined by the Asymmetrex technology, it can be used repeatedly as a simple, rapid, and inexpensive test to determine the quantity and dosage of its specific tissue stem cell type.

Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D., anticipated the August publication of the new algorithms in a talk given earlier at the 6th Annual Perinatal Stem Cell Society Congress in March of this year. Then and now, he says that he believes, Now that the tissue stem cell counting algorithms are available, everything will change in stem cell science and medicine.

Prior to Asymmetrexs technology, there was no method for counting tissue stem cells in research, medicine, or for any other of their many uses. So, the impact of the stem cell counting algorithms in research and medicine is far-reaching. Such information is a game changer for accelerating progress in stem cell science and stem cell medicine, including improving treatments like gene therapy whose success depends on targeting tissue stem cells. There will also be tremendous gains in cell biomanufacturing, drug development, and environmental toxicology, all whose capabilities are currently limited by the lack of a facile means to quantify tissue stem cells.

To make the new counting technology readily accessible for evaluation by the greater academic, medical, and industrial stem cell communities, Asymmetrex provides free tissue stem cell counting on its company website.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. The companys U.S. and U.K. patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of effective use of human adult tissue stem cells for regenerative medicine and drug development. Asymmetrex markets the first technology for determination of the dose and quality of tissue stem cell preparations (the AlphaSTEM Test) for use in stem cell transplantation therapies and pre-clinical drug evaluations. Asymmetrex is a member company of the Advanced Regenerative Manufacturing Institute BioFabUSA and the Massachusetts Biotechnology Council.

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New Report Begins a New Era of Stem Cell Science and Medicine: Stem Cell Biotechnology Company Asymmetrex Tells How It Counts Therapeutic Tissue Stem...

GAITHERSBURG, Md., Sept. 1, 2020 /PRNewswire/ --Cartesian Therapeutics, a fully integrated, clinical-stage biopharmaceutical company developing cell and gene therapies for cancer, autoimmune diseases and respiratory diseases, today announced that it has initiated a Phase 1/2 clinical trial of its lead RNA-engineered mesenchymal stem cell (MSC) therapy, Descartes-30, in patients with moderate-to-severe acute respiratory distress syndrome (ARDS), including that caused by COVID-19. Based upon the company's research and analysis, this program is understood to be the first RNA-engineered cell therapy to enter clinical development for ARDS and COVID-19. It is also the first cell therapy to specifically degrade NETs, webs of extracellular DNA and histones that entrap inflammatory cells, block alveoli and vessels, and drive the pathogenesis of ARDS and COVID-19.

"Patients with ARDS, especially those with COVID-19 ARDS, generate copious amounts of NETs that physically obstruct alveoli and vessels, which leads to respiratory distress, immune-mediated thrombosis and a vicious cycle of inflammation," said Bruce Levy, MD, Chief of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital and Parker B. Francis Professor at Harvard Medical School, and a clinical investigator in the Descartes-30 trial. "We would therefore expect that degrading NETs would improve oxygenation as well as resolve thrombi and quell inflammation in these patients. If successful, Descartes-30 would be a highly differentiated game-changer within our limited toolkit in managing this exceedingly difficult condition."

Descartes-30 is an off-the-shelf (allogeneic) MSC product engineered with Cartesian's RNA ArmorySM cell therapy platform. By expressing a unique combination of DNases that work synergistically, Descartes-30 can eliminate large, macroscopic amounts of NETs within minutes. MSCs are inherently immunomodulatory and naturally travel to the lungs, where they are expected to provide continuous, local delivery of DNases to NET-laden lung tissue.

"We engineered Descartes-30 without genomic modification, and therefore the production of DNases is expected to be time-limited to match the acute nature of ARDS," said Metin Kurtoglu, MD, PhD, Chief Medical Officer at Cartesian. "Given thatDescartes-30will produce DNases locally and transiently, we anticipate that it will have a favorable benefit-to-risk profile. We also anticipate that these properties will enable Descartes-30 to treat a wide array of NET-related autoimmune and cardiovascular diseases."

About the Phase 1/2a Clinical Trial

The "Phase 1/2a Study of Descartes-30 in Acute Respiratory Distress Syndrome" (NCT04524962) is enrolling patients with ARDS at multiple critical care units in the United States. Patients with ARDS due to COVID-19 are given enrollment priority. This first-in-human study aims to determine the safety and preliminary efficacy of Descartes-30 in patients with moderate to severe ARDS. The study, which is estimated to begin treatment in September, aims to enroll approximately 20 patients prior to initiation of a larger study. For more information visit http://www.cartesiantherapeutics.com/Descartes-30-ARDS.

About ARDS and NETs

ARDS is a severe inflammatory lung disease with a mortality of over 40%. Inflammation leads to injury of lung tissue and leakage of blood and plasma into air spaces, resulting in low oxygen levels and often requiring mechanical ventilation. Inflammation in the lung may lead to inflammation elsewhere, causing shock and injury or dysfunction in the kidneys, heart, and muscles. Some causes of ARDS include COVID-19, severe pneumonia (including influenza), sepsis, trauma, and smoke inhalation.

NETs are inflammatory webs of DNA and proteins produced by neutrophils. NETs are commonly found in ARDS and are thought to exacerbate the disease by physically occluding air spaces and vessels, leading to reduced oxygenation and increased risk of immune thrombi. NETs are implicated in a variety of conditions beyond ARDS, including autoimmune and cardiovascular diseases.

About the RNA ArmorySM

The RNA ArmorySM is Cartesian's proprietary RNA-based cell engineering platform that activates and arms cells with carefully selected, mRNA-based therapeutics. Unmodified donor cells enter the RNA ArmorySMin the millions; a battle-ready cell army leaves the RNA ArmorySMin the tens of billions. Each cell is equipped with a combination of therapeutics rationally chosen to have a synergistic effect on the disease. In the body, the cells deliver a precision-targeted treatment regimen directly to the site of disease. The cells express therapeutics with a defined half-life, enhancing their safety profile and making repeat dosing and outpatient administration possible. The platform is agnostic to cell type: we choose the best cell for the job, whether autologous or off-the shelf. For more information visithttps://www.cartesiantherapeutics.com/rna-armory/.

About Cartesian Therapeutics

Founded in 2016,Cartesianis a fully integrated, clinical-stage biopharmaceutical company developing potent yet safer cell and gene therapies designed to benefit the broadest range of patients with cancer, autoimmune and respiratory diseases. Cartesianhas three products in clinical development under four open investigational new drug application (INDs) with the U.S. Food & Drug Administration (FDA). All investigational therapies are manufactured at Cartesian's wholly owned, state-of-the-art cGMP manufacturing facility in Gaithersburg, MD.Cartesian's commanding IP position benefits in part from a broad, exclusive patent license from the National Cancer Institute. For more information visithttps://www.cartesiantherapeutics.com/clinical-trials/.

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Cartesian Therapeutics Initiates Clinical Trial of First RNA-Engineered Cell Therapy for Acute Respiratory Distress Syndrome and COVID-19 - BioSpace

It was about the 3rd week into Bastions recovery from his TPLO surgery and he was already having a rough time. Bastion was a gregarious yellow Labrador who had his injured stifle about 25 days ago. Fortunately, his family elected for him to have his stifle surgically reconstructed. Initially, he had recovered well from surgery. But one day in particular, he presented to the hospital because he had a brief setback. He was limping far more severely than what would be normally expected at this stage of recovery.

The osteotomy from his surgery had not yet completely healed and he was still in the middle of his prescribed 5 weeks of exercise strict restriction. His family was trying their best but Bastion wasnt having it. He was too active at home and his humans were growing frustrated. Anti-anxiety medications had been dispensed but they were not given. Instead, his family had decided to give him CBD oil at home. When I asked why the prescribed medications had not been given, the client responded, I found CBD oil at the local farmers market and I figured it would work just as well.

Like Bastion, an increasing number of pets are receiving cannabidiol (CBD) supplements. The popularity of CBD continues to rise and many clients are incorporating CBD as part of the medication protocol for their pets, either as an adjunct or, as alternative treatment option.

Perhaps the initial interest in the benefits of CBD can be traced back to 1998, or possibly earlier, when scientists at the National Institutes of Health discovered that CBD could protect cells from oxidative stress. These findings fueled interest in the human medical field and, in large part, that appeal has been transmuted into veterinary medicine. The regard for this molecule has risen to such levels that in many homes, CBD is being used as the sole treatment option for a variety of medical conditions.

Veterinarians are becoming more fluent in the fascinating pharmacology regarding the use of this phytocannabinoid. A recent survey indicated that most veterinarians (61.5%) felt comfortable discussing the use of CBD with their colleagues, but only 45.5% felt comfortable discussing this topic with clients.1 Furthermore, veterinarians and clients in states with legalized recreational marijuana were more likely to talk about the use of CBD products to treat canine ailments than those in other states.2 Lastly, CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures.1 At first glance, the use of CBD has tangential or limited relevance in the world of veterinary surgery. However, as one takes a closer look at the putative, and proven benefits, it is clear that we are just scratching the surface of its therapeutic benefits. This article takes a brief dive into the world of CBD and its promise in the field of veterinary surgery.

Pain

Whether you perform surgery within a specialty discipline (oncology, orthopedics, neurology, soft tissue surgery, mixed animal, oral/dental, etc), or surgery is only a small part of your general practice, every veterinarian endeavors to aggressively manage pain. The first choice for pain relief among many clinicians are the medications that have been more extensively studied including, but not limited to, anti-inflammatories, gabapentinoids, opioids, local anesthetics, and other analgesics (acetaminophen, amantadine, cerenia etc). These medications or a combination thereof, have been prescribed to treat pain from orthopedic surgery, soft tissue surgery, surgical neuropathic conditions, pain from intestinal surgery, to name just a few. In the most basic schema, pain is divided into four categories: nociceptive pain (a response to damaged tissue), neuropathic pain (a response to directly-damaged sensory or spinal nerves), centralized pain (the result of pain signals being improperly amplified), and inflammatory pain.1 Cannabinoids may have a role to play in mediating all four of these types of pain states. When tissue is damaged, histamine, serotonin, TNF-alpha, IL-1-beta, IL-6, and Il -17 6, and interleukin 17 are released.2 Cannabinoids bind to the CB1 receptors and attenuate the pain signal by slowing down the release of those neurotransmitters.3 This process can take place locally or in the central nervous system.3 Cannabinoids have also been shown to inhibit the release of GABA, a well known neurotransmitter associated with pain.3 Although there is a paucity of clinical research on the use of CBD to treat postoperative pain in the veterinary medical setting, there has been heartening research conducted in humans. Indeed, National Academies of Sciences, Engineering, and Medicine concluded that there is, substantial evidence that cannabis is an effective treatment for chronic pain in adults.

Opioids have long been the go to option, or cornerstone of pain management, however, the potential for the adverse events associated with the use of opioids in veterinary patients is universally accepted.38 I have seen how distressing it can be for a family to see their pet experiencing any of the unpleasurable side effects of opioids including urine retention, delayed bowel movements, whining, panting, disorientation, or other manifestations of dysphoria. Those are just some of the challenges that clinicians face when using opioids for chronic pain management. Considering the ongoing consequences of the opioid epidemic, there is a search for pain management solutions that are innovative, prone to less adverse events, and are more effective. As the scientific community begins to evaluate the evidence for use of CBD , it is clear that more research is needed.

Anecdotal reports of CBDs efficacy as a pain reliever are ubiquitous but more are turning to scientific data for evidence of CBDs efficacy. A study in 2020 evaluating effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients found that over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens.5 Almost all CBD users (94%) reported quality of life improvements.5 And in a recent study evaluating orally consumed cannabinoids for long-lasting relief of allodynia in a mouse model, found that cannabinoids reduced hyperalgesia and a similar effect was not found with morphine.4 Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine.4 The study demonstrated that cannabinoids provide long-term relief of chronic pain states.4 If research shows that use of cannabinoids in animals, specifically, CBD, can help to decrease the use of opioids for pain management, that would help make more animals comfortable and potentially help to fight the tragic epidemic of human prescription opioid abuse. Further research is needed in a variety of species, specifically, both the canine and feline species.

Bone Healing

Both general veterinary practitioners and veterinary surgeons commonly diagnose and treat fractures. A large retrospective study of fracture incidence in dogs in North America has not been published since 1994; however, the findings from that study are still informative regarding the frequency of bone injuries. That study demonstrated that approximately 24% of all patients in the population studied over a 10 year period were affected by a disorder of the musculoskeletal system, with fractures contributing the largest proportion (over 29%) of all of the diagnosis of the appendicular skeletal system.7 Although that research is dated, the conclusions from this study - at the very least, indicate that fractures are commonplace in the clinical veterinary setting.7 Fracture repair has gradually become more straightforward due to improvements in technology. Because of these innovations, speciality surgeons and general practitioners who repair fractures have begun to see better surgical outcomes. So whether you primarily stabilize fractures with implants, or if external coaptation of fractures with the intention to refer (or perhaps as the primary means of fixation) is your treatment of choice, all veterinary practitioners aim to help fractured bones heal quickly. Despite these technological improvements, bone healing can be protracted or non existent with some fractures. There are a variety of options at a veterinarians disposal to kick-start the healing process but perhaps in the near future, CBD may be added to that armamentarium. The effect of CBD in fracture healing has been investigated evaluating bone callus formation in femur fractures in a rat model.8 The findings demonstrated enhanced biomechanical properties of healing fractures in those given CBD compared with a control group.8 This effect was not found in those only given 9-THC. Moreover, the bone forming effects (osteogenic) of CBD were weakened when test subjects were given equal amounts of CBD and 9-THC.6 Another in vivo research study indicated that when CBD is incorporated into a surface that promotes bone growth (osteoconductive scaffold) it can stimulate stem cell migration and osteogenic differentiation.9 Further studies are needed to better evaluate the role of CBD in healing and bone metabolism of companion animals so that these findings can be applied in the clinical setting.

Additionally, cannabis has been shown to be a useful addition in treatment plans optimized to improve bone health in laboratory studies. A study endeavored to more closely understand the role of CB2 receptors in maintaining bone health. CB2 receptors in bone cells have been linked to maintaining bone density and stimulating growth, and may therefore have a part in reversing the effects of osteoporosis.10 One study evaluating role of CB2 receptors, found that in mice whose genes had been altered to remove the CB1 or CB2 receptors, those that developed signs of bone weakness that were far more pronounced than those in the control group.12 Another study in 2009, investigated the relationship between CB2 expression and bone disease in humans. The study found that people with dysfunctional CB2 receptors to have significantly weaker hand bones.11

Arthritis

Osteoarthritis (OA) affects many dogs, large and small. Most often, OA is the consequence of a developmental orthopedic disease that often affects a single joint or a pair of joints, and, less often, affects multiple joints. It is axiomatic that Mother Nature likes symmetry thus developmental orthopedic diseases frequently affect both left and right joints. For example, hip dysplasia is reportedly bilateral in >60% of affected dog,s13 and elbow dysplasia is bilateral in approximately 50% of affected dogs.14 Osteoarthritis occurs secondary to a myriad of primary orthopedic conditions that affect a variety of joints including: the hip (most common causes of OA in the hip: hip dysplasia, Perthes disease); stifle (patellar luxation, cranial cruciate ligament disease, osteochondritis dissecans [OCD]); elbow (elbow dysplasia, elbow OCD, fragmentation of the medial coronoid process, incomplete ossification of the humeral condyle); shoulder (shoulder OCD, developmental shoulder subluxation); tarsus (OCD of the talus), and carpus (carpal laxity, carpal subluxation secondary to chondrodystrophy); and metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joint degenerative osteoarthritis (digital osteoarthritis) .

Cannabinoids were found to treat pain secondary to inflammation in a variety of studies on humans. Some of the most compelling research has shown that cannabis can reduce the inflammation in the joint caused in human patients diagnosed with immune mediated arthritis.15 One study found that cannabinoids could simultaneously reduce the secretion of cytokines involved in inflammation from one type of TH immune cells, which were being under-produced, while also increasing their numbers to correct their scarcity.15 Furthermore in a study in 2003, researchers found that plant-based cannabinoids could suppress the expression of interleukin-1betaone of the most prominent markers for inflammation in patients with rheumatoid arthritisby as much as 50%.16 And finally, in 2006, transdermal applications of CBD were shown to decrease biomarkers that can contribute to neurogenic inflammation in a sample of arthritic rats. 17

A report published in the journal of PAIN, lead by researchers at Baylor College of Medicine revealed the results of a large, double blinded, placebo controlled study on the positive effects CBD had in the fight against osteoarthritis.18 The study was designed with two main goals: The first portion of the research studied the effect CBD had on the inflammatory molecules and cells in mice.18 The second portion of the study, investigated whether CBD improved the quality of life in dogs diagnosed with osteoarthritis. In lab tests and in mouse models, CBD significantly decreased the production of natural chemicals that promote inflammation and it increased the natural chemicals that fight inflammation.18 Essentially, what they saw was a drop in proinflammatory cytokines and an increase in anti-inflammatory cytokines. 18 For dogs with osteoarthritis, CBD significantly decreased pain and increased mobility in a dose-dependent fashion. Importantly, A lower dose of liposomal CBD was as effective as the highest dose of nonliposomal CBD, indicating that the effect of CBD was quicker and more effective when CBD was delivered encapsulated in liposomes than without.18 Blood samples indicated no significant harmful side effects, or adverse events, over the 4-week analysis period.18 Although this study is very promising and it supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain in dogs, it is important to consult with your pets veterinarian before giving any supplement or medication.

In the veterinary population, use of cannabidiol and other alternative treatments may have the potential to obviate the need for other medications, and thus spare patients from adverse effects associated with their use. More likely, the use of cannabinoids could be additive or synergistic in a multimodal treatment strategy and could increase quality-of-life issues associated with painful arthritic conditions.

Intervertebral Disk Disease

As our patients age, discs in the spine also undergo degenerative changes. Thus, degeneration of intervertebral discs is evitable. This process of degeneration is multifactorial process and it involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content.39 The magnitude and severity of disc degeneration can vary widely between patients. The most common locations of clinically relevant disc disease are located in the cervical spine, thoracolumbar spine, and the lumbosacral spine.40 Although there are various manifestations of disc disease, broad classifications of Hansen Type I and Type II are typically used to describe the condition. In short, disc material may either extrude (acute herniations) or protrude (chronic herniations), both of which compress the spinal cord which ultimately can cause pain, paresis, paralysis and other neurological deficits.40 The prevalence of thoracolumbar disc disease dogs has been estimated at 3.5%.40 Depending on the neurologic examination, diagnosis, severity, prognosis, and other factors, surgery may be recommended to decompress the spinal cord.

After surgical decompression, there are a host of challenges that the the patient, the family, and the surgeon, may have to work through including a potentially protracted recovery, recurrence of neurological signs, post surgical pain, spinal instability, urinary disorders, (cystitis, urinary tract infection, urinary retention, micturition disorders), ascending myelomalacia, and others.41 Could CBD play a part in helping to improve those affected by disc disease pre-, intra-, or post-operatively and what types of spinal disorders could benefit from CBD? A study conducted on the use of CBD in mice with degenerative disc disease showed promise in mitigating the effect of disc damage and wear.19 Instead of being ingested orally, CBD was injected at the site of the disc. Researchers investigated the effects of cannabidiol intradiscal injection using a combination of MRI and histological analyses.19 A puncture was created in the disc and then CBD was injected into the disc (30, 60 or 120 nmol) shortly after.19 The effects of intradiscal injection of cannabidiol were analyzed within 2 days by MRI.17 Fifteen days later, the group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses after the cannabidiol injection.19 What they found was that cannabidiol significantly decreased the effects of disc injury induced by the needle puncture.19 These results suggest that this compound could be useful in the treatment of intervertebral disc degeneration perhaps using a novel route of administration.

Unfortunately, the exact mechanism for how CBD oil helped protect disc damage is still being investigated. The hope is that the neuroprotective properties of cannabidiol can also be found in the study of canine and feline disc disease to ultimately improve functional recovery.

References:

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Silveira, J. W., Issy, A. C., Castania, V. A., Salmon, C. E. G., Nogueira-Barbosa, M. H., Guimares, et al. Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration. 2014. PLoS ONE 9:12 doi:10.1371/journal.pone.0113161

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Mateus M. Bergamaschi et al. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Nave Social Phobia Patients. Neuropsychopharmacology. 2011 36(6):1219-26 doi:10.1038/npp.2011.6.

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Palmieri B, Laurino C, Vadal M. A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars. Mar-Apr 2019;170(2):e93-e99. doi: 10.7417/CT.2019.2116.

Sangiovanni, E., Fumagalli, M., Pacchetti, B., Piazza, S., et al.. Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury. (2019). Phytotherapy Research. doi:10.1002/ptr.6400

B. Van Klingeren and M. Ten Ham. Antibacterial Activity of 9-tetrahydrocannabinol and Cannabidiol. 1976. 42(1-2): 9-12 doi:10.1007/bf00399444.

Giovanni Appendino et al. Antibacterial Cannabinoids From Cannabis Sativa: A StructureActivity Study. 2008. Journal of Natural Products 71(8):1427-430, doi:10.1021/np8002673

McIver, V., Tsang, A., Symonds, N., Perkins, N., et al. Effects of topical treatment of cannabidiol extract in a unique manuka factor 5 manuka honey carrier on second intention wound healing on equine distal limb wounds: a preliminary study. 2020. Australian Veterinary Journal. doi:10.1111/avj.12932

White, D. M., Mair, A. R., & Martinez-Taboada, F. Opioid-free anaesthesia in three dogs. Open Veterinary Journal. 2017 7(2), 104. doi:10.4314/ovj.v7i2.5

Hansen T, Smolders LA, Tryfonidou MA, et al: The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs. Vet Pathol 2017 Vol 54 (6) pp. 945-952.

40. Jeffery ND, Levine JM, Olby NJ, et al: Intervertebral disk degeneration in dogs: consequences, diagnosis, treatment, and future directions. J Vet Intern Med 2013 Vol 27 (6) pp. 1318-33.

41. Balducci F, Canal S, Contiero B, et al: Prevalence and Risk Factors for Presumptive Ascending/Descending Myelomalacia in Dogs after Thoracolumbar Intervertebral Disk Herniation. J Vet Intern Med 2017 Vol 31 (2) pp. 498-504.

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Unraveling the use of CBD in veterinary medicine - Jill Lopez

BURLINGAME, Calif.--(BUSINESS WIRE)--Humanigen, Inc., (HGEN) (Humanigen), announced today that the Company will host an investor call and webcast to discuss the case-control lenzilumab data in COVID-19 patients published this week in Mayo Clinic Proceedings, including a discussion with the infectious disease expert and lead author of the study, Dr. Zelalem Temesgen, Professor of Medicine at Mayo Clinic, and provide corporate updates.

Humanigen will host the conference call and webcast Thursday, September 3, 2020 at 11:00 a.m. EDT. All stakeholders are invited to attend.

To participate on the conference call, please dial toll free (833) 714-0938 or toll number (778) 560-2680. The conference ID number is 1158096. A simultaneous webcast of the call and presentation can be accessed by visiting: https://event.on24.com/wcc/r/2626581/3E36D8F5A4B03E3030E7A0D438AF9AA1.

In addition, a replay of the webcast will be available on the company website for 30 days following the event.

More details on Humanigens programs in COVID-19 can be found on the companys website at http://www.humanigen.com under the COVID-19 tab, and details of the US Phase III potential registration study can be found at clinicaltrials.gov using Identifier NCT04351152.

About Humanigen, Inc.

Humanigen, Inc. is developing its portfolio of clinical and pre-clinical therapies for the treatment of cancers and infectious diseases via its novel, cutting-edge GM-CSF neutralization and gene-knockout platforms. We believe that our GM-CSF neutralization and gene-editing platform technologies have the potential to reduce the inflammatory cascade associated with coronavirus infection. The companys immediate focus is to prevent or minimize the cytokine release syndrome that precedes severe lung dysfunction and ARDS in serious cases of SARS-CoV-2 infection. The company is also exploring the effectiveness of its GM-CSF neutralization technologies (either through the use of lenzilumab as a neutralizing antibody or through GM-CSF gene knockout) in combination with other CAR-T, bispecific or natural killer (NK) T cell engaging immunotherapy treatments to break the efficacy/toxicity linkage, including to prevent and/or treat graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, Humanigen and Kite, a Gilead Company, are evaluating lenzilumab in combination with Yescarta (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma in a clinical collaboration. For more information, visit http://www.humanigen.com.

Forward-Looking Statements

This release contains forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual events or results may differ materially from those contained in the forward-looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the various risks and uncertainties described in the "Risk Factors" sections and elsewhere in the Company's periodic and other filings with the Securities and Exchange Commission.

All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not place undue reliance on any forward-looking statements, which speak only as of the date of this release. We undertake no obligation to revise or update any forward-looking statements made in this press release to reflect events or circumstances after the date hereof or to reflect new information or the occurrence of unanticipated events, except as required by law.

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Humanigen to Host Investor KOL Conference Call - Business Wire

The approval of KYMRIAH, YESCARTA, Alofisel and Zyntelgo has increased the interest of pharma stakeholders in cell therapies; further, owing to the technical challenges in this field, outsourcing manufacturing operations has become a necessity

Roots Analysis has announced the addition of Cell Therapy Manufacturing Market (3rd Edition), 2019 2030 report to its list of offerings.

Owing to various reasons, the demand for cell therapies is anticipated to increase over the coming years. Therefore, both therapy developers and contract service providers may need to strengthen their capabilities and expand available capacity. In this context, automation is expected to be a key enabler within the cell therapy manufacturing and contract services industry.

To order this 500+ page report, which features 160+ figures and 250+ tables, please visit this link

More than 160 organizations claim to be engaged in cell therapy manufacturingThe market landscape is dominated by industry players, representing more than 60% of the total number of stakeholders. Amongst these, over 55 are large or mid-sized firms (having more than 50 employees).

100+ players focused on T-cell and stem cell therapiesMost of these players are focused on manufacturing T-cell therapies, including CART, TCR or TILs. It is worth highlighting that more than 35 organizations claim to have necessary capabilities for the manufacturing of both types of therapies.

Presently, 70+ companies have commercial scale capacityAs majority of the cell therapy products are in clinical trials, the demand is high at this scale. However, it is worth noting that several players (~50%) have already developed commercial scale capacity for cell therapies.

Europe is currently considered a current hub for cell therapy productionMore than 220 manufacturing facilities have been established by various players, worldwide; of these, 35% are in Europe, followed by those based in North America. Other emerging regions include Australia, China, Japan, Singapore, South Korea and Israel.

50+ facility expansions reported between 2015-2019More than 85% of the expansions are related to setting up of new facilities across different regions. Maximum expansion activity was observed in the US and in certain countries within the Asia Pacific regions.

20+ companies offer automated solutions to cell therapy developersPlayers that claim to offer consultancy services related to automation include (in alphabetical order) Berkeley Lights, Cesca Therapeutics, Ferrologix, FluDesign Sonics, GE Healthcare and Terumo BCT. Further, we identified players, namely (in alphabetical order) Fraunhofer Institute for Manufacturing Engineering and Automation IPA, Invetech, KMC Systems, Mayo Clinic Center for Regenerative Medicine and RoosterBio, that offer consultancy solutions related to automation.

Partnership activity has grown at an annualized rate of 16%, between 2014 and 2018More than 200 agreements have been inked in the last 5 years; majority of these were focused on the supply of cell-based therapy products for clinical trials. Other popular types of collaboration models include manufacturing process development agreements (16%), services agreements (12%) and acquisitions (10%).

By 2030, developed geographies will capture over 60% of the market shareAsia Pacific is anticipated to capture the major share (~36%) of the market by 2030. It is also important to highlight that financial resources, technical expertise and established infrastructure is likely to drive cell therapy manufacturing market in Europe, which is estimated to grow at a CAGR of ~26%.

To request a sample copy / brochure of this report, please visit this link

The USD 10+ billion (by 2030) financial opportunity within the cell therapy manufacturing market has been analyzed across the following segments:

The report features inputs from eminent industry stakeholders, according to whom the manufacturing of cell therapies is largely being outsourced due to exorbitant costs associated with the setting-up of in-house expertise. The report includes detailed transcripts of discussions held with the following experts:

The research covers profiles of key players (industry and non-industry) that offer manufacturing services for cell-based therapies, featuring a company overview, information on manufacturing facilities, and recent collaborations.

For additional details, please visithttps://www.rootsanalysis.com/reports/view_document/cell-therapy-manufacturing/285.html or email [emailprotected]

You may also be interested in the following titles:

Contact:Gaurav Chaudhary+1 (415) 800 3415+44 (122) 391 1091[emailprotected]

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Growing at an annualized rate of over 20%, the cell therapy manufacturing market is estimated to reach close to USD 10 Billion by 2030, claims Roots...

(CNN) Alzheimers disease and dementia are two diseases that many Americans are all too familiar with, but there is another dementia that plagued the late comedian Robin Williams.

It might be the most common disease youve never heard of, said Dr. James Galvin, a professor of neurology and director of the Lewy Body Dementia Research Center of Excellence at the University of Miamis Miller School of Medicine.

Williams had Lewy body dementia, which his family learned only after his death. Its often misdiagnosed as Alzheimers or Parkinsons disease due to its early similarity to those other neurodegenerative diseases.

That unfortunate misconception is one focus of Robins Wish, a documentary releasing September 1 about the final days of Williams, before he died by suicide in 2014.

Affecting about 1.4 million Americans, Lewy body dementias which include Lewy body dementia and Parkinsons disease dementia are the second most common form of dementia after Alzheimers disease, according to the Lewy Body Dementia Association.

Dementia is a disorder of mental processes characterized by memory disorders, personality changes and impaired reasoning due to brain disease or injury.

Lewy body dementia is associated with an accumulation of a protein called alpha-synuclein that builds up and deposits inside of cells and some classic areas in the brain, said Dr. Ford Vox, medical director of the Disorders of Consciousness Program at the Shepherd Center in Atlanta and a contributor for CNN. Parkinsons disease dementia, the other Lewy body dementia, starts as a movement disorder but progresses to include dementia and mood and behavioral changes.

When working properly, alpha-synuclein which is typically present in the brain and in small amounts in the heart, muscle and other tissues might play a role in regulating neurotransmitters. But when this protein aggregates and forms masses (called Lewy bodies) within the brain, the consequences are severe.

The most common symptoms of LBD include impaired thinking, fluctuations in attention, problems with movement, visual hallucinations, sleep disorders, behavioral and mood issues and changes in bodily functions such as the ability to control urinating.

Over time, people with LBD lose layer upon layer of that life that youve built, said Angela Taylor, the senior director of research and advocacy at the Lewy Body Dementia Association.

Thats what happened to Williams, who had been diagnosed with Parkinsons disease in 2013. It wasnt until his autopsy that his widow, Susan Schneider Williams, learned he actually had LBD. The film highlights how the disease devastated Williams health.

My husband had unknowingly been bottling a deadly disease, Schneider Williams said in the documentarys trailer. Nearly every region of his brain was under attack. He experienced himself disintegrating.

CNN founder Ted Turner is also battling the disease, as he revealed in a 2018 interview.

Experiences of dysfunction and ambiguity are common for many patients and their families. Here is what the disease really is, why its difficult to identify and how it damages peoples lives.

An elusive and insidious disease

The first published cases of Lewy body dementia occurred in the mid-1960s, but it took two decades for the disorder to be recognized by medical researchers.

In the 1980s, as the molecular understanding of Alzheimers improved, it became clear that a bunch of these people didnt seem to fit that (diagnosis), Galvin said.

For example, patients with LBD had visual hallucinations when most Alzheimers patients didnt. They also had more parkinsonism the signs and symptoms of Parkinsons disease, which include slowness, stiffness, tremors and imbalance than Alzheimers patients.

It wasnt until the mid-90s when a large group of people (the Dementia with Lewy Bodies Consortium) got together and coined the phrase dementia with Lewy bodies and started to write diagnostic criteria that could be applied, Galvin added. And that really changed the game because once you have criteria, then people can start to be better classified.

Aside from the association with Lewy bodies those abnormal accumulations of the protein alpha-synuclein in the brain the exact cause of LBD is unknown.

Potential, but rare, genetic factors include higher levels of mutations of certain enzymes and a family gene that might make someone predisposed to the disease.

Sorting through the symptoms

Some patients exhibit movement disorders that doctors first diagnose as Parkinsons disease. If those patients later develop dementia, they would then be diagnosed with Parkinsons disease dementia.

Others may begin with cognitive or memory disorders mistaken for Alzheimers disease. More specific changes in their cognitive function over time can lead to the diagnosis dementia with Lewy bodies.

Rarely will some individuals first show neuropsychiatric symptoms, which can include hallucinations, behavioral problems and difficulty with mental activities. When those appear simultaneously, that can prompt an initial diagnosis of LBD.

To specifically and accurately diagnose a person with LBD, doctors have to ask the right questions about his symptoms, Vox said.

Delusions for Alzheimers patients might occur late in the disease and be ill-formed, appearing as paranoia or mistrust such as thinking a spouse is cheating. For LBD patients, delusions happen earlier and are well-formed misidentifications, such as looking at a loved one and thinking she has been replaced by an identical impostor.

The more detailed the assessment, Galvin said, the easier it is to separate out the conditions.

Because Lewy body proteins cant be tested like Alzheimers proteins can, cases of LBD are often diagnosed during hospitalization for something else, Vox said. Or diagnosis can happen postmortem, when the family requests an autopsy for closure, to gain more context for any doubts or to donate the brain for research, Taylor said.

Transforming mental, cognitive and physical health

The symptoms may first hinder a persons ability to work, Taylor said. Then they can disrupt their ability to drive; manage their affairs and health; be socially active; dress themselves; and shower. A person might also become unable to control involuntary behaviors, Galvin said, resulting in constipation, drooling, low blood pressure or the inability to control urine or bowel movements.

A persons inability to visually perceive the spatial relationships of objects can lead to car accidents or injuries. People with LBD can experience anxiety, depression and REM sleep disorder in which people lose the muscle paralysis that normally occurs during deep stages of sleep and physically (and sometimes violently) act out their dreams. Once a person is finally diagnosed, the life expectancy is about four to five years, Vox said.

Theyre losing the essence of who they are slowly over time, Taylor said. Thats a journey that is a very difficult one.

Research to improve diagnoses and treatments is underway, but there are currently no treatments for Lewy body dementia specifically. Most patients are treated with medications for Alzheimers or Parkinsons disease, since the symptoms of LBD are similar. However, treating the various symptoms of LBD with medications not fine-tuned for the condition can be a real art and quickly fill up a patients medicine cabinet, Vox said.

You have to weigh costs-benefits of treating this versus that, or get double effects of this medication and a little bit of that as well, he said.

Newfound challenges for patients and familiesLewy body dementia can be a harrowing experience for both patients and their families.

Getting a diagnosis can be a matter of months- to yearslong doctor shopping, Galvin said.

Executive dysfunction can lead to behaviors that family members initially perceive as bad judgments. Delusions can make them frustrated and fearful.

As a caregiver, I think one of the challenges is recognizing that we cannot use the same skills and interpersonal dynamics that we came to rely on in our relationship with the person with LBD, Taylor said.

We have to develop new ones because you cannot reason with somebody who is having a hallucination or delusion. Sometimes you have to more step into their reality and empathize (and) learn a new way to offer assistance without them feeling like theyre being treated like a child.

Living with Lewy body disease

Its possible that the same healthy diet, sleep and exercise routines that have been found to mitigate symptoms of Alzheimers and Parkinsons diseases might also help people with LBD.

So exercise is very important in Lewy body dementia, too, Taylor said, because its biologically related to Parkinsons disease and shares a lot of the same symptoms.

For patients and families in need of support and guidance, the Lewy Body Dementia Association is equipped with such resources.

Nobody should face LBD alone, Taylor sasid. Not the person with LBD and not the family caregiver. This disease doesnt make anything really easy in life. And they shouldnt have to go through it without a guide and a support.

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Lewy body dementia: The life-changing disease that devastated Robin Williams - East Idaho News

A new study identifies a specific gene's previously unknown role in fertility. Analysing genetic data in people, the researchers found an association between mutations in this gene and early menopause. The study appears in the journal of Science Advances.

The human gene -- called nuclear envelope membrane protein 1 (NEMP1) -- is not widely studied. In animals, mutations in the equivalent gene had been linked to impaired eye development in frogs. When the gene is missing in fruit flies, roundworms, zebrafish and mice, the animals are infertile or lose their fertility unusually early but appear otherwise healthy. The researchers who made the new discovery were not trying to study fertility at all. Rather, they were using genetic techniques to find genes involved with eye development in the early embryos of fruit flies.

"We blocked some gene expression in fruit flies but found that their eyes were fine," said senior author Helen McNeill, PhD, the Larry J. Shapiro and Carol-Ann Uetake-Shapiro Professor and a BJC Investigator at the School of Medicine. "So, we started trying to figure out what other problems these animals might have. They appeared healthy, but to our surprise, it turned out they were completely sterile. We found they had substantially defective reproductive organs." Though it varied a bit by species, males and females both had fertility problems when missing this gene. And in females, the researchers found that the envelope that contains the egg's nucleus -- the vital compartment that holds half of an organism's chromosomes -- looked like a floppy balloon.

"This gene is expressed throughout the body, but we didn't see this floppy balloon structure in the nuclei of any other cells," said McNeill, also a professor of developmental biology. "That was a hint we'd stumbled across a gene that has a specific role in fertility. We saw the impact first in flies, but we knew the proteins are shared across species. With a group of wonderful collaborators, we also knocked this gene out in worms, zebrafish and mice. It's so exciting to see that this protein that is present in many cells throughout the body has such a specific role in fertility. It's not a huge leap to suspect it has a role in people as well." To study this floppy balloon-like nuclear envelope, the researchers used a technique called atomic force microscopy to poke a needle into the cells, first penetrating the outer membrane and then the nucleus's membrane. The amount of force required to penetrate the membranes gives scientists a measure of their stiffness. While the outer membrane was of normal stiffness, the nucleus's membrane was much softer.

"It's interesting to ask whether stiffness of the nuclear envelope of the egg is also important for fertility in people," McNeill said. "We know there are variants in this gene associated with early menopause. And when we studied this defect in mice, we see that their ovaries have lost the pool of egg cells that they're born with, which determines fertility over the lifespan. So, this finding provides a potential explanation for why women with mutations in this gene might have early menopause. When you lose your stock of eggs, you go into menopause." McNeill and her colleagues suspect that the nuclear envelope has to find a balance between being pliant enough to allow the chromosomes to align as they should for reproductive purposes but stiff enough to protect them from the ovary's stressful environment. With age, ovaries develop strands of collagen with the potential to create mechanical stress not present in embryonic ovaries.

"If you have a softer nucleus, maybe it can't handle that environment," McNeill said. "This could be the cue that triggers the death of eggs. We don't know yet, but we're planning studies to address this question." Over the course of these studies, McNeill said they found only one other problem with the mice missing this specific gene: They were anaemic, meaning they lacked red blood cells.

"Normal adult red blood cells lack a nucleus," McNeill said. "There's a stage when the nuclear envelope has to condense and get expelled from the young red blood cell as it develops in the bone marrow. The red blood cells in these mice aren't doing this properly and die at this stage. With a floppy nuclear envelope, we think young red blood cells are not surviving in another mechanically stressful situation." The researchers would like to investigate whether women with fertility problems have mutations in NEMP1. To help establish whether such a link is causal, they have developed human embryonic stem cells that, using CRISPR gene-editing technology, were given specific mutations in NEMP1 listed in genetic databases as associated with infertility.

"We can direct these stem cells to become eggs and see what effect these mutations have on the nuclear envelope," McNeill said. "It's possible there are perfectly healthy women walking around who lack the NEMP protein. If this proves to cause infertility, at the very least this knowledge could offer an explanation. If it turns out that women who lack NEMP are infertile, more research must be done before we could start asking if there are ways to fix these mutations -- restore NEMP, for example, or find some other way to support nuclear envelope stiffness." (ANI)

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Study reveals genetic mutations may be linked to infertility, early menopause - Devdiscourse

Efforts to use regenerative medicinewhich seeks to address ailments as diverse as birth defects, traumatic injury, aging, degenerative disease, and the disorganized growth of cancerwould be greatly aided by solving one fundamental puzzle: How do cellular collectives orchestrate the building of complex, three-dimensional structures?

While genomes predictably encode the proteins present in cells, a simple molecular parts list does not tell us enough about the anatomical layout or regenerative potential of the body that the cells will work to construct. Genomes are not a blueprint for anatomy, and genome editing is fundamentally limited by the fact that its very hard to infer which genes to tweak, and how, to achieve desired complex anatomical outcomes. Similarly, stem cells generate the building blocks of organs, but the ability to organize specific cell types into a working human hand or eye has been and will be beyond the grasp of direct manipulation for a very long time.

But researchers working in the fields of synthetic morphology and regenerative biophysics are beginning to understand the rules governing the plasticity of organ growth and repair. Rather than micromanaging tasks that are too complex to implement directly at the cellular or molecular level, what if we solved the mystery of how groups of cells cooperate to construct specific multicellular bodies during embryogenesis and regeneration? Perhaps then we could figure out how to motivate cell collectives to build whatever anatomical features we want.

New approaches now allow us to target the processes that implement anatomical decision-making without genetic engineering. In January, using such tools, crafted in my lab at Tufts Universitys Allen Discovery Center and by computer scientists in Josh Bongards lab at the University of Vermont, we were able to create novel living machines, artificial bodies with morphologies and behaviors completely different from the default anatomy of the frog species (Xenopus laevis) whose cells we used. These cells rebooted their multicellularity into a new form, without genomic changes. This represents an extremely exciting sandbox in which bioengineers can play, with the aim of decoding the logic of anatomical and behavioral control, as well as understanding the plasticity of cells and the relationship of genomes to anatomies.

Deciphering how an organism puts itself together is truly an interdisciplinary undertaking.

Deciphering how an organism puts itself together is truly an interdisciplinary undertaking. Resolving the whole picture will involve understanding not only the mechanisms by which cells operate, but also elucidating the computations that cells and groups of cells carry out to orchestrate tissue and organ construction on a whole-body scale. The next generation of advances in this area of research will emerge from the flow of ideas between computer scientists and biologists. Unlocking the full potential of regenerative medicine will require biology to take the journey computer science has already taken, from focusing on the hardwarethe proteins and biochemical pathways that carry out cellular operationsto the physiological software that enables networks of cells to acquire, store, and act on information about organ and indeed whole-body geometry.

In the computer world, this transition from rewiring hardware to reprogramming the information flow by changing the inputs gave rise to the information technology revolution. This shift of perspective could transform biology, allowing scientists to achieve the still-futuristic visions of regenerative medicine. An understanding of how independent, competent agents such as cells cooperate and compete toward robust outcomes, despite noise and changing environmental conditions, would also inform engineering. Swarm robotics, Internet of Things, and even the development of general artificial intelligence will all be enriched by the ability to read out and set the anatomical states toward which cell collectives build, because they share a fundamental underlying problem: how to control the emergent outcomes of systems composed of many interacting units or individuals.

Many types of embryos can regenerate entirely if cut in half, and some species are proficient regenerators as adults. Axolotls (Ambystoma mexicanum) regenerate their limbs, eyes, spinal cords, jaws, and portions of the brain throughout life. Planarian flatworms (class Turbellaria), meanwhile, can regrow absolutely any part of their body; when the animal is cut into pieces, each piece knows exactly whats missing and regenerates to be a perfect, tiny worm.

The remarkable thing is not simply that growth begins after wounding and that various cell types are generated, but that these bodies will grow and remodel until a correct anatomy is complete, and then they stop. How does the system identify the correct target morphology, orchestrate individual cell behaviors to get there, and determine when the job is done? How does it communicate this information to control underlying cell activities?

Several years ago, my lab found that Xenopus tadpoles with their facial organs experimentally mixed up into incorrect positions still have largely normal faces once theyve matured, as the organs move and remodel through unnatural paths. Last year, a colleague at Tufts came to a similar conclusion: the Xenopus genome does not encode a hardwired set of instructions for the movements of different organs during metamorphosis from tadpole to frog, but rather encodes molecular hardware that executes a kind of error minimization loop, comparing the current anatomy to the target frog morphology and working to progressively reduce the difference between them. Once a rough spatial specification of the layout is achieved, that triggers the cessation of further remodeling.

The deep puzzle of how competent agents such as cells work together to pursue goals such as building, remodeling, or repairing a complex organ to a predetermined spec is well illustrated by planaria. Despite having a mechanistic understanding of stem cell specification pathways and axial chemical gradients, scientists really dont know what determines the intricate shape and structure of the flatworms head. It is also unknown how planaria perfectly regenerate the same anatomy, even as their genomes have accrued mutations over eons of somatic inheritance. Because some species of planaria reproduce by fission and regeneration, any mutation that doesnt kill the neoblastthe adult stem cell that gives rise to cells that regenerate new tissueis propagated to the next generation. The worms incredibly messy genome shows evidence of this process, and cells in an individual planarian can have different numbers of chromosomes. Still, fragmented planaria regenerate their body shape with nearly 100 percent anatomical fidelity.

Permanent editingof the encoded target morphology without genomic editing reveals a new kind of epigenetics.

So how do cell groups encode the patterns they build, and how do they know to stop once a target anatomy is achieved? What would happen, for example, if neoblasts from a planarian species with a flat head were transplanted into a worm of a species with a round or triangular head that had the head amputated? Which shape would result from this heterogeneous mixture? To date, none of the high-resolution molecular genetic studies of planaria give any prediction for the results of this experiment, because so far they have all focused on the cellular hardware, not on the logic of the softwareimplemented by chemical, mechanical, and electrical signaling among cellsthat controls large-scale outcomes and enables remodeling to stop when a specific morphology has been achieved.

Understanding how cells and tissues make real-time anatomical decisions is central not only to achieving regenerative outcomes too complex for us to manage directly, but also to solving problems such as cancer. While the view of cancer as a genetic disorder still largely drives clinical approaches, recent literature supports a view of cancer as cells simply not being able to receive the physiological signals that maintain the normally tight controls of anatomical homeostasis. Cut off from these patterning cues, individual cells revert to their ancient unicellular lifestyle and treat the rest of the body as external environment, often to ruinous effect. If we understand the mechanisms that scale single-cell homeostatic setpoints into tissue- and organ-level anatomical goal states and the conditions under which the anatomical error reduction control loop breaks down, we may be able to provide stimuli to gain control of rogue cancer cells without either gene therapy or chemotherapy.

During morphogenesis, cells cooperate to reliably build anatomical structures. Many living systems remodel and regenerate tissues or organs despite considerable damagethat is, they progressively reduce deviations from specific target morphologies, and halt growth and remodeling when those morphologies are achieved. Evolution exploits three modalities to achieve such anatomical homeostasis: biochemical gradients, bioelectric circuits, and biophysical forces. These interact to enable the same large-scale form to arise despite significant perturbations.

N.R. FULLER, SAYO-ART, LLC

BIOCHEMICAL GRADIENTS

The best-known modality concerns diffusible intracellular and extracellular signaling molecules. Gene-regulatory circuits and gradients of biochemicals control cell proliferation, differentiation, and migration.

BIOELECTRIC CIRCUITS

The movement of ions across cell membranes, especially via voltage-gated ion channels and gap junctions, can establish bioelectric circuits that control large-scale resting potential patterns within and among groups of cells. These bioelectric patterns implement long-range coordination, feedback, and memory dynamics across cell fields. They underlie modular morphogenetic decision-making about organ shape and spatial layout by regulating the dynamic redistribution of morphogens and the expression of genes.

BIOMECHANICAL FORCES

Cytoskeletal, adhesion, and motor proteins inside and between cells generate physical forces that in turn control cell behavior. These forces result in large-scale strain fields, which enable cell sheets to move and deform as a coherent unit, and thus execute the folds and bends that shape complex organs.

The software of life, which exploits the laws of physics and computation, is enabled by chemical, mechanical, and electrical signaling across cellular networks. While the chemical and mechanical mechanisms of morphogenesis have long been appreciated by molecular and cell biologists, the role of electrical signaling has largely been overlooked. But the same reprogrammability of neural circuits in the brain that supports learning, memory, and behavioral plasticity applies to all cells, not just neurons. Indeed, bacterial colonies can communicate via ionic currents, with recent research revealing brain-like dynamics in which information is propagated across and stored in a kind of proto-body formed by bacterial biofilms. So it should really come as no surprise that bioelectric signaling is a highly tractable component of morphological outcomes in multicellular organisms.

A few years ago, we studied the electrical dynamics that normally set the size and borders of the nascent Xenopus brain, and built a computer model of this process to shed light on how a range of various brain defects arise from disruptions to this bioelectric signaling. Our model suggested that specific modifications with mRNA or small molecules could restore the endogenous bioelectric patterns back to their correct layout. By using our computational platform to select drugs to open existing ion channels in nascent neural tissue or even a remote body tissue, we were able to prevent and even reverse brain defects caused not only by chemical teratogenscompounds that disrupt embryonic developmentbut by mutations in key neurogenesis genes.

Similarly, we used optogenetics to stimulate electrical activity in various somatic cell types totrigger regeneration of an entire tadpole tailan appendage with spinal cord, muscle, and peripheral innervationand to normalize the behavior of cancer cells in tadpoles strongly expressing human oncogenes such as KRAS mutations. We used a similar approach to trigger posterior regions, such as the gut, to build an entire frog eye. In both the eye and tail cases, the information on how exactly to build these complex structures, and where all the cells should go, did not have to be specified by the experimenter; rather, they arose from the cells themselves. Such findings reveal how ion channel mutations result in numerous human developmental channelopathies, and provide a roadmap for how they may be treated by altering the bioelectric map that tells cells what to build.

We also recently found a striking example of such reprogrammable bioelectrical software in control of regeneration in planaria. In 2011, we discovered that an endogenous electric circuit establishes a pattern of depolarization and hyperpolarization in planarian fragments that regulate the orientation of the anterior-posterior axis to be rebuilt. Last year, we discovered that this circuit controls the gene expressionneeded to build a head or tail within six hours of amputation, and by using molecules that make cell membranes permeable to certain ions to depolarize or hyperpolarize cells, we induced fragments of such worms to give rise to a symmetrical two-headed form, despite their wildtype genomes. Even more shockingly, the worms continued to generate two-headed progeny in additional rounds of cutting with no further manipulation. In further experiments, we demonstrated that briefly reducing gap junction-mediated connectivity between adjacent cells in the bioelectric network that guides regeneration led worms to regenerate head and brain shapes appropriate to other worm species whose lineages split more than 100 million years ago.

My group has developed the use of voltage-sensitive dyes to visualize the bioelectric pattern memory that guides gene expression and cell behavior toward morphogenetic outcomes. Meanwhile, my Allen Center colleagues are using synthetic artificial electric tissues made of human cells and computer models of ion channel activity to understand how electrical dynamics across groups of non-neural cells can set up the voltage patterns that control downstream gene expression, distribution of morphogen molecules, and cell behaviors to orchestrate morphogenesis.

The emerging picture in this field is that anatomical software is highly modulara key property that computer scientists exploit as subroutines and that most likely contributes in large part to biological evolvability and evolutionary plasticity. A simple bioelectric state, whether produced endogenously during development or induced by an experimenter, triggers very complex redistributions of morphogens and gene expression cascades that are needed to build various anatomies. The information stored in the bodys bioelectric circuitscan be permanently rewritten once we understand the dynamics of the biophysical circuits that make the critical morphological decisions. This permanent editing of the encoded target morphology without genomic editing reveals a new kind of epigenetics, information that is stored in a medium other than DNA sequences and chromatin.

Recent work from our group and others has demonstrated that anatomical pattern memories can be rewritten by physiological stimuli and maintained indefinitely without genomic editing. For example, the bioelectric circuit that normally determines head number and location in regenerating planaria can be triggered by brief alterations of ion channel or gap junction activity to alter the animals body plan. Due to the circuits pattern memory, the animals remain in this altered state indefinitely without further stimulation, despite their wildtype genomes. In other words, the pattern to which the cells build after damage can be changed, leading to a target morphology distinct from the genetic default.

N.R. FULLER, SAYO-ART, LLC

First, we soaked a planarian in voltage-sensitive fluorescent dye to observe the bioelectrical pattern across the entire tissue. We then cut the animal to see how this pattern changes in each fragment as it begins to regenerate.

We then applied drugs or used RNA interference to target ion channels or gap junctions in individual cells and thus change the pattern of depolarization/hyperpolarization and cellular connectivity across the whole fragment.

As a result of the disruption of the bodys bioelectric circuits, the planarian regrows with two heads instead of one, or none at all.

When we re-cut the two-headed planarian in plain water, long after the initial drug has left the tissue, the new anatomy persists in subsequent rounds of regeneration.

Cells can clearly build structures that are different from their genomic-default anatomical outcomes. But are cells universal constructors? Could they make anything if only we knew how to motivate them to do it?

The most recent advances in the new field at the intersection of developmental biology and computer science are driven by synthetic living machines known as biobots. Built from multiple interacting cell populations, these engineered machines have applications in disease modeling and drug development, and as sensors that detect and respond to biological signals. We recently tested the plasticity of cells by evolving in silico designs with specific movement and behavior capabilities and used this information to sculpt self-organized growth of aggregated Xenopus skin and muscle cells. In a novel environmentin vitro, as opposed to inside a frog embryoswarms of genetically normal cells were able to reimagine their multicellular form. With minimal sculpting post self-assembly, these cells form Xenobots with structures, movements, and other behaviors quite different from what might be expected if one simply sequenced their genome and identified them as wildtype X. laevis.

These living creations are a powerful platform to assess and model the computations that these cell swarms use to determine what to build. Such insights will help us to understand evolvability of body forms, robustness, and the true relationship between genomes and anatomy, greatly potentiating the impact of genome editing tools and making genomics more predictive for large-scale phenotypes. Moreover, testing regimes of biochemical, biomechanical, and bioelectrical stimuli in these biobots will enable the discovery of optimal stimuli for use in regenerative therapies and bioengineered organ construction. Finally, learning to program highly competent individual builders (cells) toward group-level, goal-driven behaviors (complex anatomies) will significantly advance swarm robotics and help avoid catastrophes of unintended consequences during the inevitable deployment of large numbers of artificial agents with complex behaviors.

Understanding how cells and tissues make real-time anatomical decisions is central to achieving regenerative outcomes too complex for us to manage directly.

The emerging field ofsynthetic morphology emphasizes a conceptual point that has been embraced by computer scientists but thus far resisted by biologists: the hardware-software distinction. In the 1940s, to change a computers behavior, the operator had to literally move wires aroundin other words, she had to directly alter the hardware. The information technology revolution resulted from the realization that certain kinds of hardware are reprogrammable: drastic changes in function could be made at the software level, by changing inputs, not the hardware itself.

In molecular biomedicine, we are still focused largely on manipulating the cellular hardwarethe proteins that each cell can exploit. But evolution has ensured that cellular collectives use this versatile machinery to process information flexibly and implement a wide range of large-scale body shape outcomes. This is biologys software: the memory, plasticity, and reprogrammability of morphogenetic control networks.

The coming decades will be an extremely exciting time for multidisciplinary efforts in developmental physiology, robotics, and basal cognition to understand how individual cells merge together into a collective with global goals not belonging to any individual cell. This will drive the creation of new artificial intelligence platforms based not on copying brain architectures, but on the multiscale problem-solving capacities of cells and tissues. Conversely, the insights of cognitive neurobiology and computer science will give us a completely new window on the information processing and decision-making dynamics in cellular collectives that can very effectively be targeted for transformative regenerative therapies of complex organs.

Michael Levinis the director of the Allen Discovery Center at Tufts University and Associate Faculty at Harvard Universitys Wyss Institute. Email him atmichael.levin@tufts.edu. M.L. thanks Allen Center Deputy DirectorJoshua Finkelsteinfor suggestions on the drafts of this story.

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How Groups of Cells Cooperate to Build Organs and Organisms - The Scientist

September1,2020|Bio-IT World Conference & Expo Virtual kicks off in a month. The program this year includesthree days full of content, networking, and interaction across 16 tracks, plenary session, workshops, posters, awards,and happy hours.Thevirtual meeting platformoffers integrated tools to stay connected with colleagues,reach out to speakers, ask questions during presentations and live Q&A panels,and tour virtualexhibitbooths.

Andfor the first time ever, many presentations will be availableon demandafter their first showing. Attendees will be able to learn more, ask more questions, and derive more value from the program for weeks and months to come.

We are already busy marking our agendasnotations well be able to transfer to the virtual platform soon. Heres some of what is our on currentlist.The Editors

As usual, the event kicks off withworkshopsdesigned to be instructional, interactive and in-depth. This year topics include data management for biologics, a crash course in AI, data science-informed decisions, data at scale, and more.

The 2020 Bio-IT Worldplenaryprogramis exceptional.SusanGregurick, NIHs Office of Data Science Strategy, and Rebecca Baker, Director, HEAL, will share NIHs strategic vision for data science, and how thethepandemic will shape NIHs future.Tuesday, October 6

Robert Green,Brigham & Womens HospitalandHarvard Medical School will sharefascinating news on his latest sequencing project.AndNatalijaJovanovic, Sanofi Pasteur, will share pharmas view of the AI-enabled future.Thursday, October 8

A panel of experts includingSeth Cooper, Northeastern University; LeeLancashire, Cohen Veterans Bioscience;PietroMichelucci, Human Computation Institute; andJrmeWaldisphl, McGill Universitywill tackle how AI,citizenscience, andhumancomputationare working together with the help of gaming.Wednesday, October 7

And Trends from the TrenchesBio-IT Worldsannual deep dive into IT for life scienceswillcelebrate its 10th year with an all-star panelincluding VivienBonazzi, Deloitte; TimCutts,WellcomeTrust Sanger Institute;KjierstenFagnan, Lawrence Berkeley National Laboratory; MatthewTrunnell, Data Commoner-at-Large; andof courseChrisDagdigian.Thursday, October8

As commercial, governmental, and research organizations continue to move from manual pipelines to automated processing of their vast and growing datasets, they are struggling to find meaning in their repositoriessaysTerrell Russell, Chief Technologist, TheiRODSConsortium at Renaissance Computing Institute (RENCI). With an open, policy-based platform,Russell argues thatmetadata can be elevated beyond assisting in just search and discoverability. Metadata can associate datasets, help build cohorts for analysis, coordinate data movement and scheduling, and drive the very policy that provides the data governance. Data management should be data centric, and metadata driven.Wednesday, October 7

Michael C. Conway, Technical Architect, Office of Data Science, NIH NIEHSoutlinesNIEHSwork to build its own Data Commons to manage todays research data. Managing daily work while observing future trends, incorporating key capabilities, often in a tentative and piecemeal fashion, without losing sight of the big picturethis is the challenge we all face.Wednesday, October 7

Ian D. Harrow,Pistoia Alliancewill report on building a new toolkit to help life science industry implement the FAIR (Findable, Accessible, Interoperable, Reusable) principles for data management and stewardship. It provides practical support by bringing together relevant methods for tools, training and managing change, which are illustrated by use cases mostly from life science industry. These elements are assembled together as one user-friendly and freely accessible website.Wednesday, October 7

In a collection of talks and a panel discussion, a team of Gen3 users and architects present their experiences buildingpatientplatforms with Gen3. Speakers includeRobert Grossman, University of Chicago;Christopher G. Meyer, University of Chicago;Gabriella Miller,Kids First Data Resource Center;Allison Heath, Childrens Hospital of Philadelphia;William VanEtten,BioTeam; andDaniel Huston, Bristol-Myers Squibb Co.For an inside look at the collaboration withBioTeamand Bristol-Myers Squibb to set up a Gen3 data commons seeBuilding A Commons: How Bristol-Myers Squibb AndBioTeamUsed Gen3 To Build A New Data Paradigm.Wednesday, October 7

Luis A. Mendez, Bristol Myers Squibb, willpresent advances in multiparameter flow cytometry analysis using machine learning algorithms. Both t-distributed Stochastic Neighbor Embedding (t-SNE) andFlowSOMalgorithms are very effective in the comprehensive analysis and visualization of multiparameter flow cytometry data, resulting in a deeper understanding of disease biology at the single-cell level.Mendez will describe BMSscloud-based, high-performance compute environmentcoupled with GPU processing, deployed to overcome challenges with executing these CPU/RAM/GPU-intensive algorithms on large datasets.Wednesday, October 7

Rare disease patients suffer too often from long diagnostic delays and misidentified diseases. This creates a significant burden, not just for patients, but for healthcare systems.TomDefay,Alexion,will shareexamplesofcollaborationwith researchers and hospital systems to developnovel approaches for rare disease patient identification using tools like genomics, machine learning, and NLP.Thursday, October 8

Biomedical research over the last decade has become increasingly complex, and different disciplinary expertsare needed tosolve challenging scientific questions. No longer is a single disciplinary perspective enough for truly breakthrough research advances.L. Michelle Bennett, NIH NCI, explores how to build the most impactful interdisciplinary teams and how to keep them working effectively. (For more, see our conversation with Michelle atTraining Scientists For Our Interdisciplinary Future.)Wednesday, October 7

John Quackenbush, Harvard Medical School, will outline how his group uses networks tounderstandgenetic andgenomicdrivers ofdisease.By using innovative computational methods built around network representations of biological interactions, we can gain insight into the disease process, develop predictive biomarkers, and identify possible avenues of therapeutic intervention, he argues.Wednesday, October 7

ImanTavassoly, Icahn School of Medicine at Mount Sinai, will present themTOR system, adatabasehedesigned for exploring biomarkers and systems-level data related tothemTOR pathway in cancer. This database consists of different layers of molecular markers and quantitative parameters assigned to them through a current mathematical modelandis an example of merging systems-level data with mathematical models for precision oncology.Wednesday, October 7

Alexander Sherman, Massachusetts General Hospital, will describe how MGH is pursuingpatient centricity to bring such information together and bridge clinical trials data with RWD, such as data from EHRs, DNA sequences, image banks, biobanks, -omics, etc. We are introducing patient-centric approaches with a unique secure patient identification and aligning incentives for all players in a research continuum, including academia, industry, government, patient advocates, and patients.Wednesday, October 7

Exploratory visualizations generated from clinical trials and real-world data sources provide important insights into safety, efficacy, and biomarker responses to novel and standard-of-care treatments, saysPhilip Ross, Bristol-Myers Squibb.Hell explain how automation of data updates in near-real time increases the impact of this information on decision-makingand can driveclinical andbiomarkerexploration.Wednesday, October 7

Two presentersYan Ge, Director, Data Analytics, Data Science InstituteandErik Koenig, Principle Scientist, Translational Oncology, Head Strategy Innovation Management,both ofTakeda Pharmaceuticalswillpresent how aknowledge-baseanalyticsplatformhasempowereddata-drivendecisionmaking andistransformingtranslationalresearch. TheTakeda R&D Data Hub has been established to maximize the value of data, make them FAIR, increase access for efficient analysis and to drive data-driven decision making. The StrategicTranslational Oncology Research Knowledge-base (STORK) platform is a mission-critical strategic application leveraging both the R&D Data Hub and leading-edge Big Data technologies to harmonize the increasing data density of Immuno-Oncology Research and Development. STORK provides better catalogued and enriched biomarker assays data, allows researchers to intuitively and easily query internal preclinical data, clinical trials data, and external data like full-text literature and clinicaltrials.gov sources using NLP. Furthermore, STORKs self-service visualizations enable more efficient benchmarking, cross comparisons, forward and reverse translational insights to support key decision-making throughout the therapeutic lifecycle.Thursday, October 8

MatthewTrunnell, Data Commoner-at-Large(former Vice President and Chief Data Officer, Fred Hutchinson Cancer Research Center) will present theCascadia Data Discovery Initiative, and its goal to acceleratehealthinnovation andcancerresearch throughcollaboration,datasharing, anddata-drivenresearch.Wednesday, October 7

The future of the intersection of healthcare and the life sciences will be data- and process-focused, not application- or software-focused. Bringing the analytics todata is the challenge from an infrastructure and methods perspective. According to the FDA, Real-World Evidence (RWE) is defined as the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of Real-World Data (RWD): e.g., effectiveness or safety outcomes from an RWD source in randomized clinical trials or in observational studies.Sanjay Joshi, Dell EMC, leadsatopical, honest, and real-world paneltodiscuss the sources of RWD (EHR, Claims & Billing, Registries, Patient Reported Data, etc.) and their process implications for RWE and the future of clinical trials themselves.Wednesday, October 7

Many critical facts required by healthcare AI applications are locked in unstructured free-text data. Recent advances in deep learning have raised the bar on achievable accuracy for tasks, like named entity recognition, entity resolution, de-identification and others, using novel healthcare-specific networks and models.VishakhaSharma, Roche Molecular Systems,will discuss how Roche applies the greatest advances in AI for healthcare to extract clinical facts from pathology reports and radiology.Shewill then detail the design of the deep learning pipelines used to simplify training, optimization, and inference of such domain-specific models at scale.Wednesday, October 7

Researchers use biomarker and outcomes data to model and predict adverse events. However, access restrictions to safeguard patient privacy necessarily slow down the rate of discovery and increase research costs via IRB review.KimberlyRobasky, Renaissance Computing Institute (RENCI),makes an argument forsynthetic data that preserve patient-variable relationships. She willdiscuss current advances made by generative models in this area and the breakthrough AI technologies accelerating those advances.Wednesday, October 7

Digital transformation is still a driving principle in pharma R&D with the ultimate goal being to streamline processes and enable precision medicine.Anastasia Christianson, JanssenPharmaceuticals,willpresentexamples of digital technologies driving transformation and tangible results in R&D.Wednesday, October 7

While the value of FAIR data has been establishedas well as the costs of un-FAIR dataadoption lacks easy routes.Tom Plasterer, AstraZeneca, presents the Pistoia Alliance FAIR data toolkit and Innovative Medicines Initiative (IMI)FAIRplusCookbookwhichoffer frameworks to start. Key decisions on what to name things (e.g., identifiers) and their semantics (e.g., vocabularies) are critical at journey inception. Once established, FAIR knowledge graphs and FAIR analytic services become enterprise data-centric enablers.Wednesday, October 7

In less than a decade, CRISPR has evolved from a bacterial immune system to the foundation of a powerful, flexible genome editing technology that has already transformed biomedical research, spawned a $10-billion biotech industry, and is poised to make major strides in the clinic.Kevin Davies, the founding editor ofBio-IT World, has spent the past few years working closely with the CRISPR community as the Executive Editor ofThe CRISPR Journal. In this talk, he shares highlights of his new book,EDITING HUMANITY,to be released October 6, which explores the genesis of the CRISPR revolution, its impact on the gene therapy field, and the recent scandal involving the birth of CRISPR babies in China.Wednesday, October 7

Lara M.Mangravite, Sage Bionetworks, willdescribe a radically open approach to diversifyingthe AD drug portfolio. Using multi-omicand genetic models of disease built from human brain data, a suite of emerging therapeutic hypotheses are generated that complement the small set already in drug development. To catalyze rapid evaluation of these targets, target enabling packagescontaining computational and experimental resources including prototype drug compoundsare developed and openly distributed for use across the research community.Thursday, October 8

TanyaCashorali, TCB Analytics, leads a panel discussion on how to create an effective data and analytics strategy answering the questions:Whichdataareactionable? What is the end goal? How do you build out an organization? Are you sure you know what problem you are trying to solve? How do you set up an analytics environment?Shes joined by panelistsLauren Young, Beam Therapeutics, andHeather Shapiro, Pear Therapeutics.Wednesday, October 7

The Hutch usesEasyBuildfor building software containers and all software foritscomputer cluster.John Dey, Fred Hutchinson Cancer Research Center,will share more details about thesoftware stackand how the Hutchsharesitswork with the global community of EasyBuild users. Wednesday, October 7

CarolinaNobre, Harvard University, reports on the state of the art in visualizing multivariate networks.Multivariate networks are made up of nodes and their relationships (links), but also data about those nodes and links as attributes. Most real-world networks are associated with several attributes, and many analysis tasks depend on analyzing both, relationships and attributes. Visualization of multivariate networks, however, is challenging, especially when both the topology of the network and the attributes need to be considered concurrently.Nobrewillanalyze current practices and classify techniques along four axes: layouts, view operations, layout operations, and data operations.She willalso provide an analysis of tasks specific to multivariate networks and give recommendations for which technique to use in which scenario. Finally,she willsurvey application areas and evaluation methodologies.Wednesday,October 7

RituKamal, Illumina, will present IlluminasTruSightSoftware Suite, offeringready-made infrastructure to analyze and interpret rare disease variants.Powered by DRAGEN variant-calling, this software platform can evaluate all rare disease variant types within a single interface. Intuitive variant filtering, visualization and curation enable laboratories to perform streamlined interpretation and generate customizable reports.Wednesday, October 7

Biomedical researchers have access to many data sources but finding data with specific characteristics remains a challenge. Datasets have different metadata, format, and structure.TheBroad Instituteenvision a simpler and more comprehensive search capability to allow researchers to find and reuse data across many datasets.KathyReinoldproposesa cross-domain data model built specifically to facilitate search and reuseand will share methods, lessons learned, and status.Wednesday, October 7

KjierstenFagnan, Lawrence Berkeley National Laboratory, will present the National Microbiome Data Collaborative: A FAIRdataresource formicrobiomeresearch. Thismulti-lab collaborative partnership will pilot an integrated, community-centric framework within 27 months to fully leverage existing microbiome data science resources and high-performance computing systems available within the DOE complex for data access, integration, and advanced analyses,Fagnansays. She willcover some of the challenges in microbiome data sciences and howthe partnershipsaim to overcome these by creating a large, open-access repository of FAIR data.Wednesday, October 7

In a pair of talks fromBristol-Myers Squibbspeakers,Ajay ShahandAlbert Wangwill present Sage, a comprehensiveplatform forinnovation withdataand how BMS researchers use Sage to maximize real-world assets. Shah will start by giving an overview of essential components of the platform, such as uniform high-quality data ingestion, data lake enhancement with semantic integration conformance of data, and a reproducible research framework.Wang willhighlight how Sage catalogs, models, integrates, conforms, and presents patient-level metadata across all RWD assets to facilitate downstream cross-dataset analysis within an integrated managed analytics environment. This talk will touch on the business drivers for this initiative, our current progress, as well as some lessons learned.Wednesday, October 7

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A Virtual Feast: A Preview of Bio-IT World 2020 - Bio-IT World