Category Archives: Human Genetics

ROCKVILLE, Md.--(BUSINESS WIRE)-- The American Society of Human Genetics (ASHG) 2020 Virtual Meeting taking place October 27-30 will showcase global advances in human genetics and genomics research that are transforming the scientific landscape and leading to new advances in the treatment of devastating diseases.

The ASHG 2020 Virtual Meeting features more than 200 oral presentations, nearly 2,000 scientific poster presentations, 80 exhibit booths, networking and professional development opportunities, and more, making it the digital epicenter of human genetics. As always, it will be among the worlds largest events for genetic and genomic discovery, with thousands of scientists, clinicians, advocates and others participating from more than 50 countries.

As a global showcase of the latest developments in human genetics, the ASHG 2020 Virtual Meeting will provide an online venue for researchers who conduct human genetics and genomics research around the world to exchange scientific knowledge, said Anthony Wynshaw-Boris, MD, PhD, ASHG President. I am excited about the fantastic talks, posters, and special sessions, that will be presented at the Virtual Meeting.

The meeting will host chat sessions throughout the program to continue scientific conversations and exchanges around the latest scientific updates and breakthroughs. The Society also will recognize the outstanding scientific achievements of its members in the human genetics and genomics community with special awards and lectures throughout the meeting.

Not only will the ASHG 2020 Virtual Meeting host exceptional plenaries, but also concurrent programming sessions covering critical areas of the field. In addition to the late-breaking COVID-19 session, other sessions will focus on data usage and data resource topics related to human genetics and genomics. Finally, of note, the Virtual Meeting will feature human genetics and genomics research which works with participants of diverse populations, as well as perspectives from researchers working in their own communities. See all speakers and sessions and the full schedule.

We are adapting to changes in the field, the global pandemic, and the need for physical distancing by hosting our first Virtual Meeting, connecting us all through outstanding science, shared resources and information, and meaningful relationships, said Teri Manolio, MD, PhD, ASHGs Program Committee Chair. ASHGs Virtual Meeting is yet another important way we are working to connect with members and the field, as we utilize our expertise in online events to deliver the best scientific programming.

Learn more about the high-caliber speakers and explore the workshops and special sessions that are incorporated into the virtual meeting this year. Registration is open. Complimentary registration is available for media; apply for credentials. To connect for interviews, contact Kara Flynn at press@ashg.org.

The American Society of Human Genetics (ASHG), founded in 1948, is the primary professional membership organization for human genetics specialists worldwide. The Societys nearly 8,000 members include researchers, academicians, clinicians, laboratory practice professionals, genetic counselors, nurses, and others who have a special interest in the field of human genetics.

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ASHG 2020 Virtual Meeting to Showcase Innovative Research in Human Genetics - BioSpace

Germline genetic testing is essential in order to identify optimal treatments for patients with cancer, as well as detecting inherited mutations via cascade testing that could affect family members, according to John M.Carethers, MD, MACP, who emphasized that improvements to genetic testing technology and testing costs has increased not only the accuracy of, but access to these assays.

The technology in sequencing has moved from the old gels to capillary to ChIP [chromatin immunoprecipitation]-based, and has revolutionized the way we approached it. The depth of [genetic testing] coverage [has evolved], said Carethers. Sequencing technologies totally revolutionized this [process].

He added, There are some unusual situations in which additional technologies have to be used to figure out some of the ones that typical ChIP technologies don't fully explain. That has markedly changed the way we approach [testing] these days.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer (IPC) webinar on Precision Medicine, Carethers, a professor of Internal Medicine and Human Genetics at the University of Michigan, discussed recent developments in multi-gene panel testing.

OncLive: How are predictive and somatic genetic tests being utilized in clinical practice?

Carethers: In terms of germline testing, the benefit is knowing which disease you carry, and that information can also spread to other family members to understand whether they [are at an increased risk of getting a cancer diagnosis]. Sometimes, at least in my experience, [germline testing] does alleviate some anxiety. Some people get more anxious once they know they have a germline mutation, but in general, it does at least explain the reason why they're seeing certain diseases in the family. Thats the general benefit for germline testing.

The benefit of somatic testing is knowing the type of mutations that occur in the tumor; there may be a therapeutic drug or compound that is in current use that could benefit the patient. For instance, I had a patient with unresectable esophageal cancer. She was dying and her esophagus was almost completely obstructed with the tumor. She had a feeding tube put into her stomach and lost a lot of weight; she was literally counting out the days until she died. With some thought, we decided to take a sample of the tumor and do somatic testing.

She had some mutations that werent typically found in esophageal cancer, and we did have drugs [to treat her]. She was actually put on those drugs and the tumor shrunk dramatically to the point that she could eat again, she gained weight, and she lived another 5 years. Normally, she wouldn't have lasted more than a few months. The benefits of somatic testing is understanding the genetic makeup of the tumor in which you might be able to use some compounds that exist to benefit the patient. Thats the real goal of somatic testing.

There is an unusual situation for somatic testing, as well. For instance, in colon cancer, we know about Lynch syndrome, but there is also a Lynch-like syndrome. In Lynch-like syndrome, there is no germline [mutation], but the tumor has 2 somatic mutations of a mismatch repair deficient tumor. They can look like a Lynch syndrome tumor, and maybe even behave a little bit like a Lynch syndrome tumor, but they're really not caused by a germline mutation. Sometimes, somatic genetics can help us understand tumor genesis as well as ways to treat the tumor.

What changes have we seen recently in multigene panel testing? How are test results interpreted and how do they help guide treatment strategies?

There are patients who will walk in with the classic phenotype and then there are patients walking in who don't have the classic phenotype, yet they carry that mutation in the same gene. Multigene testing allows us to account for phenotypic variation.

Someone may walk in with colon cancer, the next person in the family might walk in with endometrial cancer, and the next person in the family may walk in with a skin tumor, but they all line up with the same mutation in Lynch syndrome. However, if you saw the skin tumor first, would you have thought of Lynch [syndrome]? [What about] if you saw the endometrium or the colon cancer? It depends on the specialty and the type of disease presentation they show up with. In many cases, though, the disease could be subtle.

For instance, there was a family I followed, which comprised the grandmother, mother, and daughter. The grandmother, who was well into her late 60s, had a Lynch syndrome mutation and got her colon removed appropriately. The mother was in her 40s with no cancers, but the daughter who was 21, developed colon cancer. It looked like it skipped a generation, yet, they all carry the same mutation. There's phenotypic variation, even with this exact same mutation in the family, because we're all genetically different to some, so there's probably modifiers and other things going on. However, if I can see that in this one family who I know [harbor that specific] mutation [then I know that] if multiple people walk into the clinic and have variations in their family histories and in their personal history of cancer, that we are seeing a wide phenotypic variation.

Now, instead of testing 1 gene at a time, we will test 30 or 50 genes at a time, and you can pick up some of these less penetrant genes that are causing the phenotypic variation. Sometimes there are major penetrant genes in these families.

What other barriers to germline testing need to be addressed?

We're always learning. Every year or so we add a few more genes to our repertoire and then, maybe they get on some of these panels. E3 ubiquitin ligase WWP1 is associated with PTEN hamartomatumorsyndrome, which is not on any panels, but the paper was published in the New England Journal of Medicine. We keep learning as we discover more and more of these genes. The more genes that we find tend to occur in less and less people, based on our current knowledge, but some of these patients present with these rare phenomena.

We're also finding out that some of these mutations arent specifically a change in the DNA sequencethere are methylation, or rearrangement, or even a deletion. You have to use other techniques in addition to sequencing to figure those families out or those families will be left in the lurch.

The downside of doing multigene panel testing is that now, if you push for more whole-exome and whole-genome sequencing, we have a lot more variants. One commercial lab got [results] back to me 2 months ago from a patient we had tested 4 years ago. They said, We finally have enough people [where we could determine that] his variant is not significant. It was good news. We are now more sure of variants because they now have more families in their database at the commercial lab. Sometimes it takes years to figure it out, unless we have functional analysis for all variants. Thats a big challenge right now.

Where do you hope to see the future of genetic testing head?

In a good way, genetic testing will probably [have a lower] cost and there [will be an] ease of doing it [with] whole-exome and whole-genome sequencing. It will even overtake panel testing over time because the machines are better and faster. The key, though, is having a database that you can go back and forth and analyze. Youre going to need the analytics and tools. What happens with the patient? Do I carry this [information] on a flash drive? Is it in a database I have to have access to?

It's not an easy answer and I'm not sure if the health system that a particular patient goes to is going to store all this information3 billion base pairs of informationand go back to it each time. Each place is going to have to have the right analytic tools to go back and [retrieve that information]. There are going to be some challenges with that, even though that's the way the technology is going.

The more challenging pieces [are related to] direct-to-consumer (DTC) testing. You don't always know what you're getting on those tests. We can test you for common diseases, such as diabetes and hypertension, but we also test you for BRCA1/2. In reality, very few of the DTC [tests] are doing sequencing or panel testing like we do clinically. Many of them are using single nucleotide polymorphisms (SNPs) that give you a suggestion. Many of these start from ancestry companies,and they recently moved into [testing for] these diseases because people are interested. I don't blame them for doing this, but the information they give might only [include] a fraction of the actual disease variants. If someone finds an SNP in BRCA1/2 or Lynch syndrome, you might need to see a doctor. [Based on your family history or phenotype,] we may have to send a ChIP test to verify [the results].

In some cases, people will test just to be curious, and they think they're going to have something, but there is zero evidenceno personal history and no family history. There are going to be some challenges with the DTC [testing] because we don't always know the type of test theyre getting and the information is not going to be as precise and could present challenges in the clinics. Some people are going to get upset because we're going to say, No, you don't need testing, or [patients will ask], Why does this test say I might have it but your test says I don't? We have to explain all this and those are going to be challenges.

What else would you like to add regarding the evolution of genetic testing?

There is phenotypic variability in the presentation of many of these syndromes. The standard now is multigenetic panel testing to try to assuage the phenotypic variation; we do pick up [genes in] people who we didn't necessarily think had that disease. I've been surprised too many times, so I'm not surprised anymore. A lot of these inherited conditions have phenotypic variability. If you have any suspicion or your primary care physician has any suspicion, feel free to send [a test] to our clinic because we can investigate that and do testing that's relatively cheap if there's a good cause to investigate that. It may save their life and the lives of their loved ones.

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Focusing on the Future of Genetic Testing in Oncology - OncLive

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Does cancer run in families? A genetic counselor from Baylor College of Medicine will answer that question and more about cancer genetics during the Evenings with Genetics virtual seminar on Tuesday, Oct. 13, at 7 p.m.

During the hourlong webinar, Tanya Eble, genetic counselor and assistant professor of molecular and human genetics at Baylor, will discuss cancer red flags to look for in your personal or family history, what to expect at a cancer genetics evaluation as well as gene tests for hereditary breast and colon cancer syndromes. Judy Karonika of Judy's Mission, a nonprofit aimed at increasing awareness, education and prevention of ovarian cancer, and patient advocate Nancy Khan will also speak.

Evenings with Genetics is a regular speaker series hosted by Baylor College of Medicine and Texas Childrens Hospital that offers the most current information on care and research advances for many genetic conditions. The seminars provide an opportunity for patients in the genetics community to interact with other families experiencing similar situations.

The program is free and open to the public, but registration is required. A Zoom link will be sent to all registered participants the day before the seminar. For more information, call 713-798-8407 or visit the event registration page.

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Evenings with Genetics discusses connection between cancer and genetics - Baylor College of Medicine News

"SKYMINT BRANDS and DNA Genetics share a similar brand ethos in that we are both on a mission to provide cannabis enthusiasts with the highest quality flower possible," says SKYMINT BRANDSCEO Jeff Radway. "All flower is not created equal, and DNA Genetics knows this better than anyone else, which is why our SKYMINT X DNA GENETICS collaboration truly sets a high bar in Michigan."

Launching tomorrow, October 9, at all seven recreational SKYMINT locations throughout the state of Michigan, as well as select retail partners, SKYMINT X DNA GENETICS features a premium collection of seven of the most globally awarded and sought-after flower strains, including Bakers Delight and Ztrawberriez, as well as:

Clementine Flower $701st Place, High Times Cannabis Cup 20191st Place, 710 Degree Cup

Kosher Kush Flower $701st Place, High Times Cannabis Cup 2010Top 10 Strain of the Year, High Times Cannabis Cup 20111st Place Milano Secret Cup 2018People's Choice, Cannabis Cup Brazil 2016

LA Confidential Flower $701st Place, High Times Cannabis Cup 2008

Chocolope Flower $70TEN 1st Place Awards, including 1st Place, High Times Cannabis Cup 2010

Strawberry Banana Flower $701st Judges Choice, Cannabis Cup Brazil 20161st Place, High Times Socal Cup 2016

Certified as to provenance by DNA GENETICS, each seed was hand-chosen by founders Don Morris and Aaron Yarkoni and farmed to perfection by SKYMINT cultivators. Two additional strains, Gelato Sorbet and Lemon Skunk, are still to be released by year's end, as are .7 gram pre-rolls.

"Each time we explore a potential collaboration, we look for the best possible partner in each market and SKYMINT BRANDS is that partner for Michigan," says Don Morris, Co-Founder of DNA Genetics. "The extreme level of care, commitment, and innovation that SKYMINT BRANDS infuses into its cultivation and product brands inspires great confidence."

The SKYMINT X DNA GENETICS collaboration marks a new moment in Michigan's progressive cannabis market. Recreational cannabis only came online last December, and Michigan's industry has scaled rapidly, with SKYMINT a leader in that growth, establishing 10 dispensaries in seven months with two more planned to open this year.

Since its inception in 2018, SKYMINT BRANDS has dedicated itself to creating and curating premium-crafted cannabis brands, hand-grown with expert care to power a portfolio of the finest cannabis brands available for daily wellness, healing, and recreational enjoyment. Joining SKYMINT X DNA GENETICS under the SKYMINT BRANDS umbrella are SKYMINT, North Cannabis, Jolly Edibles, and the Two Joints brand, which benefits the Last Prisoner Project.

"There's good cannabis, there's better cannabis, and then there's SKYMINT X DNA GENETICS," says Laurie Gregory, Chief Brand and Product Officer at SKYMINT BRANDS. "While all of our SKYMINT BRANDS are premium, the SKYMINT X DNA GENETICS collection delivers superior genetics, flavor, and effects for a consistent, elevated experience that's unparalleled. SKYMINT X DNA GENETICS is literally the best cannabis that our state has to offer, marking a high point for our brand and for Michigan."

Adds Radway, "SKYMINT X DNA GENETICS embodies the three pillars that inspire our work at SKYMINT BRANDS: to elevate cannabis in Michigan and beyond; to cultivate stellar, premium brands; and to leverage our resources and position within the industry to change the world and our communities for the better."

The SKYMINT X DNA GENETICS launch coincides with the company's recent transition from its founding name - Green Peak Innovations - to SKYMINT BRANDS.

"SKYMINT BRANDS reflects our belief in the exponential potential of cannabis to revolutionize lives and inspire people everywhere to feel better, live better, do better, and create better. This collaboration is a perfect example of that aim. With access to the world's best cannabis, the SKY's the limit," says Gregory.

PRESS KIT

About SKYMINT BRANDSBeginning operations in Fall 2018, Skymint (formerly known as Green Peak Innovations) is Michigan's leading vertically integrated cannabis company and the state's largest medical and recreational license holder. With two state-of-the-art indoor grow facilities, the company cultivates, processes, markets, distributes and sells a full range of branded cannabis products, including SKYMINT, North Cannabis, Jolly Edibles, the Two Joints brand, which benefits the Last Prisoner Project, and SKYMINT X DNA GENETICS. Just as SKYMINT treats its plants like people - tending to and caring for them by hand, and even playing them music - each and every product is handcrafted to ensure the safest, cleanest, highest quality products at the best value. SKYMINT products can be found at the company's SKYMINT provisioning centers and via retailers around Michigan through a robust wholesale network. As purveyors of premium-crafted cannabis, SKYMINT has developed a portfolio of the finest cannabis brands available for daily wellness, healing, or just getting high on life. SKYMINT inspires people everywhere to feel better, live better and do better. Learn more: http://www.skymint.com/dna-x-skymint/

Press Contact: Holly Aubry / HUMAN NATURE / [emailprotected] / 646.943.0541

About OG DNA Genetics Inc.DNA was rooted in Los Angeles and founded in Amsterdam in 2004 by Don Morris and Aaron Yarkoni. Over the last decade, the Company has built and curated a seasoned genetic library and developed proven standard operating procedures for genetic selection, breeding, and cultivation. In a world that is increasingly opening up to commercial cannabis activity, DNA is positioned to become the first, truly geographically-diversified company with multiple partnerships with top-licensed producers and brands that have built their companies and global presence utilizing the "Powered by DNA" model.

For more information, please visit http://www.dnagenetics.com

Press Contact: Rezwan Khan, President of DNA Genetics at [emailprotected]

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SKYMINT BRANDS -- Formerly Green Peak Innovations -- Joins Forces With DNA Genetics To Bring The World's Most Globally Awarded Flower Strains To...

Liping Liu and colleagues discuss the challenges of global collaboration for brain health research and promising future opportunities for improvement of brain health worldwide

Brain science is still in a discovery phase because of our limited knowledge of basic nervous system structure and function. We need a broader perspective of delivering meaningful outcomes to patients with neurological disorders and greater understanding of the mechanisms that underlie development of neural circuitry, how neurons encode and retrieve information, and how information interacts from one neuron to another. Knowledge of how brain activity gives rise to complex behaviours and how it adapts to external and internal changes is limited. Superficial understanding of the various senses, emotions, and cognitive functionsthinking, choice, and even consciousnesspromise innovative solutions in areas such as health, education, and 21st century economics.1 With the increasing burden of major brain diseases across the world, we need to find the most effective means to comprehensively apply modern biotechnology and to solve problems in clinical medicine.

Neuroscience is entering a new era of collaboration, in which successful new technologies, generated by large scientific projects across the world, will have a dramatic impact not only on medical science but on economics and society as well. In 2013, the US government launched the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) initiative and put forward a national brain science project. This initiative complemented the Human Brain Project in the European Union and was shortly joined by the Brain/MINDS programme in Japan and several other national initiatives from Korea, China, Canada, Australia, and the International Brain Research Organization. Coordinating these successful international programmes and encouraging broad distribution of new technologies and open accessibility of the data generated will increase their value, while promoting creativity and expertise from every source. Multidisciplinary science that leverages translational research is critical to the success of these endeavours, along with the establishment of distribution systems and sharing mechanisms of technology on human data. In support of these goals the International Brain Initiative was formed to coordinate global BRAIN projects.2. This may facilitate comparability of the data and reduce economic and social disease burden. The complexity of the human brain is reflected in how its molecules, cells, circuits, and systems enable humans to perceive, recognise, and communicate with each other, as well as to understand how our brain confers our individual identity and enables us to contemplate our place in the natural world.3 The ambitious goal of understanding the brain is being approached in various projects. Paramount to this process of tackling all the objectives is the commitment to collaboration between government and non-government organisations and integration of basic and clinical translational brain research.4

Global brain initiatives to map, monitor, and modulate brain activity will lead to a host of clinical applications. Our colleagues from the stroke and neurocritical care community look forward to technologies that can improve ability to diagnose and successfully intervene to prevent and treat severe brain injury as well as enhance the brains capability for rewiring for improved function. The Neurocritical Care Society, a multidisciplinary non-profit organisation with thousands of members around the world, is poised to take advantage of the new neurotechnologies..The society undertakes research through the Neurocritical Care Research Network.5 The fresh impetus for such research initiatives is the desire of clinical scientists to enhance our understanding of complex disease states to improve patient outcomes and maintain brain health. The main goal of the society was to foster collaborative multidisciplinary clinical research and to advance critical care research methods such as using specific integrated chips for monitoring patients with traumatic brain injury. By monitoring the electrocorticography and neurochemical signals of the injured human brain tissue, it might be possible to detect spreading depolarisations, which are associated with poor outcomes in patients with traumatic brain injury. The behind the ear wireless microplatform device also enables monitoring of mobile patients with traumatic brain injury for secondary brain injury impact.6 Recent multidisciplinary collaborative clinical research indicates that a better outcome for patients in the completely locked-in state (severe disability) or with severe stroke may be feasible using brain-computer interface training to improve motor rehabilitation.7

Further challenges are raised by the varying directions of brain research projects around the world. They have different funding mechanisms, project management structures, and approaches to ethical issues. It is imposible to achieve an understanding of the mysteries of the brain in one project aloneintegrated collective intellectual and technological support are needed from different resources. Enhanced standardisation of those elements that enable scientists to compare data and contribute to building a common knowledge base of the brain is urgently needed.

What should be standardised to construct a framework that will bring together the results of large scale brain research initiatives from different countries? Examples might include agreement on common core acquisition methods and sharing plans for human brain imaging and data, or common standards for meta data and analysis tools for single cell typing studies. Also included could be approaches to disseminate new neurotechnologies and training programmes to optimise their application to brain projects. Human genetics has already benefited from global team science. An excellent model is ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis), a worldwide network of researchers who pool brain imaging and genetic data from over 200 institutions aiming to investigate various aspects of the brain.8

Alzheimers disease is one disease where such networks could advance understanding. Amyloid deposition, intracellular tau aggregates, vascular compromise, and immune/inflammatory alteration are strongly implicated in the pathogenesis of neurodegeneration in Alzheimers disease. Sleep disturbance, changes in the brains glymphatic flow, and even effects of microbiota on brain functioning provide other contributory factors. Yet despite this new knowledge, effective therapies have been elusive. Tools from the global brain initiatives that enable investigators to interrogate the complex circuits affected in Alzheimers disease should enable the science to move from associative molecular-structural relationships to treatments that intervene to preserve circuit function.

Common worldwide data may provide insight into additional therapeutic targets, which mainly focus on transforming basic research achievements into clinical prevention and treatment. Further research into degenerative medicine, vascular biology, public health sciences, and clinical trial implementation and organisation is also important.9

As with earlier projects in genomics, astronomy, and physics, the enthusiasm of brain initiatives around the world call for strengthening international collaboration. The aim is to reduce the current and future brain related disease burden through multidisciplinary research and capacity building, promoting the development of effective prevention and intervention for neurological disorders. Box 1 summarises the challenges and opportunities regarding brain research, especially for global collaboration.

Limited resources and knowledge about the mechanisms of brain function and dysfunction

Few integrated projects provide insights into the priority and benefit of human brain research worldwide

International collaborative projects required to treat devasating neurological and mental health disorders that are major social and economic burdens on society

Organising the multidisciplinary high level basic or clinical research worldwide to take advantage of core research direction from every resource

Distributing novel technologies and sharing the generated data worldwide

The International Brain Research Organization and the International Brain Inititiave could provide support for relevant issues across the world, such as policy and ethics

What models for international collaboration might neuroscientists emulate to achieve productive research worldwide? Consultation on all potential elements would requires involvement of a wide range of stakeholders from academia, industry, and government.

To tackle this challenging task, we suggest identifying the core areas of research priorities, expanding scientific opportunities, and disseminating discoveries for the benefit of humanity. The most notable example of such collaboration in our area of medicine is the BRAIN initiative, a partnership between the National Institutes of Health, the National Science Foundation, the Defence Advanced Research Projects Agency, private foundations, and researchers.10 We have a limited understanding of brain function and the workings of neural networks. The development and application of innovative technologies that explore brain circuits over the spatial scales that range from moleculular interactions at the synapse to electron microscopic level connections, and then to mesoscale imaging of structural and functional neuroimaging will result in a dynamic picture of brain function.

As an example, gait deficits contribute significantly to functional disability after stroke. Recent technological advances in stroke gait rehabilitation have made it possible for robotic devices to provide safe, intensive training through accurate repetitive motion.11 There is evidence that electrical stimulation of the brain, as a means to further engage post-stroke neuroplasticity and enhance functional recovery, may promote recovery and improvement in symptoms. Various neuromodulation techniques are under investigation for stroke patients, including transcranial direct current stimulation, repetitive transcranial magnetic stimulation, motor cortex stimulation, and deep brain stimulation. Existing results show improvement in patients paresis in certain circumstances,12 and improved outcomes (such as the International Tourette Syndrome Deep Brain Stimulation Public Database and Registry).13

The most difficult disorders to understand are those without a known pathological signature. Recent evidence suggests that pure circuit diseases such as mood disorders may be better characterised by a combination of dimensions (emotions, cognitions, social) and a novel diagnostic system that cuts across traditional diagnostic classifications. By implementing psychological tasks and various neurovisualisation techniques, the experimental medicine approach has been used to determine specific predictors of neurocognitive and emotional abnormalities and to assess the effects of new treatments in these processes.14 New tools that could identify circuit disturbances that underly these abnormalities could serve as targets to enhance therapeutic development.

Worldwide data and methods portals with common data standards for sharing and data pooling could drive international collaboration. Such projects face huge challenges because of the unique complexity of data from an organ with billions of neurons and trillions of synaptic connections. It is therefore essential that we begin with ambitious but manageable goalsfor example, integrating mouse serial electron microscopy connectomic data with light microscopy mesoscale connectomics, single cell census studies to provide scientists with reagents for genomic access to particular cell types so they can precisely monitor or modulate brain circuits. Computer technology for informatics platforms are critical to support modelling and theory development. The Human Brain Projects platforms give scientists a single point of access to neuroscientific method, multiomic clinical data, and analysis tools from around the world.15 Thanks to the international collaborative projects, the field of functional neuroimaging has advanced substantially, showing the value of big data science.16 On the clinical side we have seen the value of harmonisation of variables among relevant studies to promote greater comparability across collaborating research projects.17

Machine learning and artificial intelligence techniques based on big data are increasingly being used in both understanding and diagnosis of neurological disorders and offer a new model for personalised management. Machine learning techniques could be used to delineate the categories and predict the patients outcomes with various conditions. For example, artificial intelligence has been successfully used on pattern recognition of electroencephalogram or neuroimaging abnormalities for diagnostic purposes in patients with epilepsy.18

However, these efforts are only the beginning. A synergistic international effort could provide greater global impact and better use of precious research funding, including government, industry, non-governmental organisations, and individual contributions. It requires rewarding the groups or team for the collective effort rather than a few lead investigators. In the international brain project, expertise is unlikely to lie in a single country. The removal of national barriers for funding team science seems a desirable goal but is difficult politically and even more difficult when it entails intellectual property claims. The Human Brain Project exemplified team science funding within the European Union; the US BRAIN initiative makes funding available to any researcher from any country, as long as the proposed project is deemed worthy by the study sections that review it.

Importantly, new tools to map, monitor, and modulate brain circuits in humans hold great promise not only for the treatment of neurological disorders but also the ethical challenge to understand how these tools should be used. The answers may depend on cultural beliefs, but the processes for establishing ethical guidelines should be global and transparent. Many countries have incorporated ethical issues into the design of their brain programmes.19

In conclusion, the collective success of bridging these projects into a global collaboration that aims to understand the scientific basis of brain structure and function could have a key role in this era of academic development. In addition, it would be of benefit for science as a whole, open up a new strategic direction and promotion for brain disease prevention, create new industries, and ultimately achieve a better life for individuals and the population.

Limited research resources and knowledge of nervous system structure and function make it difficult to achieve a better outcome for those with neurological disorders

A new collaborative era of neuroscience encourges broad distribution of novel technologies and opens accessibility of the data generated worldwide

Further priorities and strategies to promote global collaboration on key brain health and initiatives are warranted to increase the opportunities

Contributors and sources All the authors proposed the idea of this manuscript. LL drafted the first version and all the authors critically reviewed and revised the manuscript. LL is director of the neurocritical care unit at Beijing Tiantan Hospital and her focus is on stroke care and clinical research. VFs research is focused on global epidemiology and prevention of neurological disorders, with a particular focus on stroke. RLS is executive director of the McKnight Brain Institute and director of the Miami Clinical and Translational Science Institute and immediate past-president of the American Academy of Neurology. WJK is co-director of the NIH BRAIN Initiative and previously worked in stroke and neurointensive care services.

Competing interests: We have read and understood the BMJ policy on declarations of interest and declare that the study was supported by grants from the Ministry of Science and Technology of China (2016YFC1307301) and National Natural Science Foundation of China (81820108012).

Provenance and peer review: Commissioned; externally peer reviewed.

This article is part of a series launched at the Chinese Stroke Association annual conference on 10 October 2020, Beijing, China. Open access fees were funded by the National Science and Technology Major Project. The BMJ peer reviewed, edited, and made the decision to publish these articles.

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Promoting global collaboration for brain health research - The BMJ

DCeased: Dead Planet reveals that one unique aspect of Jon Kent, Superman's son, makes him the DC equivalent to Dragon Ball Z's Gohan, Goku's son.

WARNING: The following contains spoilers for DCeased: Dead Planet #4 by Tom Taylor, Trevor Hairsine, Gigi Baldassini, Rain Beredo, and Saida Temonfonte

Two of the most powerful figures in modern fiction -- Superman of the DC Universe and Gohan of theDragon Ball franchise -- both have sons in their core continuities. Both of these sons have proven to be honorable in their own way, but they have a second similarity that could see them fully overtake their father's absurd power levels.

In DCeased: Dead Planet #4, Jon Kent of theDCeased universe just proved to be getting stronger than his father because of his half-human genetics -- giving him the same natural advantage Gohan had inDragon Ball Z.

RELATED:DCeased Shows How Strong Jon Kent's Superman REALLY Is

Jon Kent is the son of Superman and Lois Lane. This means Jon actually has the genetics of both a human and a Kryptonian. This allows him to absorb solar energy like his father, increasing his power over time as he grows older. If he were to follow in his father's specific footsteps, he could eventually develop enough strength to rival his father. There was some question of whether or not his half-human status would complicate that at all, or if he would be weaker as a result.

But it turns out, at least in theDCeased reality, that isn't the case. Damian Wayne, the current Batman,hypothesizes that Jonwouldn't be weaker than his father. Instead, his half-human/half-Kryptonian status means he's actually becoming more powerful than his father -- which tracks with aspects from the core DC Universe hinting that Jon could even prove to be stronger than Superman's upper limits when he reaches his prime, as he shows when he knocks out Orion with one punch.

This is surprisingly similar to a concept also introduced inDragon Ball Z. While theDragon Ball franchise as a whole focuses largely on Goku,Dragon Ball Z specifically charts Gohan's growth from Goku's young son to his capable and powerful successor. As the series progresses, Gohan's half-Saiyan status comes up multiple times.

RELATED:DCeased: Hope At World's End Gives A Classic Speedster His Sad, Fitting End

Like his father, Gohan's Saiyan biology grants him certain perks, such as a tail at birth and the ability to come back from life-threatening injuries even stronger than before. But on top of this, Gohan's half-human/half-Saiyan status means he actually has more potential than Goku ever did. He has his true potential unlocked multiple times, and his ultimate transformation at the conclusion of the Cell Saga into the Super Saiyan 2 form proved he could take his father's place as Earth's defender.

This means that Gohan and Jon Kent have the same advantage in combat, allowing them to deal with almost any threat, even more than their fathers. While both Goku and Superman have new forms that could see their power levels increased exponentially beyond their sons (such as Goku reaching the Super Saiyan Blue form or Superman absorbing enough solar energy to enter his Golden Superman form), their natural forms might not ever reach the full limits of their sons. While Gohan might have not have reached the same levels of power as Goku's most recent forms, Gohan has proven powerful enough to counter Kelfa, a Saiyan fusion from Universe 6 that was strong enough to fight back against Goku even when he was in his Super Saiyan Blue form.

It's a promising future for Jon, and gives him a unique similarity with his anime counterpart. Even if this DC Universe is a deeply broken place filled with death and despair, Jon's considerable power levels are something of a silver lining.

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Patients with cystic fibrosis experience recurrent lung infections that eventually destroy their airways, shortening their average life expectancy to 50 years in Canada. Current drug treatments, which target a malfunctioning pathway in cells that causes the infections, are costly and have varying effectiveness.

Now, with funding from Medicine by Design, a researcher at the Hospital for Sick Children (SickKids) is combining stem cells, gene editing and computational modelling to try to hijack an alternative cell pathway in the hopes of restoring lung function in these patients.

If successful, our study will be the first to provide proof-of-concept that this alternative approach to treating cystic fibrosis is effective, saysAmy Wong, a scientist working in developmental and stem cell biology at SickKids who is also an assistant professor in the department of laboratory medicine and pathobiology in the University of Torontos Temerty Faculty of Medicine.

Wongs project is one of seven across U of T and its affiliated hospitals that have been awarded 2020New Ideas AwardsandSeed Fundawards from Medicine by Design. Through a $1 million investment, Medicine by Design is supporting research aimed at advancing new concepts expected to be important to regenerative medicine in the coming years. The funded projects will have potential impacts in diseases and conditions such as vision loss, amyotrophic lateral sclerosis (ALS), intestinal disease in premature babies and more.

Supporting novel strategies and approaches is crucial to moving regenerative medicine into the future, saysMichael Sefton, executive director of Medicine by Designand a University Professor at U of Ts Institute of Biomedical Engineeringand thedepartment of chemical engineering & applied chemistry in the Faculty of Applied Science & Engineering.

Our 2020 New Ideas project portfolio integrates mathematical modelling, physics and computational biology with stem cell biology and biomedical engineering, and strengthens engagement with clinicians who are key to translating our research into patient impact. We are particularly delighted this year to support so many outstanding early-career researchers, who will ensure Toronto remains a global leader in regenerative medicine for years to come.

Wong is one of three investigators to receive a 2020 New Ideas Award, which is valued at $100,000 per year for up to two years. Four additional projects were selected for Seed Fund Awards of $100,000 each for one year to further develop their potential.

Medicine by Design selected the funded projects from among 36 short-listed proposals, which were evaluated and ranked through an external peer review process. Applications were submitted by clinicians and researchers at U of T and its affiliated hospitals from a wide range of disciplines including biochemistry, biomedical engineering, developmental and stem cell biology, immunology, neuroscience and surgery.

Medicine by Design builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers James Till and Ernest McCulloch. Regenerative medicine uses stem cells to replace diseased tissues and organs, creating therapies in which cells are the biological product. It can also mean triggering stem cells that are already present in the human body to repair damaged tissues or to modulate immune responses. Increasingly, regenerative medicine researchers are using a stem cell lens to identify critical interactions or defects that prepare the ground for disease, paving the way for new approaches to preventing disease before it starts. Medicine by Design is made possible thanks in part to a $114-million grant from theCanada First Research Excellence Fund.

Current cystic fibrosis drug treatments target a genetic mutation that causes epithelial cells, which line the airway and act as a barrier against viruses, to function improperly. The mutation affects the function of an important ion channel in cells, called CFTR, which helps to maintain the right balance of fluid in the airways. Poor function causes mucosal obstructions in the airways and prevents clearance of foreign pathogens, which leads to chronic infections and ultimately destroys airway tissue.

In her project, Wong will explore an alternative ion channel in the epithelial cells to determine if it can be hijacked and used to compensate for the lack of function caused by the mutant CFTR. The research will be conducted using a combination of stem cell-derived lung models, gene editing and computational modelling.

Wongs project builds on decades of cystic fibrosis research at SickKids, where the cystic fibrosis gene was first identified 30 years ago.

To date, more than 2,000 mutations in the cystic fibrosis gene have been identified, says Wong. SickKids scientists and U of T researchers have become the epicentre of incredible cystic fibrosis research to understand how this disease works at the genetic and molecular level.

Wong says that, while the idea of targeting an alternative pathway is not necessarily ground-breaking on its own, its the array of tools now available that makes the idea a potential game changer.

We have access to an incredible resource of primary cells and stem cells from more than 100 individuals with cystic fibrosis harbouring various mutations. Wong says.Our lab has developed human lung models from stem cells that can be used to model lung disease such as cystic fibrosis. And with new advanced tools in single-cell genomics and gene-editing, coupled with key collaborations for computational modelling, we are poised to find new therapeutic targets for cystic fibrosis.

Leo Chou, an assistant professor at the Institute of Biomedical Engineering, andHyun Kate Lee, an assistant professor in the department of biochemistry in the Temerty Faculty of Medicineboth Medicine by Design New Investigators are also leading 2020 New Ideas projects.

Chou, along with co-investigatorsJulie Lefebvre, a scientist at SickKids and U of T assistant professor of molecular genetics, andValerie Wallace, a senior scientist at the Krembil Research Institute, University Health Network and a U of T professor of laboratory medicine and pathobiology and ophthalmology, will focus on cell transplantation in the retina, a process that has demonstrated encouraging pre-clinical results such as partial vision restoration in several animal disease models.

Recent research had demonstrated that this restoration is a result of the transfer of proteins complex molecules required for the structure, function and regulation of the bodys tissues between host tissue and donor cells. But the scope of that transfer process is not well understood. Chous project will develop an imaging approach to detect the transfer of mRNA molecules between host and donor cells. The outcomes from this project will inform the future design of cell transplantation therapies and lead to novel methods to deliver therapeutics. This project could improve therapies for retinal diseases and visual impairments, and inform strategies for other degenerative disorders.

Lee and co-investigatorPenney Gilbert,an associate professor at the Institute of Biomedical Engineering, will look at a common but not well-understood structure called the neuromuscular junction (NMJ), which mediates communication between neurons and muscles throughout the body. Defects in NMJ integrity and function underlie fatal diseases such as ALS. NMJ diseases, which affect more than 500,000 people globally, lack effective treatments. This project will use stem cells derived from reprogrammed skin cells of healthy people to develop NMJs in culture. Through high-resolution imaging, the healthy human NMJs will be studied both on their own and along with NMJs built from ALS patient cells. Through this work, the research team aims to identify genes to target to improve the health of NMJs, which could eventually help prevent or delay NMJ degeneration and even promote regeneration.

Michael Garton, an assistant professor at the Institute of Biomedical Engineering, has received a Seed Fund award to tackle the challenge of translating the genetic tools of synthetic biology an area of research that aims to create or redesign biological components using engineering methods into effective medical therapies against a number of diseases.

But they are difficult to translate into human therapies, Garton says, because the bodys T-cells immune cells that detect and destroy cells containing foreign material will identify these tools as foreign and destroy them.

Instead of switching off the T-cells, Gartons goal is to use computational modelling and high-throughput screening to selectively turn off the bodys foreign antigen display system so the immune system will still respond to foreign invaders when necessary, but allow cells containing synthetic tools to survive. If successful, this approach could enable a new generation of synthetic biology-enhanced cell therapies for a range of diseases.

Medicine by Design funding will help to facilitate the integration of synthetic biology and regenerative medicine and aid the development of cell-based therapies that perform better than nature, says Garton.

Other Seed Fund projects will encompass research in repairing the heart after paediatric cardiac surgery, treating an intestinal emergency in premature babies and creating a database for cell lineage paths.

John Parkinson, a senior scientist at SickKids and a U of T professor of biochemistry and molecular genetics, along with co-investigatorsJason Maynes, Wasser Chair in Anesthesia and Pain Medicine at SickKids and a U of Tassociate professor of anesthesiology and biochemistry, andWilliam Navarre, an associate professor in the department of molecular genetics, will investigate manipulating the microbiome, or community of microorganisms in the gut, to improve cardiac repair in post-operative treatment of a congenital heart disorder. Through a process that will identify prebiotics in breast milk that help enhance the production of molecules that research has shown can aid cardiac repair, the team will organize both observational (how disease alters the microbiome) and interventional (how the microbiome alters the disease) multi-site trials, which will provide the opportunity to immediately translate findings into changes in patient care regimens and improve outcomes.

CliniciansAgostino Pierro, a surgeon at the Division of General and Thoracic Surgery at SickKids and a U of T professor of surgery and physiology, and Philip Sherman, a senior scientist and gastroenterologist at the Division of Gastroenterology, Hepatology and Nutrition at SickKids and U of T professor of dentistry, pediatrics and laboratory medicine and pathobiology, have proposed a novel way of enhancing gut repair for a common intestinal emergency in premature babies, called necrotizing enterocolitis (NEC). A leading cause of death for these infants, NEC causes complications such as blindness, intellectual disability, repeat hospitalizations and gut damage even in those that survive. This project will look at whether intestinal organoids organ-like structures grown in the laboratory from stem cells that mimic some of the functions of native intestines can potentially stimulate repair of the gut and recovery from NEC. The project will define how to best transplant organoids, identify how the organoids protect the intestine from injury and assess if organoid transplantation is a valid new treatment for NEC.

Lincoln Stein, who is head of adaptive oncology at the Ontario Institute for Cancer Research and a professor in the department of molecular genetics at U of T, has received seed funding to build a database called Cytomics Reactome, which will be freely available to Canadian and international researchers. The database will build on recent technologies that open the door to the possibility of deciphering cell lineage paths the series of steps that lead a young, undifferentiated cell into a specialized one at single-cell resolution. To accelerate the path from basic research to clinical application, the database will systematically organize pre-existing knowledge of cell lineage paths into a comprehensive, interactive and easily accessible map that can serve as a framework for interpretation and integration of the latest experimental findings.

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Findings have shown that patients with cancer are at an increased risk of developing severe illness due to coronavirus disease 2019 (COVID-19). The COVID-19 positive cancer population is also more likely to be African American, present at an older age, and have an increased risk of intensive care stay and intubation, as well as a longer duration of hospital and intensive care time, compared with the COVID-19positive population without cancer.1

As more data become available, patterns of health inequities during the COVID-19 pandemic emerge. During presentations delivered as part of the COVID-19 and Cancer meeting, hosted by the American Association for Cancer Research, investigators highlighted biologic and socioeconomic factors that play a role in the growing disparities in care and severity of risk of complications for patients with cancer and COVID-19.

The United States has the highest number of reported COVID-19 cases in the world, with deaths occurring more often in patients with advanced age and comorbidities. The disparity for COVID-19 deaths is seen for all age groups, with African Americans showing the highest death rates at any age. Compared with non-Hispanic Whites, both African American and Hispanic COVID-19 deaths outpace those of non- Hispanic Whites, even at younger ages.

In my own state of Michigan, African Americans share of cases, as well as deaths, greatly outstrip the proportion of African Americans in the state population, John M. Carethers, MD, professor and chair of the Department of Internal Medicine and professor of human genetics at the University of Michigan Medical School in Ann Arbor, said during his presentation.2 Overall, African Americans make up 13% of the population but make up 23% of COVID-19 deaths. If you assess this per 100,000 population, [deaths in] non-Hispanic Whites occur at a rate of 27 per 100,000, [whereas] African Americans are at a whopping 62 per 100,000.

In a cross-sectional study evaluating the association between COVID-19 infection and mortality rate from 369 counties of 7 states, African Americans were observed to be more vulnerable to the virus than any other ethnic group. Variables irrespective of race that were most closely associated with death rates in the study were medical disabilities, lack of grocery mobility, and poverty.3

In a cohort of patients hospitalized with laboratory-confirmed COVID-19, cancer status, race and ethnicity, and descriptive statistics for baseline characteristics were collected to analyze the cumulative effects in patient mortality. Findings showed a trend toward higher rates of death in African Americans, men, and patients on Medicare/ Medicaid in the COVID-19positive cancer population, but those associations were not found to be statistically significant.1

There was a disproportionate number of men and specifically, African American men, who were coming in and requiring hospitalization, Steven S. Chang, MD, director of the Head and Neck Cancer Program at the Henry Ford Cancer Institute in Detroit, Michigan, said while presenting the data. Once they are in the hospital, their outcomes were similar regardless of race, but the factors that led to the emergency room door were probably the drivers of morbidity.

Can Baseline Biological Factors Explain COVID-19 Outcomes?

It has been surmised that higher mortality and infection rates among racial minorities may be due to disproportionally increased nonCOVID-19 comorbidities seen in stratified patient subgroups.

African Americans in particular carry more health conditions making them more susceptible to COVID-19, with a higher vulnerability index in the middle and older ages and higher numbers of comorbid risk factorscompared with non-Hispanic Whites, Carethers said.

However, recent studies suggest that this may not represent the full scope of the issue. In one study, the risk of testing positive for the virus by race and ethnicity compared with the non-Hispanic White population carried higher odds ratios (ORs) in patients who identified as Hispanic/Latino (age-adjusted OR, 2.69; 95% CI, 2.14-3.39), African American (age-adjusted OR, 3.69; 95% CI, 2.83-4.81), and Asian (age-adjusted OR, 1.87; 95% CI, 1.36-2.58). When adjusted for sex, history of diabetes, heart disease, lung disease, kidney disease, current smoker status, and body mass index, corresponding ORs in the same patient subgroups did not change drastically: multivariate OR, Hispanic/ Latino (2.68; 95% CI, 2.13-3.38); African American (3.51; 95% CI, 2.68-4.60); and Asian (1.97; 95% CI, 1.43-2.73).4

Hydroxychloroquine, a drug used to prevent and treat COVID-19 in the early days of the pandemic, was since found to offer no benefit to infected patients.5 In patients who have a sodium channel variant known as p.Ser1103Tyr-SCN5A, seen among 1 in 13 African Americans, there is a higher risk of heart arrhythmia and sudden cardiac death, which can be exacerbated by COVID-19 related conditions such as hypoxia, myocardial injury, cytokine storm, and use of QTc-prolonging drugs.6

The coalescing of these 3 items puts the patient at extremely high risk for sudden cardiac death, said Carethers, although he noted that there arent any study findings to confirm this association.

Sexual dimorphic responses to COVID-19 may be due to expression of the receptor ACE2 and serine protease TMPRSS2 for S protein priming, which both are necessary cellular factors for virus entry to human cells.7 Preexisting conditions may explain why these have upregulated expression in certain patients. In patients with asthma, those who were men, African American, and/ or had diabetes all had increased ACE2 and/ or TMPRSS2 from collected sputum cells, providing rationale for monitoring these subgroups for COVID-19 outcomes.8 Patients with lung diseases, including cancer, also have increased expression of TMPRSS2.9

Impact of Socioeconomic Factors

Carethers also pointed out that a societal picture could provide the greatest rationale for disparities in infection rates and outcomes in patients with COVID-19.

It starts with socioeconomic inequality, where you have lower status, lower level of education, and difficult access to health care that causes downstream consequences, Carethers said.2,10 This in turn causes changes to physiology, which include alterations to the lung and gut microbiome, increased localized inflammation, and compromised immunity. That affects the pathophysiologic health morbidities of cancer, obesity, diabetes, COPD [chronic obstructive pulmonary disorder] and asthma, hypertension, and cardiovascular and chronic kidney disease.

The high unemployment rate, in large part caused by the pandemic, worsens inequities in health care. According to the Bureau of Labor and Statistics, the rate of unemployment in May was at 13.3%, the highest since level since the Great Depression. Importantly, job loss for many patients also leads to loss of medical insurance and in turn reduces access to cancer screening.

In a study that used data from the National Health Interview Survey, the relationship between unemployment, health insurance status, and cancer screening was examined to inform the potential lasting effects of COVID-19. Forty percent of patients who were unemployed were also uninsured versus roughly 10% of those who were currently working, with unemployed individuals more likely to have Medicaid. Racial minority groups were also more likely to be unemployed than employed, including Hispanic and African American respondents.11

Controlling for nonmodifiable risk factors, unemployed individuals were less likely to be up to date on breast and colorectal cancer screenings, leading the investigators to conclude that unemployment is adversely associated with guideline-recommended care.

This is concerning because we know that cancer screening can potentially save lives, Stacey A. Fedewa, PhD, an epidemiologist and senior principal scientist in the Surveillance and Health Services Research Program at the American Cancer Society, said while presenting the study data. Because a growing number of people are losing their jobs and several racial and ethnic minority groups are more likely to be unemployed, this could drive disparities even further than what is seen now.

Carethers concluded by reflecting on how socioeconomic and biological factors together explain why these differences in outcome may exist. In many ways, the disparities observed with COVID19 may start from socioeconomic vulnerabilities that enter a vicious cycle of comorbidities, increased ACE2 and TMPRESS2 expression that [boosts] ones susceptibility to COVID-19, and lead to severe illness and death, he said. If one survives, they become more vulnerable from the aftereffects ofCOVID-19 and more socioeconomically disadvantaged with loss of jobs.

Although Carethers acknowledged that there is no quick fix for these issues, he is optimistic that bringing these data to the surface will help undermine some of the structural issues that are responsible for aggravating health disparities. COVID-19 has enhanced the visibility of some of the [structural inequalities] that we have in the United States, and most people are seeing that, he said.

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COVID-19 Shines Light on Disparities in Care for Patients With Cancer - OncLive

Understanding of fibromuscular dysplasia (FMD), a rare blood vessel disease, is making the jump from the laboratory to the clinic with new findings about a genetic variant.

Researchers found the mutation in a gene that is associated with classical Ehlers-Danlos Syndrome as well, in multifocal FMD. That means it could help clinicians understand whether a person inherited the disease from a relative or another mechanism, in affected families.

We identified four independent families with the same genetic variant in COL5A1 and vascular disease in a pattern of dysplasia-associated arterial disease, including arterial dissections and multifocal FMD, says senior author Santhi Ganesh, M.D., an associate professor of internal medicine and human genetics, and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center. Notably, the variant appears to have been inherited from a shared ancestral founder.

Ganesh says the implication of this finding is that other carriers of this variant may exist in the population. The pattern of arterial involvement among carriers of the COL5A1 G514S variant is unique, providing clinicians with clues for when to suspect its involvement.

The identified genetic variant meets clinical criteria for pathogenicity a first for FMD, she says.

Further, additional variants in the COL5A1 gene were associated with a higher rate of arterial dissections among individuals with multifocal FMD.

Paper cited: A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia. Arteriosclerosis, Thrombosis, and Vascular Biology. DOI: 10.1161/ATVBAHA.119.313885

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Early stage investment strategies and dealmaking in the age of COVID-19 became topics during the Biopharm America meeting, itself held virtually this year because of the pandemic. Kevin Johnson, partner and co-founder of European life sciences backer Medicxi, hailed an unprecedented upswing on the financial front. There is no winter, he said. Its amazing.

Johnson spoke with Steve Dickman, founder and CEO of the consulting firm CBT Advisors in Cambridge, Mass., on the same day that Johnsons firm closed its 200 million (US$234 million) secondary fund, led by Pantheon with co-lead LGT Capital Partners.

Drug discovery per se is not the hard bit, Johnson said; what matters most is understanding the biology of a potential therapy by way of human models. There is definitely a big role for what I will call computing enterprises to help, particularly with clinical trials and clinical trial management, patient records thats hugely laborious and important to get right, he said. But simply finding a drug, by whatever means, that seems to work in preclinical models doesnt turn him on. My old tech colleagues keep sending me stuff related to mostly unvalidated work. Im starting to sound like a stuck record, but I dont care, is the short answer, he said.

The death knell for anything is, We wont know if this works until we put it into the clinic, Johnson said. Im sorry, but no. We consider that to be a 20 million bet, and its probably more in the U.S. Even once a set of convincing human genetics data turn up, the matter becomes one of faith. Early stage drug discovery projects are a lot like religion, he said. Its a question of how much you believe, without necessarily having evidence to support that belief. As you go along, more people come into the church with you, until you get to the point where you dont need the church.

Dickman recalled the early days of what would become the breast cancer drug Herceptin (trastuzumab, Roche Holding AG), which had a solitary champion in then-CEO of Genentech, Kirk Raab. Consensus in the company was that the HER2-targeting prospect ultimately would not work and should be discontinued. The more people you ask, the more likely you are to get a huge range of opinion about anything, Johnson acknowledged. The trick with that is to ask as few people as possible. Dickman wanted Johnsons best guess about drug candidates or platforms likely to be hot in the coming months. I honestly dont know, he said. If whatever youre doing is in the interest of the patients, at some point thats going to win through, regardless. Thats the only reason any of us is here. Have that as your lodestone, and hope that the rest of the world catches up in sufficient time that you can make a return for your fund.

Medicxis portfolio includes companies such as Z Factor Ltd., of Cambridge, U.K., which was spun out of the University of Cambridge. In August, the firm dosed the first human volunteer with ZF-874, its treatment for alpha-1-antitrypsin deficiency. The drug is meant to act as a molecular patch for the faulty protein, allowing it to fold correctly, relieving the liver burden of polymer accumulation while providing fully functional Z-A1AT in the circulation to protect the lungs.

Despite COVID-19s forced shift to virtual rather than face-to-face encounters, activity by his firm has been pretty intense this year by comparison to previous years, Johnson said. Obviously were doing everything by Zoom, and its been surprisingly effective. Weve managed to do some fairly elaborate things, made new investments, [and did] follow-ons as well as hiring.

With regard to negotiating via screen rather than handshake, you can get 90% there with people you havent met before, Johnson said, though theres always a little bit of a niggle at the back of your mind that you havent finally completed the picture. Hes on the watch for behaviors that might signal problems later. Im not sure youre going to see them even if youre face to face, he said. You generally only see those in the trenches, when things get tough. If youve been around for a while you know very well that some people seem like normal individuals right up to the point where theres money on the table, and then they display psychotic tendencies. I dont think you should overstate how much you can read people in an interview or pitching type of situation. Everybodys selling. Its not real. His firm often starts with a small seed financing to test drive the other party, he said, pointing out that the situation is not a one-way street. It may well be that theres some allergy to us, as well as the other way around.

Dickman, who previously served as a principal at Techno Venture Management, recalled a certain energy in the room when evaluating opportunities. I always felt that trigger [to do the deal] when it was there, he said. In the same way that audio technology cuts off the lowest lows and the highest highs, maybe the highs are lost in electronic interaction, he speculated.

Johnson doesnt think so. Im spending more time with people in this medium than I would in an office situation, he said, and is able to take the measure of entrepreneurs, who tend to be hard-to-manage mavericks. Peoples energy does come across you can still read facial expressions and body language. Some non-verbal cues are missed, but thats a necessary hazard now. You put the closed sign on the door and walk away, otherwise, he said.

Biopharm America ends Thursday.

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Biopharm America: Of 'psychotic' behavior and term sheets in online dealmaking's brave new world - BioWorld Online