Daily Archives: March 21, 2022

Mount Desert Island Biological Laboratory, a non-profit research institute in Maine, is funding a new initiative to increase the use of nonmammalian models in early drug development. The initiative, dubbed MDI Bioscience, aims to turn to species like zebrafish (Danio rerio), C.elegans, axolotls (Ambystoma mexicanum), and African turquoise killifish (Nothobranchius furzeri) to evaluate potential therapeutic compounds at scale before theyre tested in mammals or enter human clinical trials, potentially hastening and honing the decision-making process in early drug discovery and reducing the reliance on mammals such as mice. MDI Bioscience hopes to evaluate drugs before money is spent on costly mammal research, to speed the drug development process, and reduce the number of mammals, and animals in general, used in scientific research. Jim Strickland, the director of MDI Bioscience, says that these goals are aligned the general research practice to reduce, replace, and refine (three Rs) animals in research. The three Rs seek to address the potential ethical issues involved in animal research, which become heightened in higher order animals like rodents and primates.

The Scientistspoke to Strickland about the program and its goals.

Jim Strickland

Anna Farrell, MDI BIOLOGICAL LABORATORIES

Jim Strickland: We wanted to enable more efficient discovery of new drugs and new pharmaceutical compounds by using nonmammalian species such as zebrafish, C. elegans, axolotls, in order to help pharmaceutical companies better characterize early-stage molecules, and be able to quickly select those molecules with the greatest promise before more significant investment is made in mammal studies and other regulatory based activities that we know take quite a bit of time and expense to complete in preparation for human clinical studies.

JS: Were building this organization from the ground up with an eye toward the future. Well have a state-of-the-art facility to work from and to run these studies from, with the goal that eventually, as these models become regulatory models, well be able to quickly transition to a full GLP [good laboratory practices] lab . . . [which are] the requirements that govern whether or not data can be accepted by the FDA for regulatory decisions.

Certainly, to start out and as we grow, we want to leverage the incredible expertise that already exists in the lab . . . . The faculty in the lab . . . will stay true to their basic science objectives, but when their expertise is additive to answering key questions for drug discovery, theyll be consulted and lab staff will also participate in work initially as we grow.

JS: Our primary model at this point is using zebrafish, which are well known as being excellent models for replicating both human physiology, human genetics, and human disease. Zebrafish share over eighty percent homology with human disease-causing genes. They provide excellent comparability to humans in terms of their genetic composition. And that makes them very attractive models for early-stage drug discovery. But additionally, C. elegans . . . also provide a novel model for high throughput assays for evaluating toxicity in early-stage drug development. In the future, were working with two novel nonmammalian models, the axolotl, which has incredible potential to help teach us a lot about how tissue is regenerated. And then also, in a similar light, the African turquoise killifish also has some really unique properties that are specific to tissue regeneration that make it really interesting in terms of evaluating these mechanisms and potential ways of rescuing function.

JS: There are a number of benefits to the nonmammalian models. For one, they can be easily imagedzebrafish embryos are transparent. They work well with microscopy, and that lends the model to high-throughput screening because you can generate a large number of embryos and test multiple different compounds at the same time or at different concentrations. That gives you a really robust early assessment of a compound library to see if youre seeing a desired effect or undesirable toxicity. Then, compared to mammalian species, theyre very cheap to work with. The cost of mammalian research keeps going up and the use of zebrafish and other models is cost and time-efficient compared to mammalian species. . . Lastly, theres tremendous similarity between humans and zebrafish on a structural and a cellular level. If you were to take a slice of a kidney from a human and take a slice of a human or a kidney from zebrafish, if you looked at them under a microscope, theyre almost indistinguishable.

JS: Yes. Zebrafish in particular are becoming more widely used in early phase drug discovery. Were not the only lab that's focused on zebrafish for early-stage work. Theres really a growing consensus that these models can help reduce the use of mammals in the future.

But from a regulatory perspective, were not there yet. The ability to substitute nonmammalian models for mammal models and support . . . an application for human clinical studies . . . isnt currently something that is achievable. However, I think theres a growing amount of data . . . that shows that translation from zebrafish to mammals and ultimately to humans.

JS: Most [studies on drugs that make it to human clinical trials], and those in mice, or rats or dogs follow very specific guidelines set up by the ICH [International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use]. Theres a very prescribed pathway for using mice, rats, and dogs. Thats a different focus than what were working on with zebrafish and C. elegans. What were looking to do is to create genetic models where we can use CRISPR-Cas9 gene editing to essentially replicate the genetic condition that a drug might be trying to target. The important thing is that at this point in development, which is well before you would be contemplating the toxicology studies for initiation of human clinical studies, were able to create those disease models, and also then allow for new drugs to essentially confirm whether or not, based on the disease pathophysiology, theyre actually able to restore function . . . well before they get to regulatory studies.

Most drug discovery work is focused on single-cell systems. Cell analysis is still the predominant mechanism for determining whether or not theres an efficacy signal for a compound. Bringing whole systems biology into drug development brings the ability to ask if there are any downstream toxicology effects beyond the single cell that would involve any other organ systems, or see if there are undesirable secondary effects on a nontarget organ that need to be considered and may ultimately present a problem in later development. From that perspective, it gives you the ability to accelerate the use of whole systems biology earlier in drug development . . . as opposed to waiting to later phases to introduce mammal species.

JS: Our hope is that we can help pharmaceutical companies become more efficient in finding those diamonds in the roughthe molecules that have great potential to influence human disease and sufferingand that using these technologies will drive some of the costs out of development by helping identify those compounds that should move forward, those compounds that should move forward earlier in development, before significant costs are incurred. Ultimately, if we can make drug discovery more efficient, then that translates into reducing costs of drugs, and drug development overall. But the significant costs associated with drug development, which have been estimated at 2.5 billion [US dollars], are tough to reckon with as long as only one in five thousand drugs make it to market.

JS: I think its too early to know whether these models are ultimately going to be more predictive than the mammalian models. But certainly, theres always going to be a need to evaluate novel compounds in other species before they move into and to humans.

JS: These are great models to investigate efficacy at the molecular level, but theyre also great models for investigating rescue of a phenotype. Phenotype drug discovery is certainly a very hot topic because its been shown by some studies to have a higher success rate, and actually finding drugs that are successful and make it to market. Many of these models have excellent phenotypes of disease that enable phenotype-based drug discovery approach. There are strong phenotypes that can be used along with these models that make them attractive.

JS: For example, we can use indicator species [and] fluorescent biosensors. If theres an upregulation of a particular biomarker, the fish or the embryo will actually light up in the presence of those biomarkers. Simple things, like retinal circulation in the eye, arrhythmias of the heart, or glomerular function in the kidney. Even velocity of movement can be good phenotypes for specific diseases.

JS: In the short term, the goal is to provide a really reliable service to pharmaceutical companies that helps to answer either key questions around mechanisms of disease that then provide good feedback on what a desired target would be, or actually replicating models and disease so that if theres a particular target that theyre going after, we have the right tool to help them evaluate compounds and their efficacy and toxicity early on. The longer-term goal is to then take it to the next level and work with regulators in the US and Europe to have these models accepted and to be able to use them. I dont think theyll ever supplant the use of mammals, but they will certainly be good alternative models in cases where they have a really predictive effect.

Editors note: This interview has been edited for brevity.

Correction (Match 15): The original caption for the photo of Jim Strickland was incorrect.The Scientist regrets the error.

More here:
Oust the Mouse: A Plan to Reduce Mammal Use in Drug Development - The Scientist

Ministerial foreword

The UK is a global leader in genetics and genomics. This has never been more evident than in the last 2 years, where collectively we have led the world in virus and human genome sequencing to counter the COVID threat and added 500,000 whole genome sequences to the UK Biobank research dataset.

In 2020 we published our overarching Genome UK the future of healthcare strategy, which set out our vision and clear aspirations for how we will transform genomic healthcare over the next 10 years. In 2025 we will be marking the half-way milestone in the Genome UK 10-year timescale, and measurable progress in the next 3 years will be critical to demonstrating successful delivery. To achieve this progress, we have set out here a series of shared commitments for UK-wide implementation. We are committed to working together along with our delivery partners across the UK to implement these commitments, and, in doing so, realise the potential of genomic healthcare for the benefit of patients across the UK and around the world.

In developing these shared commitments, we have engaged in open dialogue and collaboration across the UK, recognising the differences in our respective healthcare systems and structures.

We believe that these shared commitments will help to ensure better coordination of our joint ambitions for genomics research and healthcare so that these can flourish in each of our nations and across the UK. Through better UK-wide coordination and collaboration, we will further strengthen our ability to share expertise and establish new collaborations and partnerships with others worldwide, securing our global leadership in genomics and the wider life sciences and ensuring we remain an attractive location for research and development investment. These shared commitments present a clear statement of our resolve to work together to deliver better health outcomes across the UK.

In September 2020, the UK government published Genome UK the future of healthcare, setting out the governments 10-year strategy to create the most advanced genomic healthcare system in the world, delivering better health outcomes at lower cost. The strategy also describes a vision for the UK to be the best location globally to conduct genomics research and grow new genomics healthcare companies, with a goal to increase private sector investment.

We want to ensure that patients across the UK can benefit fully from genomic healthcare, through a more preventative approach, faster diagnosis, and personalised and better treatment leading to better long-term outcomes. Researchers and industry will be supported in their research and its applications and incentivised to secure the UKs position at the forefront of genomic research in the world.

In May 2021, the UK government published its 2021 to 2022 implementation plan for Genome UK, setting out priority actions for the financial year 2021 to 2022 in England, with contributions from the Scottish and Welsh Governments outlining their approach to implementation.

Genomics is a fast-moving field and we have therefore adopted a phased approach to research and implementation which will allow us to review our commitments and take action to reflect emerging science and latest research findings. The 2021 spending review, which set departmental budgets and devolved government allocations to 2024 to 2025, provides an important and timely opportunity to collectively agree high-level commitments with which we will progress implementation of the Genome UK vision over the next 3 years. In 2025 we will be marking the half-way milestone in the Genome UK 10-year timescale, and measurable progress in the next 3 years will be critical to demonstrating successful delivery.

There are many areas where UK-wide collaboration in genomics has already been successful, the SARS-CoV-2 genome sequencing in response to the COVID-19 pandemic provided an excellent example of this. In the coming years, UK-wide coordination will continue to provide significant opportunities to enhance benefits for patients, such as joint genomic technology evaluation and better integration of genomic and health data in secure trusted research environments.

We remain committed to delivering genomic healthcare across the UK, while recognising the devolved nature of healthcare policy and the resulting different approaches to the development of genomics in healthcare. In this context, our shared commitments form part of our second phase of Genome UK implementation, setting out joint, UK-wide, high-level commitments for the period 2022 to 2025. Recognising the devolved responsibilities, the shared commitments will be followed by 4 separate implementation plans, with the UK government and the devolved governments each aiming to publish these by the end of 2022. The separate implementation plans will reference the shared commitments, incorporating and building on them, in addition to setting out more detailed commitments for each government.

In taking these commitments forward, we will be guided by the 8 shared principles stated in Genome UK and in particular the following principle, which will underpin our approach to working together:

We will work together across the UK to realise the potential of genomics for the benefit of patients and ensure that the genomics services thrive in each nation. We will engage in open dialogue and collaboration, recognising that health is devolved and there are differences in NHS structures and systems.

The shared commitments have been developed in collaboration with the genomics community and our delivery partners. High-level coordination and delivery progress will be considered by the Genome UK Implementation Coordination Group which is led by the Office for Life Sciences and has UK-wide representation. This arrangement will allow the UK government and the devolved governments to continue with, or put in place, their own reporting and governance arrangements.

The National Genomics Board is chaired by the Minister for Technology, Innovation and Life Sciencesin the Department of Health and Social Care (DHSC) and brings together senior decision makers and representatives from across the genomics sector, including senior officials from the devolved governments. The purpose of the board is to provide strategic oversight and to work collaboratively across the UK to harness the benefits of genomic healthcare ultimately helping to ensure delivery of the vision set out in Genome UK.

As part of these shared commitments, we agree that UK government and devolved government ministers will engage regularly on the outcome of National Genomics Board discussions.

Finally, the UK genomics healthcare policy landscape is vibrant and complex, with a wide range of diverse organisations either delivering or overseeing clinical services and policy programmes. To progress the commitments in this agreement, we will seek to minimise duplication of effort and resource by sharing information about existing processes, groups and structures and, with mutual agreement, utilise these when appropriate.

The following commitments are set out across the 3 pillars of Genome UK:

And the 5 cross-cutting themes covering:

Genome UK vision: tohelppeople live longer, healthier lives byusing genomic technologiesto identifythegenetic causes for disease, to detect cancers earlier and provide personalised treatments to illnesses.

Genomic technologies are already revolutionising the way in which patients are diagnosed and treated across the UK and this is set to accelerate rapidly in the years ahead.

At the same time, the devolution of healthcare and clinical service commissioning means that there are differences in how genomic healthcare has so far been implemented across the UK. However, we have a wealth of experience and leadership in diverse areas of genomics that can be shared across the UK to drive improvements in patient care. For example:

All of these are examples of healthcare systems in each UK nation beginning to transform through adoption of genomic healthcare. It is our ambition to look at current areas of difference in approach and work on how we can address these for patient benefit. For example, the Genomic Test Evaluation Working Groups established by NHS England and Improvement have been designed to bring together UK-wide expertise to collectively evaluate new genomic science and technology for genomic testing of rare and inherited diseases, cancer and for pharmacogenomics, enabling commissioning decisions to be made in our respective health services.

Pathogen genomic sequencing is another area where UK-wide collaboration is important and never more so than in our collective tackling of the COVID-19 pandemic.

At the beginning of the pandemic, in April 2020, the COG-UK (COVID-19 Genomics UK Consortium) was set up to provide a UK-wide SARS-CoV-2 genome sequencingcapacity. COG-UK supported public health agencies in the analysis of SARS-CoV-2 to identify and monitor variants of concern and to track the introduction and spread of COVID-19.

Since 2021, delivery of a national SARS-Cov-2 genomics service has been led by the 4 national public health agencies working with partners including the Wellcome Sanger Institute and CLIMB-COVID. Coordination across the UK was overseen by the UK Strategic Public Health COVID-19 Genomics Advisory Board. At its final meeting the board endorsed the transition to a wider UK Pathogen Genomics Board. Work to take this forward will commence in financial year 2022 to 2023. To date, the UK has shared over 2.25 million genomes on public databases with the international community.

The UK Rare Diseases Framework, published in January 2021, is another important initiative that fosters UK-wide collaboration and outlines a national vision for how the UK will improve the lives of those living with rare diseases. As around 80% of rare diseases have an identified genetic origin, the UKs strengths in genetics and genomics have clear potential to accelerate diagnosis and improve understanding of rare conditions, thereby driving improvements in care for patients with rare disease.

Finally, while diagnosis and personalised medicine, and research form distinct pillars of Genome UK, we are clear that they cannot be implemented in isolation. Our shared principles state that health care systems and research programmes (including those funded by the medical research charities as well as industry) will work in partnership for patient benefit, and it is this interaction and partnership that leads to the many exciting and important advances in genomic research and its applications, opening up new routes for diagnosis and novel treatment opportunities. We are therefore committed that all parts of Genome UK should interact with and cross-fertilise each other to ensure high-quality research outcomes, which are already leading to improved diagnoses for UK patients, more personalised treatment and better patient outcomes.

Our shared commitments are:

NHS Wales (via the Welsh Health Specialised Services Committee) works closely with NHS England and Improvement regarding the implementation of advanced therapy medicinal products (ATMPs) and the enabling pathways needed from the genetics service. This is achieved by NHS England and Improvement sharing their horizon scanning information with NHS Wales to inform capacity planning in Wales for ATMPs and the associated genetic services impact. NHS Wales is also well represented within the National Institute for Clinical Excellence (NICE) committee structures, including the Highly Specialised Technology Committee, which has primary responsibility for considering rare disease ATMPs, which further enhances horizon scanning and involvement in decision making. NHS Wales is also represented within the NHS England and Improvement Specialised Commissioning processes, including attendance at the Rare Diseases Advisory Group.

Genome UK vision: use genomics to:

Genomics is changing the future of health and medicine, and has the potential to transform our model of healthcare from treating illness and disease to preventing illness, or detecting it at very early stages, and supporting healthy lives. Prevention and early detection are key objectives for our healthcare system benefitting the still healthy individual through early, and often cheaper, health interventions, and also benefitting the patient at early stages of diseases offering earlier, more effective treatments. In most cases, early intervention will improve health outcomes, while also reducing treatment and care costs and helping to ensure the sustainability of the NHS into the future.

Screening is the process of identifying healthy people who may have an increased chance of developing a disease or condition, thereby allowing individuals to receive more frequent monitoring or for treatment to be initiated at an earlier stage. Genomic technologies have the potential to play an important role in screening, for example via whole genome sequencing or through the generation of polygenic risk scores, however there is work to be done to consider and address some of the ethical and privacy concerns raised by these technologies, as well as evaluating their utility in our health service. The UK National Screening Committee advises ministers and the health services across the UK about all aspects of screening and will play an essential role in appraising the viability, effectiveness and appropriateness of any new screening programmes.

We will collectively investigate the value of new genomic technologies, such as polygenic risk scores (PRS), that have the potential to identify those at highest risk of future disease and who would benefit from enhanced screening or targeted treatments and health interventions. The concept ofPRS derives from genetic analyses of participants in UK Biobank, the largest and most intensively genetically and phenotypically described longitudinal cohort anywhere in the world, linking into the rich UK health record systems. PRS combines the effects of very large numbers of genetic variants to identify people who are at particularly high risk of a condition. PRS have the potential to transform public health, but many questions remain before determining whether and how they can be used routinely at scale including the most robust disease applications for PRS and how the technology might be rolled out in the health service.

Our shared commitments are:

The UK National Screening Committee (UK NSC) advises ministers and the NHS on screening by drawing on research and consulting stakeholders. Some rare conditions need a more detailed consultation particularly when the science is complex and the evidence more limited. An example of this is tyrosinemia type 1 (TYR1), a very rare serious genetic condition. Newborn blood spot screening for TYR1 could potentially identify affected babies sooner, so they could be treated earlier.

The UK NSC commissioned Warwick University to build a model which compared what happens now with what would happen if screening was introduced. The model was based on an estimate of 7 babies being born each year with TYR1. Without screening, the model predicted that 4 of the 7 would be detected before symptoms develop. With screening, it modelled that all 7 would be picked up.

The UK NSC team used cohort data and information from other countries to provide evidence to support the screening pathway from the point of electronically identifying the babies to be tested, to the point of babies screening as positive and treatment outcomes. The team also worked with experts to understand how it is to live with tyrosinaemia and gain views of the benefits and harms of treatment options. These case histories were used to provide data for the model and to illustrate the consultation document.

The model concluded that screening for TYR1 would do more good than harm, but the costs per unit of additional benefit (quality-adjusted life years, QALYs) are high compared with NICE thresholds. The UK NSC is now consulting on whether it should recommend TYR1 screening given the estimated costs combined with uncertainty around aspects of the evidence. This process is one example of how the UK National Screening Committee uses modelling, expert views and consultation to provide a recommendation on whether an end-to-end screening programme, such as those based on genomics tests, is offered to patients. Delivery of screening programmes is the responsibility of the NHS in each nation.

Genome UK vision: continue to lead the world in genomic research.

The UK has been at the forefront of discovery-led and translational genomics research for decades and we are home to a number of internationally leading genomic research assets. UK Biobank has sequenced the exomes and whole genomes of its 500,000 participants which represents the largest collection of genome sequences anywhere in the world, all of which are linked to participants detailed NHS health records. Similarly, with the 100,000 Genomes Project, Genomics England holds the largest global collection of whole genome sequences from patients with cancer and rare diseases. Both UK Biobank and Genomics England are now also linking imaging data to already available clinical and genomic datasets.

The UK is also a world-leader in clinical and healthcare research thanks to our exceptional health and care research ecosystem including the NHS, world class universities and research infrastructure (including that funded by the National Institute for Health Research in England, Health and Care Research Wales, Health and Social Care Research and Development Division in Northern Ireland and NHS Research Scotland), a strong life sciences sector, and world class medical research charities and regulators.

Our joint vision for UK clinical research delivery highlights clinical research as the single most important way in which we can improve healthcare by identifying the best ways to prevent, diagnose and treat conditions. The UK is already one of the top 3 destinations for delivery of commercial early phase trials and delivered 12% of all global trials for innovative cell and gene therapies in 2020. Our combined strengths in genomics research, clinical genomics and clinical research, therefore, now offer unique opportunities to identify and approach patients who, as a result of genomic or genetic diagnosis, may be eligible for specific studies and who may in the future form part of a recallable clinical cohort for clinical trials, to discover new treatments in rare and common diseases.

The UKs investment and expertise in genomics mean that we now have an unparalleled opportunity to use genomic research assets to drive the next generation of life sciences discoveries. We will therefore work together to support post-pandemic recovery and growth in clinical research to deliver genomics-enabled clinical trials and support the growth and research and development of innovative genomics-focused companies.

In England, the Department of Health and Social Care will publish the final version of its data strategy Data Saves Lives in Spring 2022. The strategy sets out the critical role of health and research data in the transformation of the health and care sector. The current draft strategy includes commitments that will empower researchers across the UK with the data they need to develop life-saving treatments and new models of care, make progress towards bringing together genomics data assets and work with NHS England and Improvement to ensure genomic data generated through clinical care is fed back into patient records. This includes safe environments to securely analyse peoples sensitive health data such as the rich genetic and genomic data hosted by Genomics England, UK Biobank and Our Future Health, alongside one of the worlds most comprehensive collections of disease registries.

Another area where the UK life science sector has a unique opportunity to coordinate, collaborate and combine our expertise is functional genomics. Whole genome sequencing and other genomic tests have identified thousands of genetic variants known to be implicated in disease pathogenesis. But relatively little is known about their function and the challenge now is to understand how these variants mediate their effects, both in order to further our understanding of disease and to speed up successful drug development. Novel molecular and cell biology tools, including single cell sequencing, dynamic gene expression profiling, and systematic CRISPR, combined with insights from genomic datasets and integrated with advanced imaging and pathology, will provide opportunities for high throughput approaches to understand the role of variants and identify novel drug targets. The Medical Research Council and UK Research and Innovation partners, as major funders of discovery and translational science and research, are well placed to convene and coordinate such an initiative.

Given the rapid advances in large-scale genomic and other -omic assays, many of which utilise disruptive technologies that have been developed within the UK (such as Illumina and Oxford Nanopore), the UK is extremely well placed to take advantage of research assets that combine genomic and other -omics data at scale. With large-scale genomic and metabolomic data already available, the UK Biobank a UK-wide and internationally renowned research asset has the ambition to add proteomic data on 500,000 participants to characterise the molecular profile of its study participants in order to further power impactful life sciences research. In addition, its ambition to incorporate the use of long-read sequencing technologies will greatly improve the understanding of the impact of structural variation on human disease and wellness, and may additionally lead to the UK Biobank becoming the worlds largest epigenetic database.

Our shared commitments are:

Genome UK vision: the UK model will be seen as a leader in strong and consistent ethical and research governance of genomic data and apply regulatory standards that support rapid healthcare innovation, and maintain public and professional trust.

Genomic data is unique to every individual. Although small genetic changes will occur in different cells and tissues in our body throughout our lives, our genome will remain our constant, unique identifier. People and patients are therefore right to demand that their genomic data is handled sensitively and securely. The possibility of creating a life-long individual genomic data resource generates distinct questions regarding who should have legitimate access to this data and how, when and to what purpose it should be analysed, processed and communicated to the individual. Other important issues include ensuring that patients have sufficient understanding to support autonomous decision making in genomic healthcare, especially regarding what are likely to be more complex diagnosis and treatment decisions.

In implementing genomic healthcare, we want to harness the tremendous power of genomic and genetic information combined with other health data to be able to provide more timely, improved diagnosis and offer better, equitable and more personalised treatments and access to clinical trials. To enable these advances, it is important that the public and patients can be reassured that ethical questions regarding the handling of genomic data in research have been considered in a comprehensive way, with public and patient participation, and that these questions are addressed with robust data governance and secure data protocols.

Working together on these ethical frameworks for genomic healthcare, we will build on our strong record of examining ethical issues in bioscience and health and in developing robust models of governance and regulation. In doing so, we can lead the world in the ethics and regulation of novel applications in genomic research and healthcare, and most importantly maintain the trust of patients and the public.

Our shared commitment is:

Genome UK vision: build and maintain trust in genomic healthcare, ensuring that patients, the public and the NHS workforce are involved and engaged in its design and implementation.

We are committed to ensuring that patients and the public are at the heart of implementing the vision in Genome UK. As we have set out in our strategy, we must empower and enable patients and the public to have confidence in the potential of genomic healthcare and help shape equitable delivery. A recent report by the Government Office for Science includes evidence that suggests the public can generally see the potential benefits of genomics but are also aware of its potential negative impacts on privacy. A public dialogue by Genomics England on its whole genome sequencing research pilot came to a similar conclusion there was broad support for such an initiative provided that the right safeguards were in place.

The DHSC Data saves lives draft strategy also recognises the need to deliver truly patient-centred care, which puts people before systems, so people will have better access to their personal health and care data and can understand exactly how it is used. People will only share their information with confidence if they feel that there are proper safeguards in place, and that those entrusted with their data will keep it safe.

An important part of empowering people is to ensure greater understanding and awareness of the benefits of genomic healthcare and allowing people to make informed choices. The COVID pandemic has raised public awareness of the power and benefits of clinical research and provided an example of the relevance and importance of concepts such as genetic variation in population health. We hope that in implementing our vision for Genome UK we can build on this awareness and interest.

Our shared commitments are:

Genome UK vision: deliver UK-wide, coordinated approaches to data and standardise the way in which genomic data is recorded.

Genomic data is already transforming the way in which patients are diagnosed and treated for diseases and is enabling researchers to discover the next generation of medicines and diagnostics. The UK is home to many world-leading institutions that house genomic data. However, these have tended to be developed in isolation for a specific purpose, leading to poor interoperability and difficulty in co-analysing different datasets. To implement our vision for data set out in Genome UK, we plan to link, or federate, trusted research environments (TREs), including those hosted by UK Biobank, Genomics England and Our Future Health, creating secure spaces where accredited researchers can access and securely analyse sensitive data without breaching privacy. This means that in-depth analysis can be undertaken on rich multimodal datasets, but without identifiable information ever being seen by researchers and analysts. In March 2022, initiatives to progress this work were announced in England.

In Genome UK we set out a number of ambitions to transform our capabilities in genomic data over a 10-year period, based on a set of agreed principles and use of shared data standards that would allow a federated approach to data sharing and improved use of AI and machine learning tools across databases.

We aim to collectively build on our successful UK-wide data collaboration during the COVID-19 pandemic, such as those pioneered by the COG-UK consortium and the UK Joint Biosecurity Centre. We also aim to work closely with units developed following the pandemic such as the UKHSA Centre for Pandemic Preparedness, leveraging connections with the WHO on their Genomics Strategy, the International Pathogen Surveillance Network (IPSN) and other bi- and multi-lateral agreements on surveillance, modelling and forecasting.

Genomic data is much more useful when combined with wider healthcare information, such as scanned pathology and radiology images, blood tests or hospital admission statistics and data initiatives such as the SAIL (Secure Anonymised Information Linkage) database in Wales are already aiming to achieve this. When combined, this data allows researchers to make more informed links between genetic changes and disease development, improving the accuracy of diagnosing genetic conditions and providing a platform to launch drug discovery programmes. This kind of analysis is accelerated by the latest developments in artificial intelligence and machine learning.

Across the UK, multiple pathogen genomics services already exist, delivered at varying levels across England and the devolved administrations. Many of these services have ISO 15189:2012 medical laboratory accreditation, and all are dependent upon digital infrastructure to enable the generation of actionable information from sequence data. These services often exist in silos, creating barriers to sharing approaches and data across the UK, creating inequalities of service across the UK because of the current digital systems that exist to provide current services.

In contrast to existing pathogen genomics services, the sequencing response to the COVID-19 pandemic has seen unprecedented co-creation across the UK, and across healthcare/public health, academia and government. In response to an urgent need, a complete analysis platform for UK SARS-CoV-2 sequence data, CLIMB COVID, was built in less than 3 days in March 2020. This platform was put in place to provide a single data sharing and analysis platform which would bring together all UK SARS-CoV-2 genomes, wherever they were generated, and enable their analysis in real time. Providing real-time analysis on a single, combined UK dataset has enabled the generation of actionable intelligence at multiple scales ranging from outbreak analyses for infection prevention and control in hospitals, up to information on the shape and progression of the pandemic across the UK, to inform government policy. Collectively CLIMB COVID currently stores and analyses over 2 million SARS-CoV-2 genomes from across the UK, with the data and analysis outputs being actively used by the 4 UK public health agencies as well as numerous NHS trusts.

The exploitation of pathogen genomics data as part of the COVID-19 pandemic paints a picture of what is possible in a future where pathogen genomics data is rapidly shared across the UK as required. With shared data and common analysis approaches, expertise can also be more effectively pooled and analyses can be undertaken more collaboratively across the UK public health agencies for the benefit of patients and the public. The federated model also means that each nation is able to use the data to meet their local needs.

The success of the SARS-CoV-2 genomics efforts in the UK has been a federated approach to sequencing and analysis underpinned by a multi-node data processing infrastructure which works to standardise analysis and enables work to be undertaken on a UK-wide basis. This infrastructure, underpinned by data sharing agreements that span the UK public health agencies, provides a validation of a future federated approach, and demonstrates the enormous potential that exists through working collectively across the UK to improve how we link, combine and use our genomic data.

Our shared commitments are:

Genome UK vision: support and enable healthcare staff to deliver the benefits of genomics by training and supporting them to acquire the relevant knowledge and skills, and developing clinical pathways and standards of care.

The ambition of the Genome UK vision cannot be achieved without ensuring that the workforce have the necessary skills and knowledge to deliver genomic healthcare. Staff need to understand how genomic tests fit into clinical pathways, identify which patients require which type of test, and be able to interpret and communicate the results of these. For UK patients to receive the benefits of the latest advances in genomic technology and infrastructure, we need a workforce that develops in parallel, so that we empower healthcare professionals with the confidence and up to date knowledge needed to deliver these innovations. This will involve embedding formal education in genomics into speciality training programmes, as well as providing clinical staff with the resources to stay up to date with the latest advances in the area and utilise the available clinical pathways. By creating a National Framework for genomics education, we can ensure consistency of capability across the UK.

Key delivery partners in this work are Health Education England (HEE) and its Genomic Education Programme, which supports the NHS Genomic Medicines Service and ensures that the 1.2 million-strong NHS workforce has the knowledge, skills and experience to keep the UK at the heart of the genomics revolution in healthcare, and the Academy of Medical Royal Colleges, which sets the standards for how doctors are educated, trained and monitored through their careers.

Our shared commitments are:

Genome UK vision: make the UK the best location globally to start and scale new genomics healthcare companies and innovations, attracting direct investment in genomics by the global life sciences industry and increasing our share of clinical trials in the UK.

In July 2021, the government and the life sciences sector published its Life sciences vision. The vison sets out the governments and the sectors collective ambition for the UK to build on the scientific successes and ways of working, from COVID-19 to tackling future disease challenges (including cancer, obesity and dementia), ageing, secure jobs and investment and become the leading global hub for life sciences.

The vision recognises that to remain competitive in the life sciences and deliver on its ambition, the UK will need to focus relentlessly on areas in which it already has, or can gain, a competitive advantage such as genomics and health data. It also recognises that, for genomics, our ambition needs to be to create scale. We already have fantastic expertise, tools and world-leading initiatives in UK genomics our challenge is how to bring these together in a way that is transformative and places the UK firmly ahead of its competition, while making it a valued partner for international collaboration and an attractive location for investment.

This can be achieved through working closely with the sector on the existing and planned initiatives included in these shared commitments, such as enhancing our genomic UK-wide research infrastructure, large pilot studies to evaluate variants and their role in predicting disease risk, evaluation of new genomic tools for early disease detection, new tools for improved cancer diagnosis and delivering a world class offer to support functional genomics studies.

The UK has a diverse industrial life sciences sector, comprised of large multinationals, SMEs and spinouts all of which bring unique value and expertise to the UKs genomics ecosystem. The innovations coming from the commercial UK genomics sector and their international partners and collaborators will underpin developments in research and healthcare for years to come. It is vital that we capitalise on the UKs existing strength by continuing to foster an environment that allows companies to develop new treatments, deliver effective innovations to patients and grow at scale.

Our shared commitments are:

In our Genome UK strategy, we set out, for the first time, a comprehensive and ambitious vision for the future of genomic healthcare: a future where genome sequencing, genomic tests and integrated genomic and other health data will help to detect the risk and very early stages of disease to support early intervention, and where genomic and other -omic technologies can speed up diagnoses and support the development of better, more precise treatments for many diseases, including cancer.

Here we commit to following through on this vision by working together we will achieve better coordination and collaboration on genomic healthcare for the benefit of patients across the UK, while recognising the differences in our respective healthcare systems and structures. Our commitments will strengthen our ability to share expertise and establish new collaborations and partnerships to progress genomic healthcare not only across the UK but worldwide, securing our global leadership in genomics and the wider life sciences.

See the article here:
Genome UK: shared commitments for UK-wide implementation 2022 to 2025 - GOV.UK

Capillary Electrophoresis (CE)is a technique used in the laboratories that can separate ions based on their electrophoretic mobility with the use of an applied voltage without overheating. The advantages of the system include high accuracy, efficiency and higher reproducibility. This electrophoresis technique is widely used in biosciences and clinical research.

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Growth by Region

North America accounted for the largest market share owing to the increasing focus by stakeholders on research projects that involves proteins, associated biomolecules and also genes. The growth in Europe, is due to the growing research activities in the fields related to genomics and proteomics coupled with stringent regulatory requirements in pharmaceutical manufacturing industries. Asia-Pacific region is also one of the lucrative markets showing noticeable growth due to rising focus on structure-based drug design developments.

Drivers vs Constraints

The market is mainly driven by advantages over other molecular separation and analysis technologies due to its improved efficiency, high accuracy as well as greater reproducibility. However, the growth of the market is hindered by the high cost of the equipment as well as the availability of other electrophoresis systems in the market.

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Industry Trends and Updates

Agilent Technologies, Inc., an American public research, development and manufacturing company had completed its acquisition of Advanced Analytical Technologies, Inc., a provider of capillary electrophoresis solutions for fully automated analysis of a wide range of molecules for USD 250 million in cash.

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Thermo Fisher Scientific, an American biotechnology product development company had launched its new capillary electrophoresis (CE) system which is designed to offer a low-throughput, cartridge-based system for Sanger sequencing as well as fragment analysis at European Society of Human Genetics (ESHG) conference held in Copenhagen, Denmark.

Continue reading here:
Capillary Electrophoresis Market predicted to experience noticeable growth in the future ChattTenn Sports - ChattTenn Sports

From mesmerizing symmetry of spiraling sunflower seeds to mirror-like sides of the human body, patterns dominate nature. Aesthetic appeal aside, what advantage does repetition afford?

The question baffles experts, but a group of scientists have a controversial answer: It's the wrong question. A young professor at the University of Bergen, Dr. Iain Johnston, asked a different one: Can something inherent about evolution explain the prevalence of symmetry?

According to Johnston, the answer lies in probability. Evolution favors simple genetic codes over complex ones a principle called "simplicity bias" drawn from theoretical computer science before natural selection even comes into play. Patterns in organisms are just a symptom of that preference.

"The beautiful symmetry that we see everywhere is primed to appear," Johnston told Salon. "Simplicity bias in biology exists, and it's favored without needing to invoke any specific mechanism."

In other words, the Fibonacci spiral evidence in a nautilus shell or a head ofRomanesco broccoli is a byproduct of nature being efficient in its genetic code.

RELATED:What makes Romanesco broccoli so mathematically perfect?

Given the diversity of organisms that do so across every branch in the tree of life and every scale down to the molecular level, evolutionary biologists have generally hypothesized that symmetrical forms emerge frequently as a result of natural selection. Long-standing debate has surrounded the precise mechanism, but with the understanding that life must prefer patterns for some competitive edge.

"It's too much to be JUST natural selection," tweeted Dr. Chico Camargo. "This simplicity appears in vertebrates and invertebrates, in plants and bacteria, in RNA secondary structures and in the cell cycle, in the shape of the goddamn COVID-19 virus. There's no selective pressure that can explain all that."

The research team published a paper last Friday in Proceedings of the National Academy of Sciences that could topple that assumption. What they found was that the presentation of phenotypes, displayed traits, from genetic code, resembled the selectivity of a computer algorithm.

"We don't need to look at a flower and say, 'That was selected because it was symmetric,'" he continued. "There's some preference just from the way evolution works as an algorithm."

Using computational modeling the team demonstrated how their hypothesis, based on algorithm information theory, functions at the genetic level.

"Nature is exponentially biased towards these simple outputs, and in the RNA, you see this very nicely," asserted corresponding author, Dr. Ard Louis. "Rather than it being a bias toward symmetry, it's a bias towards these low outputs with low descriptional complexity."

With a twist on the "infinite monkey theorem" given enough time, paper, and ink a monkey could hypothetically replicate a work of Shakespeare Louis explained that genetics could be vastly more complex and disordered than they are. The odds are not likely though. He compared the greater number of genetic materials they found in the model to files one might zip on a computer.

"Symmetry emerges from what evolution is not necessarily through a specific selective pressure in a given circumstance, and at the same time it has the corollary advantage of making things more robust in biology," concluded Johnston.

From an engineering standpoint, repetition breeds stability. Compare a pile of randomly stacked rocks of various shapes and sizes to a stone building. Congruent, organized stones give the latter construction structural integrity. Patterns in nature can be similar. The approach taken in this study does not imply that natural selection has no role, but evolution can not account for all of these.

"Evolution has literally trillions of shapes to pick from, and yet, biological structures often show symmetry and simplicity," Camargo wrote.

Natural selection is process not an engineer. It is unable to anticipate what traits may or may not be advantageous, Camargo added.

"Elsewhere, there's evidence of this simplicity bias in models of neuron development, in studies of plant morphology, in teeth shapes and leaf shapes, and cell differentiation," Camargo elaborated.

Read more:
The weird reason symmetry abounds in nature may have to do with our genes striving for efficiency - Salon

G

rew up with a grumpy parent? The fear dawns that with every passing year youre unstoppably trudging towards that testy transformation your temper shortening in inverse proportion to wrinkles lengthening. With every sarcastic comment muttered to a forgetful waiter, with every idiot involuntarily barked at Question Time, the miserable metamorphosis feels pre-ordained. And science seemed to support the idea that resistance was futile against this coming curmudgeonliness. As recently as 2005, an influential paper claimed that 50 per cent of peoples happiness was determined by their genes. Becoming a grumpy git was part of your inheritance.

But if I may momentarily stop swearing at the TV, pause the dour determinism and deliver some good news: we now know that were not entirely doomed by our parents genes. Not just the doom and gloom DNA, but the genes linked to all manner of dispositions and diseases youd rather werent passed on like diabetes and heart disease. Thats because the rapid leaps and bounds in genetics in recent years have transformed how we understand the nuanced role that genes play in our health and wellbeing and its all looking a lot less pre-determined.

We once believed that having the genes for a complex disease was the key to explaining why some people are more likely to be affected by an illness such as diabetes. Not anymore, says Professor Vittorio Sebastiano, an epigeneticist at Stanford University. Whats crucial, he says, is in fact gene expression. In very basic terms, whether genes are activated or not. In other words, having a good gene but not being able to express it or activate it in the right way could lead to illnesses, relates Professor Sebastiano.

Conversely, you might have a genetic predisposition to diabetes or depression, heart disease, or hundreds of other genetically linked conditions but if the offending combination of genes is not activated, then youre unlikely to develop the condition.

The idea that genes can be switched on/off that its not determined that well take on the ailments of our ancestors is a game changer. Professor Sebastiano estimates that as much as 70 per cent of our health outcomes come down to gene expression. Its the most important factor affecting our health from ageing and immunity, to even how we feel.

So our tempers can get longer and the wrinkles shorter; but how to get our genes to play ball in this radically-changed game? Well, the good news is that an awful lot of gene expression lies in our hands. Because our lifestyles the day-to-day of how we live can actually switch on/off those inherited traits. For example, exercise, stress, pollution, sleep and meditation can all impact genes as can behaviour towards others. One of the authors of that 2005 paper later found that simply performing small acts of kindness for other individuals can impact human gene regulation.

Gene expression is the most important factor affecting our health - from ageing and immunity, to even how we feel

As can connecting with nature, the alternative medicine guru Deepak Chopra told me when I was exploring on my sceptical BBC wellness podcast All Hail Kale how to somehow shift my genetic tendency towards being a morning person.

As can leaving earth. After astronaut Scott Kelly returned from the International Space Station, Nasa found his gene expression was seven per cent different from his identical twins.

But the single biggest way to impact gene expression with all the benefits that can have for mind, body, immunity, ageing etc is through what we eat. The nutrients we ingest go deep inside our cells, interact with DNA and can actually flip switches to turn genes on or off. Food as molecular medicine.

Studying the relationship between our diet and genes is a breakthrough branch of science called nutrigenomics. And its captivated me.

Seeing how something as natural and accessible as nutrients can affect this vital process of gene expression compelled me to go from cynic on the sidelines to, well, getting stuck in. To team up with the Stanford Professor Sebastiano and Dr Uma Naidoo Harvard Medical Schools pioneering nutritional psychiatrist to bring nutrigenomics research to the masses. Cards on the table, weve launched Karmacist the worlds first nutrigenomics-based supplement with formulations for Mood, Relax, Immunity and Energy. Weve always known that plants are powerful. Mankind has been turning to them for more than 60,000 years. Plants power an estimated 40 per cent of modern pharmaceuticals. But its geekily fascinating to use nutrigenomics to drill down deeper to see how and why botanicals might be working their magic.

Take saffron. The active components in this precious Persian spice have been found to help regulate the gene that transports serotonin the happy hormone thats key to our moods. Saffron has also been shown to increase the expression of the feel-good chemical dopamine in the brain. Indeed, Dr Naidoo notes, its been shown that Saffron is as effective as Prozac in decreasing depressive symptoms. Theres perhaps good reason now revealed by cutting-edge science why saffron has been coveted for millennia, and is pound for pound more expensive than gold.

Another ancient botanical yielding its cellular secrets is ashwagandha. Prized for its rejuvenating qualities in Ayurvedic tradition, research now shows how ashwagandha can prevent the expression of certain genes that can drive inflammation a known factor in stress and anxiety. Reishi mushrooms contain phytochemicals which, studies show, can help regulate the immune system.

That herbs and plants can have such deep, transformative potential also tallies with our understanding of the gut-mind link: the two-way highway running between brain and belly. Because, as Deepak Chopra told me, humans arent just carrying around their 25 thousand or so genes but another two million extra genes which are not human, they are bacteria. Technically-speaking, youre a few human genes hanging onto a bacterial colony which is known as the microbiome, or second genome, and its totally dependent on your lifestyle.

So, the way we live especially what eat doesnt just impact our own DNA, but the several million genes of the mass of bacteria were shlepping around that seems to have a direct line to our brains.

The nutrients we eat deeply impact our molecular and cellular processes - and directly affect mental health

Were still in the nascent days of nutrigenomics and in understanding precisely how the gut-mind axis works.

But at Massachusetts General Hospital, where Dr Uma Naidoo directs the USs first hospital-based Nutritional Psychiatry Service, she uses nutrients as part of her clinical practice and has no doubt about the mood-food connection. The nutrients we eat deeply impact our molecular and cellular processes and directly affect our brains and our mental health, Dr Naidoo says.

Psychiatry has been too slow to realise the rest of the body and what we feed it affects our moods and stability. Nutrition is the pioneering new frontier for better mental health and resilience.

With enough gene-expression-friendly nutrients along with meditation, exercise, sleep, and exposure to nature a grump-free future might beckon where waiters can take as long as they want, particularly if theyre bringing saffron risotto.

The benefits packed in herbs and spices are mind-blowing, says Harvard nutritional psychiatrist Dr Uma Naidoo. Were not just adding more flavour to our food these seasonings can be good for our moods too, she notes.

To help combat depression, Dr Naidoo suggests:

Oregano: research shows its active component has promising antidepressant activity and is likely to help protect brain tissue.

Saffron: the ultimate mood-enhancing spice (see main article for its serotonin and dopamine prowess).

Turmeric: shown in studies to adjust brain chemistry and protect cells against toxic damage that leads to depression, Dr Naidoo writes. Always add freshly ground pepper to maximise absorption.

Excerpt from:
How to hack your genes and eat your way younger - Evening Standard

Name: Emily Ozdowski

Position: Instructor in the Duke Department of Biology Meet Emily's Nominator

Emily was nominated by Dr. Sheila Patek, professor of Biology and one of Ozdowskis mentors.Emily exemplifies the very best of Duke. She is dedicated to undergraduate education and has tirelessly put student needs first throughout the pandemic. She gave tremendous effort and planning into teaching during the pandemic so that students could safely take lab classes in person - a lifeline for many students. No matter the setback and challenge, Emily has kept positive and constructive attitude - always finding a way to make things work and always supporting student learning, engagement, and growth. It has been an absolute privilege working with Emily and I hope we can express our Duke gratitude in the Blue Devil of the Week way!"

Years at Duke: 15

What she does at Duke: In high school in Ringgold, Virginia, Emily Ozdowski read an article about the genetics of schizophrenia in a Virginia Tech magazine and knew right away that she wanted to become a researcher.

That curiosity eventually landed her at Duke as a postdoctoral researcher in 2006.

Today, as an instructor in the Department of Biology, Ozdowski continues to ask important and interesting questions for the sake of her own research, while helping the next generation of researchers discover their passions in science.

Every spring semester, Ozdowski teaches a class that puts junior and senior-level undergraduates in the drivers seat of their own research projects, using zebrafish and mussels in the classroom to explore their interests. The students work with Ozdowski to determine the subject of their research, exploring topics such as climate change or the affect of chemicals excreted by the human metabolism into water sources on mussels.

I love the curiosity factor, Ozdowski said. The fact that we can brainstorm these amazing connections and look up all sorts of new information is a great way to learn to test a hypothesis with lab experiments. Whether its super focused on human health or ecology, in this lab, were able to ask some fun questions and go try to figure out the answer.

Outside the classroom, Ozdowksi works with Dr. Nina Sherwood to research Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP), a rare genetic neurological disorder that causes muscle weakness and tightness in the lower half of the body.

Using fruit flies, which have a similar gene to humans that causes the disorder, Ozdowski studies how neurons signal to muscles and how glial cells help make those developmental connections.

I wanted to do something that was both basic science but also could have human application, so the fruit fly really appealed to me all the way since undergrad and graduate school, she said.

Best advice received: Ozdowskis parents taught her that you have to find the places where youll be most happy. That became important when Ozdowski received her doctorate from the University of Virginia and contemplated what was next.

Ozdowski came to Duke, where shes been ever since.

When youre looking for either a school or a job or the next stage of life, having it be a good fit for you is just as important as prestige or money. I have been so lucky to find the things that fit my personality, she said. That is really important for happiness.

Something unique in her workspace: Working with fruit flies in her research, Ozdowski naturally has all sorts of insect-themed dcor in her office, including from attending many of the annual Drosophila Research Conferences, affectionately known in the field as The Fly Meeting.

My office has fruit fly postcard art, jewelry, ornaments, and toys that I've collected over the years, Ozdowski said. My daughter loves art and has given me paintings of insects to decorate my shelves.

What she loves about Duke: Ozdowskis favorite part of her job is interacting with students, who come from all over the country and world but whose curious and creative minds led them to her class.

She has the opportunity to encourage them to explore why science appeals to them.

I get to design the courses that I wish Id had, she said. So if theres something that I didnt get to do as an undergraduate, then its really fun to be able to have that freedom here.

When shes not at work, she likes to: Since she came to Duke in 2006, Ozdowski has enjoyed pickup volleyball at the outdoor court on East Campus with a group of faculty, staff, students and Durham residents.

Its a great group of friends and just friendly competition, she said.

Lesson learned during the pandemic:

Teaching lab-based classes during the pandemic has meant plenty of lessons in flexibility. With COVID-19 forcing quarantine, Ozdowski has had to learn to adjust her teaching, hold frequent makeup labs and instruct students while theyre socially distanced across two different classrooms.

Were all more flexible than we realize or we can be more flexible than we gave ourselves credit for before, Ozdowski said. Since the pandemic, it seems like almost all of the classes are more laid back. Weve all been forced to become resilient and flexible, so whatever happens were going to make it work.

Originally posted here:
Blue Devil of the Week: A Curious Researcher and Dedicated Teacher - Duke Today

In the United States, cardiovascular disease (CVD) is a major health problem accounting for nearly 40 percent of all deaths each year, according to the US National Library of Medicine. Now, scientists from University of Utah Health have confirmed that artificial intelligence (AI) can better predict cardiovascular disease, including risk factors, onset, and course.

Fortunately, several risk factors for heart diseasesuch as tobacco use, hypertension, obesity, elevated low-density lipoprotein cholesterol (LDL-C), and hypercoagulable states can be modified. Much like detecting cancer early, therapeutic lifestyle changes and drug treatment can be highly effective at reducing a patients risk of heart attack and stroke if risk factors can be identified in patients early. But AI technology could improve this process, with the potential of saving lives before adverse events occur.

The Centers for Disease Control and Prevention (CDC) lists heart disease as the #1 leading cause of death in the US, followed by cancer and Covid. Cardiovascular disease is a grave concern in the field of medicine. Here in Utah, University of Utah Health researchers have been working closely with physicians at Intermountain Primary Childrens Hospital to develop computational tools that accurately measure the combined effects of existing medical conditions on a patients heart and blood vessels.

While the initial research is limited to cardiovascular disease, its only the beginning. Researchers see the vast potential of AI technology and how it can essentially help identify and pinpoint risk factors in a broad range of medical diagnoses.

We can turn to AI to help refine the risk for virtually every medical diagnosis, [including] the risk of cancer, the risk of thyroid surgery, the risk of diabetesany medical term you can imagine, says Martin Tristani-Firouzi, the studys corresponding author, a pediatric cardiologist at U of U Health and Intermountain Primary Childrens Hospital, and scientist at the Nora Eccles Harrison Cardiovascular Research and Training Institute.

The current methods for calculating various risk factors on cardiovascular diseasessuch as medical history and demographicsare subjective and imprecise, says Mark Yandell, senior author of the study, professor of human genetics, and co-founder of Backdrop Health. Since these methods fall short, they fail to identify those interactions that can profoundly affect the health of a persons heart and blood vessels.

Instead, the researchers focused on measuring comorbidities and how they influence patient health. Yandell, Tristani-Firouzi, and their colleagues from Intermountain Primary Childrens Hospital and U of U Health sorted through more than 1.6 million anonymous electronic health records (EHRs) utilizing AI. These EHRs included detailed information about patients, including lab tests, diagnoses, medication prescribed, and medical procedures, which helped researchers identify which comorbidities were most likely to aggravate cardiovascular disease.

The important thing is that we can now calculate any outcome given multiple combinations of prior events in the patients medical record, Yandell says. This allows us to refine a patients risk for a medical diagnosis and understand how prior events influence future ones.

The researchers found that patients with a previous diagnosis of cardiomyopathy, a disease of the heart muscle, had an 86 times higher risk of needing a heart transplant than those without cardiomyopathy. Individuals with viral myocarditis had about a 60 times higher chance of needing a heart transplant. Transplant risk for those who used the drug milrinone (used to treat heart failure) rose by 175 timesthe strongest predictor of a heart transplant.

In certain cases, the combined risk was significantly higher. When individuals took milrinone and had cardiomyopathy, for instance, their risk of needing a heart transplant jumped to 405 times higher than individuals with healthier hearts.

This novel technology demonstrates that we can estimate the risk of medical complications with precision and even determine better medicines for individual patients, Josh Bonkowsky, director of the Primary Childrens Center for Personalized Medicine, told U of U Health.

Continue reading here:
This AI device is changing heart attack prevention - Utah Business - Utah Business

When talking about caribou, most people probably think of some version of Santa Clauss reindeer. Although real-life reindeer sadly do not exhibit any of the fantastical traits associated with helping Santa deliver gifts all over the world, caribou their North American counterpart of the same species (Rangifer tarandus) are in fact known to perform epic long-distance migrations.

Despite this, not everyone knows that not all caribou migrate caribou that live in boreal forests are indeed mainly sedentary. Things can get even trickier when we consider populations in which only some caribou migrate, a phenomenon called partial migration.

Why these behavioral differences exist is a fascinating research question, the answer to which is strategically important for the conservation of migratory animals, which are globally imperiled.

In a recently published study, we examined these two types of behaviors in western Canadian endangered caribou and linked a caribous tendency to migrate with its genetic heritage.

The main purpose of our study was to investigate whether caribou migratory behaviour is associated with genetics. To do this, we examined single nucleotide polymorphisms (SNPs), which are fragments of DNA increasingly used by researchers in genetic studies. SNPs are highly abundant and found in genes all across an organisms entire genetic makeup. This means that they are particularly suitable for studies aimed at determining the association between genetic, ecological and behavioural characteristics.

At first, these kinds of markers were used only for model species such as humans and mice, but thanks to recent technologies, they can now be obtained and analyzed in the context of wild species at a reasonable cost.

Our research group, based at the University of Calgary, studied migratory behaviour in 139 radio-collared caribou across western Canada. These caribou belonged to populations located in different environments, ranging from tundra to forests and mountains. We examined GPS locations for each animal using several approaches, including looking at an individual animals movement and seasonal ranges (the winter and summer areas where the animals live).

As a result, we were able to tell which animals were migratory and which were not, and determined that caribou in the tundra tend to be more migratory than others, performing the longest migration (up to 500 kilometres one way). These findings also supported previous studies.

Our first step was to examine SNPs and determine groups of individuals with similar genetic characteristics. For each of the 139 caribou we tracked, we obtained around 30,000 SNPs. Our caribou mainly belonged to either a northern or southern group, which is consistent with previous studies.

Historically, two caribou genetic lineages evolved in separated glacial refugia (areas without ice, where flora and fauna survived) located north and south of the ice sheet during the ice ages. The historical northern refugia was predominantly composed of tundra habitat, where caribou migrated to follow seasonally available food.

In contrast, the southern portion of the species range was dominated by forested environments, where caribou were sedentary as a consequence of reduced seasonality of resources. Our findings showed that that caribou belonging to the northern group were more likely to migrate, indicating that migration may be associated with the genetic ancestry of caribou.

We then wanted to know whether there were specific genetic mutations associated with migratory behaviour, and consequently identified 57 SNPs associated with migration. Many of these SNPs were found in genes that may influence migration in other species. These genes included those regulating including circadian rhythms, sleep, fat metabolism and hormone production.

Overall, our findings provide initial evidence of a package of ancestral genes common across migratory groups that affects the inclination to migrate.

Migratory animals are known to positively affect biodiversity and ecosystem functioning. Upon arrival at a destination site, migrants deposit nutrients and other substances into resident communities and ecosystems. This is being affected by human activities, and there have been resultant dramatic declines in the populations of migratory ungulates. The disappearance of migratory behaviour is now recognized as a global conservation challenge, with alarming new findings for threatened caribou in particular.

Human-caused habitat alterations and climate change have both contributed to caribou decline. This, alongside the local extinction of some populations of mountain caribou, could mean the disappearance of other ecological and genetic behaviours.

If, as we report, migratory behaviour is genetically influenced, caribou could be further impacted by the permanent loss of migratory behaviour. Migratory behaviour, as well as the set of mutations contributing to it, may not be easily re-established once lost.

Genetic mutations, especially those that are beneficial, occur in evolutionary timeframes that are incompatible with the fast decline of caribou. In the face of rapid declines, novel mutations, including those influencing migration, are unlikely to emerge.

This loss could perhaps be averted with the maintenance of seasonal habitats for caribou a strategy that would facilitate migration and give caribou a better fighting chance at population persistence.

See more here:
Whether caribou migrate or stay put is determined by genes that evolved in the last ice age - The Conversation Indonesia

NEW YORK--(BUSINESS WIRE)--Kallyope, Inc., a leading biotechnology company focused on identifying and developing therapeutics involving the gut-brain axis, today announced the appointments of George Shiebler as General Counsel and Anita Kawatra as Executive Vice President, Corporate Affairs, to help steer the company as it advances a pioneering drug discovery platform, clinical trials, and pipeline of multiple programs mediated by gut-brain axis signaling across a broad range of therapeutic areas.

With novel compounds in two lead programs now in clinical development, this is an inflection point for Kallyope. As we embark upon our next phase of growth to bring forth powerful new therapeutics driven by our unique drug discovery platform, we are continuing to build a world-class team to help take our work from the lab to the real world, said Jay Galeota, president and CEO, Kallyope. George and Anita are recognized industry leaders with extraordinary track records. George brings to Kallyope comprehensive knowledge of pharmaceutical industry regulations and unmatched expertise in negotiating a wide variety of sophisticated corporate transactions. Anita has an extensive background in the life sciences, global public health, and public policy, with a strong history of success advising management and boards of startup and growing biotech companies. We look forward to benefiting from their experience and perspectives as we move forward.

George Shiebler has more than 30 years of experience as an attorney in the pharmaceutical and biotech industries. Most recently, he was Senior Vice President and General Counsel of nference, an AI-driven health technology company. Previously, he was a founding executive and General Counsel at Inheris Biopharma, and General Counsel and Chief of Staff for G&W Laboratories. Mr. Shiebler spent 23 years at Merck & Co., leading the worldwide transaction and licensing practice and overseeing multibillion-dollar public and private mergers and acquisitions, multinational joint ventures, and venture investments in startups. He holds a JD from the University of Georgia School of Law, where he was a member of the Law Review, and a bachelors degree from the University of Virginia.

Anita Kawatra has held numerous senior management positions in the life sciences over the past 20 years, following a decade in government and policy. Most recently, she was Chief Corporate Affairs Officer at nference. Previously, she was a founding executive of Inheris Biopharma and held global roles at Elan Pharmaceuticals, Prothena Biosciences, Merck & Co., and the International AIDS Vaccine Initiative. Prior to her work in biopharmaceuticals, she served in the administrations of New York City Mayor David Dinkins and New York Governor Mario Cuomo. Ms. Kawatra is a board member of the New York City Health and Hospitals Corporation, the largest public health system in the United States. In 2020, she was named among the 100 most influential Asian Americans in New York politics and policy. She holds a masters degree from Columbia University and a bachelors degree from Yale University.

About Kallyope

Kallyope, headquartered at the Alexandria Center for Life Science in New York City, is a biotechnology company dedicated to unlocking the therapeutic potential of the gut-brain axis. The companys cross-disciplinary team integrates advanced technologies in sequencing, bioinformatics, neural imaging, cellular and molecular biology, and human genetics to provide an understanding of gut-brain biology that leads to transformational therapeutics to improve human health. The companys founders are Charles Zuker, Ph.D., Lasker Award winner Tom Maniatis, Ph.D., and Nobel laureate Richard Axel, M.D. For more information visit http://www.kallyope.com.

Excerpt from:
Kallyope, Pioneers in Drug Discovery via the Gut-Brain Axis, Strengthens Senior Leadership Team with Key Appointments - Business Wire

Cyprium Therapeutics, a subsidiry of Fortress Biotech, is developing CUTX-101 for the treatment of Menkes disease

CUTX-101 has potential to be first FDA-approved treatment for Menkes disease; rolling submission of New Drug Application to FDA is ongoing and expected to be completed in mid-year 2022

MIAMI and SOLANA BEACH, Calif., March 21, 2022 (GLOBE NEWSWIRE) -- Cyprium Therapeutics, Inc. (Cyprium), a Fortress Biotech, Inc. (Nasdaq: FBIO) (Fortress) subsidiary, with support from its licensing partner Sentynl Therapeutics, Inc. (Sentynl), a wholly owned subsidiary of Zydus Lifesciences Ltd. (formerly known as Cadila Healthcare Ltd.), today announced positive data on CUTX-101, copper histidinate (CuHis), in patients with Menkes disease. The data will be presented as a Top-Rated Abstract and Poster at the 2022 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting taking place March 22-26, 2022, virtually and at Music City Center in Nashville, TN. The previously reported results are from an efficacy and safety analysis of data integrated from two completed pivotal studies in patients with Menkes disease treated with CUTX-101.

Details of the poster are as follows:

Poster Title: Safety and Efficacy of Copper Histidinate (CUTX-101) Treatment for Menkes Disease Caused by Severe Loss-of-Function Variants in ATP7APoster Number: eP195Authors:Stephen G. Kaler, M.D., M.P.H., Shama Munim, M.S., Michael Chen, Ph.D., Robert Niecestro, Ph.D., Lung S. Yam, M.D., Ph.D.Dates / Times: Posters will be available for viewing on Wednesday, March 23, 5:00 p.m. 7:00 p.m., Thursday, March 24, 9:30 a.m. - 4:30 p.m. and Friday, March 25, 10:00 a.m. 1:00 p.m. in the Exhibit Hall. Dr. Kaler will formally present the poster on Thursday, March 24 from 10:00 a.m. 11:30 a.m. CT.

The abstract can be viewed here.

The positive data that will be presented at the 2022 ACMG Annual Clinical Genetics Meeting demonstrate the efficacy and safety of CUTX-101 and its potential to be the first treatment approved by the U.S. Food and Drug Administration (FDA) for patients with Menkes disease. We continue to make progress with our rolling submission of a new drug application (NDA) for CUTX-101 which we anticipate to be completed in the middle of this year, said Lung S. Yam, M.D., Ph.D., President and Chief Executive Officer of Cyprium. We welcome the opportunity to present the positive efficacy and safety data of CUTX-101 to medical geneticists who are often involved in the diagnosis and treatment of Menkes disease, a rare, fatal pediatric disease.

In 2021, Cyprium partnered with Sentynl Therapeutics, Inc., a U.S.-based specialty pharmaceutical company owned by the Zydus Group, to bring CUTX-101 to market. Cyprium will retain development responsibility of CUTX-101 through approval of the NDA by the FDA, and Sentynl will be responsible for commercialization of CUTX-101 as well as progressing newborn screening activities.

About Menkes Disease Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of copper transporter ATP7A. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment (Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7A-related disorders based on the Genome Aggregation Database (gnomAD). Molecular Genetics and Metabolism Reports 2020 June 5;24:100602). The condition is characterized by distinctive clinical features, including sparse and depigmented hair (kinky hair), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying before the age of three years old. Milder versions of ATP7A mutations are associated with other conditions, including Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy. Currently, there is no FDA-approved treatment for Menkes disease and its variants.

About CUTX-101 (Copper Histidinate)CUTX-101 is in clinical development to treat patients with Menkes disease. CUTX-101 is a subcutaneous injectable formulation of Copper Histidinate manufactured under current good manufacturing practice (cGMP) and physiological pH. In a Phase 1/2 clinical trial conducted by Stephen G. Kaler, M.D., M.P.H., at the National Institutes of Health (NIH), early treatment of patients with Menkes disease with CUTX-101 led to an improvement in neurodevelopmental outcomes and survival. In August 2020, Cyprium reported positive topline clinical efficacy results for CUTX-101, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment (ET) with CUTX-101, compared to an untreated historical control cohort, with a nearly 80% reduction in the risk of death. CUTX-101 has been granted FDA Breakthrough Therapy, Fast Track, Rare Pediatric Disease and FDA Orphan Drug Designations. Additionally, the European Medicines Agency granted Orphan Drug Designation for CUTX-101. A Cyprium-sponsored expanded access protocol for patients with Menkes disease is ongoing at multiple U.S. medical centers.

About Cyprium TherapeuticsCyprium Therapeutics, Inc. (Cyprium) is focused on the development of novel therapies for the treatment of Menkes disease and related copper metabolism disorders. In March 2017, Cyprium entered into a Cooperative Research and Development Agreement (CRADA) with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the NIH, to advance the clinical development of CUTX-101 (Copper Histidinate injection) for the treatment of Menkes disease. In addition, Cyprium and NICHD entered into a worldwide, exclusive license agreement to develop and commercialize adeno-associated virus (AAV)-based gene therapy, called AAV-ATP7A, to deliver working copies of the copper transporter that is defective in patients with Menkes disease, and to be used in combination with CUTX-101. CUTX-101 was granted FDA Breakthrough Therapy, Fast Track and Rare Pediatric Disease Designations, and both CUTX-101 and AAV-ATP7A have received FDA Orphan Drug Designation previously. Additionally, the European Medicines Agency previously granted Orphan Drug Designation to CUTX-101. Cyprium was founded by Fortress Biotech, Inc. (Nasdaq: FBIO) and is based in New York City. For more information, visit http://www.cypriumtx.com.

About Fortress BiotechFortress Biotech, Inc. (Fortress) is an innovative biopharmaceutical company focused on acquiring, developing and commercializing high-potential marketed and development-stage drugs and drug candidates. The company has nine marketed prescription pharmaceutical products and over 30 programs in development at Fortress, at its majority-owned and majority-controlled partners and at partners it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is driven by a world-class business development team that is focused on leveraging its significant biopharmaceutical industry expertise to further expand the companys portfolio of product opportunities. Fortress has established partnerships with some of the worlds leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including AstraZeneca plc, City of Hope, Fred Hutchinson Cancer Research Center, St. Jude Childrens Research Hospital, Nationwide Childrens Hospital and Sentynl Therapeutics, Inc. For more information, visitwww.fortressbiotech.com.

About Sentynl TherapeuticsSentynl Therapeutics is a U.S.-based biopharmaceutical focused on bringing innovative therapies to patients living with rare diseases.The company was acquired by the Zydus Group in 2017. Sentynls highly experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is committed to the highest ethical standards and compliance with all applicable laws, regulations, and industry guidelines. For more information, visit http://www.sentynl.com.

About Zydus The Zydus Group, with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global pharmaceutical company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 23000 people worldwide and is driven by its mission to unlock new possibilities in life-sciences through quality healthcare solutions that impact lives. The group aspires to become a global life-sciences company transforming lives through pathbreaking discoveries. For more information, visit https://www.zyduslife.com/zyduslife/

Forward-Looking StatementsThis press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended. As used below and throughout this press release, the words we, us and our may refer to Fortress individually or together with one or more partner companies, as dictated by context. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; risks relating to the timing of starting and completing clinical trials, including the possible disruption of trials due to the hostilities in Europe; our dependence on third-party suppliers; risks relating to the COVID-19 outbreak and its potential impact on our employees and consultants ability to complete work in a timely manner and on our ability to obtain additional financing on favorable terms or at all; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our Securities and Exchange Commission filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The information contained herein is intended to be reviewed in its totality, and any stipulations, conditions or provisos that apply to a given piece of information in one part of this press release should be read as applying mutatis mutandis to every other instance of such information appearing herein.

Company Contacts:Jaclyn Jaffe and William BegienFortress Biotech, Inc.(781) 652-4500ir@fortressbiotech.com

Lung Yam, M.D., Ph.D.Cyprium Therapeutics, Inc. ir@cypriumtx.com

Michael HerczSentynl Therapeutics, Inc. ir@sentynl.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Fortress Biotech, Cyprium Therapeutics and Sentynl - GlobeNewswire