Category Archives: Genetic medicine

When the Smithsonian National Museum of Natural History opened its genomics exhibit in 2013, the field was just celebrating the 10th anniversary of the completed Human Genome Project. Sequencing that first genome cost over $500 million. The genomes since cost $10,000.

In 2022, as the museum prepares to wrap up the landmark exhibit, much has changed. Gene names such as BRCA1 and HER2 have entered the public consciousness. Sequencing DNA has become faster, cheaper, and smaller-scale. Portable sequencers that were not even being sold commercially in 2013 have since been used to trace the evolution of the Ebola virus as it wreaked havoc in West Africa. The development of CRISPR-Cas9 landed a Nobel Prize. The cost of genome sequencing is rapidly approaching $100.

What seemed cutting edge maybe in 2013, now in 2022, were just things that were somewhat more routine, said Carla Easter, who helped organize the exhibit while at the National Human Genome Research Institute, which partnered with the Smithonian to launch the project.

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Nobody knew what CRISPR was ten years ago, added Easter, now at the Smithsonian. But now, people will mention it and theyll know what that is. They may not know understand the science behind it, but at least theyve heard the word.

Before the exhibit closes its doors later this year, STAT spoke with curators, educators, and leading scientists involved in its creation about how genomics has changed in the past decade.

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The field of genomics has gone way beyond genomics experts, people who would call themselves genomicists, and its applied everywhere, said Lawrence Brody, who leads the NHGRI Division of Genomics and Society. Weve done these analyses of the NIH budget, and theres way more genomics being done outside of our institute than there is inside our institute, because its such a powerful tool. And thats a great thing.

Most of those improvements have been with sequencing, he said. Were now talking about what genetic variation might be. If you study people who have a disease, [and] find a genetic variant that seems to be common in those people, you dont really know anything until you ask yourself, How common is that variant in people who dont have the disease? And you need to look at large numbers of people to understand that. This also means involving people who are not normally represented in research, a task the NIH-funded All of Us program has taken up.

Another change he sees is the newfound ability to broadly study the entire genome, rather than only specific genes, and to analyze how various parts of the genome are being turned on or off in individual cells.

Even though all cells but sperm and egg share the same genome, they do not all make the same proteins. A decade or two ago, studying these differences involved an arduous process, and scientists could only study a few specific genes at a time. But Brody said that has changed thanks to advances in RNA sequencing, which allow you to ask questions about all the genes completely, objectively, and agnostically. And to me, thats really the power and has always been the power of genetics is to ask the question and have the organism tell you whats important, as opposed to guess and saying It must be this gene or it must be that gene.

Now, he said, the field needs to understand how diseases are caused by a combination of genes and environmental exposures, manipulate the genome to treat diseases, and survey life on the planet because, as a geneticist, its really important for me to know the variations out there.

We often say Oh, in ten years, well be doing this, and if you look back at those predictions, were wrong a lot, said Brody. But we will get there.

To Stephen Palumbi, a professor of marine sciences at Stanford who studies corals, the biggest change in genomics is the speed and cost of sequencing.

The same questions are there, the same approaches are there, said Palumbi. But its like you took a garden hose that you were plenty of water flow and everything and you turned it into a firehose of information. That deluge of data that you can get right now is incredible. So the whole field, not just natural history or oceans, but the whole field of genomics, has become more and more and more tuned to being a high-flow data-rich, incredible science of whats now called bioinformatics. Bioinformatics at the time, a decade ago, was really important. Its probably increased in importance 50-fold because the data sets have increased 100-fold, and being able to actually pull information out of these data sets has become one of the most interesting, challenging, and rewarding parts of how genomes are used.

The human genome is the most traveled, well-mapped genome in the known universe, no big surprise. But I study organisms that are not humans and have genomes anyway. And so were always sort of scrambling a little bit behind that technology, but adopting it and adapting it, he said.

He pointed to work he is doing to study corals living on reefs in an archipelago in Palau that look strikingly similar, but have turned out to be genetically different. Being able to deeply mine the genomes of those corals offers valuable clues about their genetic capacity to adapt to environmental change.

So genomics gives me a map to their current patterns of adaptation that I would not get in any other way, he said. When this exhibit opened, I couldnt have done what I just told you because it would have been prohibitively expensive. And the people who can do the bioinformatics really werent there. And the genetic, genomic resources that I need to do this work werent there. But theyre there now. So thats where the whole field has changed so much. In that period of time, 2011 till now, the entire landscape, seascape, forestscape changed.

He said the fields advances like enabling handheld sequencing will make it even easier to reveal DNA in the environment, whether that is samples pulled from a kelp forest or fungus living in the soil of wetlands. Those insights are more critical than ever, as they can offer insights on monitoring pathogens and endangered species.

What I dont want to see in 50 years in a genome exhibit, is a whole lot of genomes of extinct species that weve lost because of climate change.

Harvard professor and genetics pioneer George Church was involved in the Human Genome Project from its earliest days, having joined the effort in 1984, years before the National Institutes of Health got involved. He saw the project pique the interest first of lawmakers, and then the public at large. Some projects that are highly technical, whether theyre expensive or not, are unpopular or ignored, said Church. But this one actually captured Congresss interest, around 1987 was really when they started paying attention. They liked this and they committed to $3 billion, which was quite a lot in 1987. And then they proceeded to get excited in all kinds of science and they ended up doubling the NIH budget, which is almost unprecedented and hasnt happened since then.

And despite the celebration of the sequencing of the human genome, Church said, the work is far from over.

[It] had been sort of declared done in 2001, and then was re-declared done in 2004. And its actually still not done in my opinion. This year marks the first year that weve finished one genome, one human genome, but in a way that really isnt generally applicable we did it to a haploid cell. Haploid cells have only a single set of chromosomes, in contrast to the typical human cell which is diploid and has two. So if you want to diagnose a patient, you have to be able to do a diploid genome. And no ones ever completed a diploid genome yet, although we are on our way, Church said.

Church said genomics has already made an impact in medical care. It played a role in the development of the Covid-19 vaccines, and can give prospective parents insight about when they carry a recessive gene for certain diseases. It also enabled the development of the first gene therapy to be approved by the Food and Drug Administration. Even when the exhibit was being developed a decade ago, he said, the idea of gene therapy wasnt that popular. In fact, it just barely was recovering from its 2001 setback, or 1999 to 2001 setbacks, plural.

In the future, Church would like to see a bioweather map that uses genomics to keep tabs on and track the evolution of viruses and bacteria, akin to a weather forecast. What flu just flew in the town? And what is happening at the daycare? Should you take your kid? he asked.

But for all his big ideas about genomics, Church also has his sticking points. Among them: One of my pet peeves is when people say, Oh, you know that humans share fill in your favorite number with fill in your favorite organism. So itd be like 46% related to plants or bananas, he said. I mean, its a completely meaningless statistic.

(It is a battle he did not win with the Smithsonian exhibit, which tells viewers that the human genome is 41% similar to a bananas.)

For Joann Boughman, a senior vice chancellor at the University System of Maryland, advances in genomics have changed how people perceive genetic diseases. From the historical perspective, if you will, in human genetics, we have understood and have always looked at variability as an essential theme, said Boughman. It wasnt until the human genome started and people started understanding about the variations at the DNA level that they made the connection between genes and ultimate phenotype, what we look like. And it has been really fascinating to see how these two worlds, as you will, collide and hopefully come together.

During the pandemic, Boughman served as the point person for the Maryland university systems Covid response, which included a community of over 200,000 students, staff, and faculty. And I realize Im working with an educated population, but all kinds of people really understood when we started talking about viral variants, they understood what had changed was the DNA in the virus, that there had been a mutation. These were not absolutely foreign concepts to people, and they, with very little explanation, would understand why one vaccine might fight this virus, but not a mutated form of that virus, Boughman said.

This is part of a growing awareness she had seen unfolding long before the pandemic hit. The fact that the double strand of DNA is not a foreign concept, even to relatively small children, really makes our conversation different. And thats been an incredible thing to watch over the last 40 years. Today, if people see an image of DNA, theyll recognize it.

Boughman said that shift struck her recently when she saw a commercial for a treatment for a rare genetic disease. It hit me right between the eyes that they actually have an ad on TV and named a genetic syndrome and talked about that drug that was helping these children. But 20 years ago, the idea of putting on television a picture of a child who has physical abnormalities and labeling them as having a genetic disease or a genetic syndrome just would have been devastating. But now that we are getting to the point where we understand enough about the genetics that we can start to intervene and treat, it becomes a very different perspective than somebody who is simply doomed. They labeled it genetic and they labeled it as a syndrome, and then they talked about hope that they had. And that simply was not the case 20 or 30 years ago, at all.

As a geneticist and professor at the University of Pennsylvania, Sarah Tishkoff originally got involved in the exhibit to share her expertise on what genetics and genomics can tell us about the evolutionary history of humans. Given her research, she is keenly aware of how much the field has changed in the past few decades.

She is also aware of how far the field still needs to go specifically when it comes to securing better representation in genomics research, which is overwhelmingly centered on white and European populations. What we dont really have are good reference genomes, she said. So there are populations or people in different parts of the world that might have insertions or deletions in their genome or things that arent even in that reference.

But if the Smithsonian were to open the exhibit again in 50 years, she said, we will have unraveled far more mysteries and the public will be far more familiar with the science.

I think at that point, most people are going to have their genome sequenced, she said. That would give scientists a far deeper trove of data to understand structural variation large-scale differences across the DNA of individuals, including duplications of certain genes and, in turn, knowledge of how humans have adapted to different environments and develop different levels of risk for disease. She added that by that time, were going to know more about what the genome variation actually does, similar to her findings that multiple different gene mutations can cause lactose tolerance.

She is also hopeful that we will have wide-ranging insights into ancient DNA and the origins of human history, including a far more complete picture. Right now, she noted, we are limited by the fact that ancient DNA is often poorly preserved. Someday, somebody is going to get ancient DNA from a fossil in Africa thats 50,000 years old or 100,000 or 200,000. Thats going to really help shed light on human history in that region, which is where we all evolved, Tishkoff said. Im hoping that were going to know a lot more examples of how people adapted to different environments.

In addition to his day job at the E.O. Wilson Biodiversity Foundation, Dennis Liu serves on the board of the American Chestnut Foundation, which has funded efforts to introduce a gene into American chestnut trees that can help them resist a group of diseases known as blight. To Liu, there are clear benefits that advances in genomics can bring to conservation efforts like this one.

But as the field ages, he also sees a downside to the growing distance from the Human Genome Project.

When the initiative launched, Liu said, there was a sense of a moonshot at the time. And I think that kind of new excitement isnt necessarily here. I havent done a survey or a poll, but I imagine that these things are now kind of all lumped together with big pharma and the pharmaceutical industry and sort of high-tech medicine. And I would imagine that a lot of people still would wonder, Oh, I dont know, what does this do for me? I do think theyd hope, of course, that this kind of information is going to help cancer treatments, for example, and those sorts of things.

For example: To the field, the increase in sequencing speeds is a huge advance. But I dont think that means much of anything to the general public, Liu said. Instead of feeling that genomics completed with the sequencing of the genome, he hopes we will continue to wonder about genomics. It is not like Oh, the genome, we did that, its over. Its like, No, its both that this work has continued and it continues to matter, said Liu, who was then with the Howard Hughes Medical Institute, And you should know something about it even if youre not a professional scientist.

Eric Green has served as the director of the NHGRI since 2009. The biggest difference he sees in genomics then, and genomics now? At the time I started as director, when this exhibition was being created, there was a lot of clarity around what had been accomplished and a lot of growing knowledge about how the human genome works. But the idea of actually using genomic information for the practice of medicine was pretty hypothetical.

When he stepped into his role, he wanted to close that gap and figure out how to use genomic information to improve the practice of medicine. And the biggest difference between then and now is then it was hypothetical and, while it is certainly not pervasive in medicine, there are a number of just very clear areas where now genomics is mainstream. Green highlighted the use of genomics to diagnose rare diseases. They were like the very first home runs in those areas, he said. But now its just routine practice. Another notable change, he added, is the proliferation of DNA genealogy tests from companies such as 23andMe and Ancestry.

Looking ahead, Green said he is a realist about the role of genomics in medicine.

The implementation of some aspects of genomic medicine are no longer scientifically difficult. Theyre sociological, because of the societal challenges associated with health care, said Green, who trained as a physician-scientist. What I would say going forward is that, Im actually quite optimistic were going to figure out a lot of these really valuable uses of genomics. But I cant claim to be as optimistic about the effective use of those tools in health care, because we all appreciate that health care is really complicated.

It is a hurdle he had not considered early on in research, he said. Science drives some things, but its not the only thing.

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As the Smithsonian wraps a genome exhibit, leaders in the field reflect - STAT

A large number of people are currently contracting COVID-19. Fortunately, most of them are experiencing only mild symptoms, largely thanks to the high vaccination rate. However, in some individuals the disease takes a much more severe cause and our understanding about the underlying reasons is still insufficient. The human genome may hold a key to why COVID-19 is more serious for some people than others. A team of scientists from the Berlin Institute of Health at Charit (BIH) together with colleagues from the United Kingdom and Canada have found genes and proteins that contribute to a higher risk of severe COVID-19. Their findings have now been published in the journal Nature Communications.

Doctors and scientists around the world are still in the dark as to why some people become severely ill when infected with SARS-CoV-2 (the virus that causes the COVID-19 disease), while others experience only mild symptoms. A team of scientists at the BIHs Digital Health Center has identified genes that - in addition known risk factors such as age and sex predispose people to experience a more serious infection.

It has been observed relatively early on that susceptibility to infection depends on a persons blood group, for example, which is inherited, explains Maik Pietzner, the studys lead author. So it was clear that the course of the disease is at least in part determined by genetics. Scientists at the BIH were given access to genetic data that researchers had collected from COVID-19 patients worldwide, which also included disease severity. At the time, there were some 17 genomic regions observed to be associated with a higher risk of severe COVID-19, Pietzner explains, but the causal genes and underlying mechanism remained unknown for many.

The Computational Medicine Group at BIH had previously developed a proteogenomic approach to link protein-encoding regions of DNA to diseases via the protein product. They applied this method to COVID-19 and came across eight particularly interesting proteins in this new study. One of these was a protein responsible for an individuals blood group, Claudia Langenberg, head of the Computational Medicine Group, explains. We were aware that this gene was associated with the risk of infection, so it was like a proof of concept. The protein ELF5, meanwhile, seemed like it could be much more relevant. We found that COVID-19 patients carrying a variant in the gene that encodes ELF5 were more much more likely to be hospitalized and ventilated, in some cases even died so we took a closer look.

The team turned to their colleagues from the Intelligent Imaging Group, led by Christian Conrad, because of their expertise in single-cell analyses. Lorenz Chua, a doctoral student in the group was immediately enthusiastic to find out which cells displayed a particular abundance of the ELF5 protein: We found that ELF5 is present in all surface cells of the skin and mucous membranes, but is produced in particularly large quantities in the lungs. Since this is where the virus causes most of its damage, this seemed very plausible.

But Conrad puts a damper on any hopes that the scientists may have identified a new target molecule for drug development: ELF5 is what is known as a transcription factor, and controls how frequently or infrequently other genes are switched on and off throughout the body, he explains. Unfortunately, it is difficult to imagine interfering with this protein in any way, as that would undoubtedly cause many undesirable side effects.

However, the scientists did identify another interesting candidate among the eight suspects: the protein G-CSF, which serves as a growth factor for blood cells. They found that COVID-19 patients who genetically produce more G-CSF tend to experience a milder disease course. Synthetic G-CSF has been available as a drug for a long time, so its use as a treatment for COVID-19 patients could be conceivable.

Translation of such genetic discoveries into clinical application is not an easy or rapid process. The work only possible through the support of many scientists and clinicans of the BIH and Charit, and open access results from studies around the world highlights how open science and an international team effort can step by step uncover how the smallest changes in our genetic make-up alter the course of disease, COVID-19 in this example. We started with global data from 100,000 participants and ended up looking at single molecules in individual cells. We believe that collaborations that allow us to rapidly move from the bigger picture and studying large populations to in depth molecular follow-up can help to better understand the clinical consequences of this virus and teach us important lessons for future pandemics, Pietzner concludes.

Maik Pietzner, Robert Lorenz Chua, Christian Conrad, Claudia Langenberg: ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19 Nature Communications (2022), DOI: 10.1038/s41467-022-31999-6

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About the Berlin Institute of Health at Charit (BIH)The mission of the Berlin Institute of Health at Charit (BIH) is medical translation: transferring biomedical research findings into novel approaches to personalized prediction, prevention, diagnostics and therapies and, conversely, using clinical observations to develop new research ideas. The aim is to deliver relevant medical benefits to patients and the population at large. As the translational research unit within Charit, the BIH is also committed to establishing a comprehensive translational ecosystem one that places emphasis on a system-wide understanding of health and disease and that promotes change in the biomedical translational research culture. The BIH was founded in 2013 and is funded 90 percent by the Federal Ministry of Education and Research (BMBF) and 10 percent by the State of Berlin. The founding institutions, Charit Universittsmedizin Berlin and Max Delbrck Center for Molecular Medicine in the Helmholtz Association (MDC),were independent member entities within the BIH until 2020. Since 2021 the BIH has been integrated into Charit as its so-called third pillar. The MDC is now the Privileged Partner of the BIH.

Contact

Dr. Stefanie SeltmannHead of CommunicationsBerlin Institute of Health at Charit (BIH)stefanie.seltmann(at)bih-charite.de

+49 (0)30 450 543019www.bihealth.org

Nature Communications

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Why some people suffer more from COVID-19 than others - EurekAlert

LogicBio Therapeutics, Inc. (NASDAQ:LOGC Get Rating) Equities researchers at William Blair boosted their Q3 2022 earnings per share (EPS) estimates for shares of LogicBio Therapeutics in a report issued on Tuesday, August 16th. William Blair analyst R. Prasad now expects that the company will post earnings per share of ($0.20) for the quarter, up from their previous forecast of ($0.25). William Blair has a Outperform rating on the stock. The consensus estimate for LogicBio Therapeutics current full-year earnings is ($0.88) per share. William Blair also issued estimates for LogicBio Therapeutics Q4 2022 earnings at ($0.22) EPS, Q4 2022 earnings at ($0.22) EPS, FY2022 earnings at ($0.77) EPS, FY2022 earnings at ($0.77) EPS, Q1 2023 earnings at ($0.32) EPS, Q2 2023 earnings at ($0.32) EPS, Q2 2023 earnings at ($0.32) EPS, Q3 2023 earnings at ($0.33) EPS, Q4 2023 earnings at ($0.34) EPS, Q4 2023 earnings at ($0.34) EPS, FY2023 earnings at ($1.29) EPS and FY2023 earnings at ($1.29) EPS.

LogicBio Therapeutics stock opened at $0.40 on Thursday. The stock has a market cap of $13.18 million, a PE ratio of -0.43 and a beta of 1.60. The company has a quick ratio of 2.74, a current ratio of 2.26 and a debt-to-equity ratio of 0.17. The businesss 50-day moving average price is $0.43 and its two-hundred day moving average price is $0.55. LogicBio Therapeutics has a 12-month low of $0.34 and a 12-month high of $5.15.

A number of hedge funds and other institutional investors have recently made changes to their positions in LOGC. Blair William & Co. IL acquired a new position in shares of LogicBio Therapeutics in the fourth quarter worth approximately $51,000. Samlyn Capital LLC lifted its stake in LogicBio Therapeutics by 2.5% in the fourth quarter. Samlyn Capital LLC now owns 1,511,417 shares of the companys stock valued at $3,492,000 after buying an additional 37,309 shares during the period. Acadian Asset Management LLC acquired a new position in LogicBio Therapeutics in the first quarter valued at approximately $32,000. Renaissance Technologies LLC acquired a new position in LogicBio Therapeutics in the first quarter valued at approximately $312,000. Finally, Virtu Financial LLC increased its holdings in shares of LogicBio Therapeutics by 312.4% during the first quarter. Virtu Financial LLC now owns 71,475 shares of the companys stock valued at $49,000 after acquiring an additional 54,145 shares in the last quarter. 55.20% of the stock is owned by institutional investors and hedge funds.

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LogicBio Therapeutics, Inc, a genetic medicine company, focuses on developing and commercializing genome editing and gene therapy treatments using its GeneRide and sAAVy platforms. The company's GeneRide technology is a new approach to precise gene insertion harnessing a cell's natural deoxyribonucleic acid; and gene delivery platform, sAAVy is an adeno-associated virus, which is designed to optimize gene delivery for treatments in a range of indications and tissues.

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Q3 2022 Earnings Forecast for LogicBio Therapeutics, Inc. Issued By William Blair (NASDAQ:LOGC) - Defense World

image:Picture depicting Micro-organospheres (MOS) encapsulating primary tissue derived cells prior to demulsification. view more

Credit: Terasaki Institute for Biomedical Innovation

(LOS ANGELES) A team of scientists, led by Xiling Shen, Ph.D., Chief Scientific Officer, and Professor at the Terasaki Institute for Biomedical Innovation (TIBI), has reached new levels in patient model development. They have developed improved methods for generating micro-organospheres (MOS) and have shown that these MOS have superior capabilities for a variety of clinical uses. As documented in a recent publication in Stem Cell Reports, their MOS can be used as patient avatars for studies involving direct viral infection, immune cell penetration and high-throughput therapeutic drug screening, something that is not obtainable with conventional patient-derived models.

Dr. Shens team has developed emulsion microfluidic technology for creating MOS, tiny, nanoliter-sized basal membrane extract (BME) droplets composed of tissue cell mixtures which can be generated at a rapid pace from an automated device. After the droplets are created, excess oil is removed by an innovative membrane demulsification process, leaving behind thousands of viscous, uniformly sized droplets which contain tiny 3D tissue structures.

The team went on to demonstrate unique MOS capabilities and features in several first-of-its-kind experiments. They were able to show that the MOS could be created from a variety of different tissue sources and the resultant MOS had retention of histopathological morphology, capacity for differentiation and genetic expression, and the ability to be frozen and sub-cultured, as in conventional organoids.

Experiments were conducted to test the ability to infect MOS with viruses. Unlike with conventional organoids, MOS can be directly infected with viruses without the removal and suspension of cells from its surrounding BME scaffold, hence recapitulating the process of viral infection of the host tissue. Dr. Shens team was able to create a MOS atlas of human respiratory and digestive tissues from patient autopsies and infect them with SARS-COV-2 viruses, followed by drug screening to identify drugs that block viral infection and replication within those tissues.

MOS also provide a unique platform for studying and developing immune cell therapy. Within natural diffusion limit of vascularized tissue, tumor-derived MOS allowed sufficient penetration by therapeutic immune T-cells such as CAR-T, enabling a novel T cell potency assay to assess tumor killing by the engineered T-cells. Such a model would be highly useful in investigating tumor responsiveness and in developing anti-tumor immune cell therapies.

MOS could be further integrated with deep-learning imaging analysis for rapid drug testing of small and heterogeneous clinical tumor biopsies. Moreover, the algorithm was able to distinguish cytotoxic vs. cytostatic drug effects and drug-resistant clones that will give rise to later relapse. This groundbreaking capability will pave the way for MOS to be used in the clinic to inform therapeutic decisions.

Dr. Shen and his team continue to refine and improve upon the MOS technology and to spotlight its versatility, not only as a physiological model for screening potential personalized treatments, but for disease studies and a variety of other applications as well, said Ali Khademhosseini, Ph.D., TIBIs Director and CEO. It looks to be the wave of the future for precision medicine.

Authors are: Zhaohui Wang, Matteo Boretto2, Rosemary Millen, Naveen Natesh, Elena S. Reckzeh, Carolyn Hsu, Marcos Negrete, Haipei Yao, William Quayle, Brook E. Heaton, Alfred T. Harding, Else Driehuis, Joep Beumer, Grecia O. Rivera, Ravian L van Ineveld, Donald Gex, Jessica DeVilla, Daisong Wang, Jens Puschhof, Maarten H. Geurts, Shree Bose, Athena Yeung, Cait Hamele, Amber Smith, Eric Bankaitis, Kun Xiang, Shengli Ding, Daniel Nelson, Daniel Delubac, Anne Rios, Ralph Abi-Hachem1, David Jang, Bradley J. Goldstein, Carolyn Glass, Nicholas S. Heaton, David Hsu, Hans Clevers, Xiling Shen.

This work was supported by funding from the National Institutes of Health (R35GM122465, U01CA217514, U01CA214300) and the Duke Woo Center for Big Data and Precision Health.

PRESS CONTACT

Stewart Han, shan@terasaki.org, +1 818-836-4393

Terasaki Institute for Biomedical Innovation

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The Terasaki Institute for Biomedical Innovation (terasaki.org) is a non-profit research organization that invents and fosters practical solutions that restore or enhance the health of individuals. Research at the Terasaki Institute leverages scientific advancements that enable an understanding of what makes each person unique, from the macroscale of human tissues down to the microscale of genes, to create technological solutions for some of the most pressing medical problems of our time. We use innovative technology platforms to study human disease on the level of individual patients by incorporating advanced computational and tissue-engineering methods. Findings yielded by these studies are translated by our research teams into tailored diagnostic and therapeutic approaches encompassing personalized materials, cells and implants with unique potential and broad applicability to a variety of diseases, disorders, and injuries.

The Institute is made possible through an endowment from the late Dr. Paul I Terasaki, a pioneer in the field of organ transplant technology.

Stem Cell Reports

Experimental study

Not applicable

Rapid Tissue Prototyping with MicroOrganospheres

18-Aug-2022

Drs. Hans Clevers, David Hsu, and Xiling Shen are co-founders of Xilis, Inc, which aims to commercialize the MOS technology for clinical precision oncology. Dr. Clevers has been a member of Roches Corporate Executive Committee since March 18, 2022. His full disclosure is given at https://www.uu.nl/staff/JCClevers/. Drs. Zhaohui Wang and Shengli Ding recently took a leave from Duke to join Xilis.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Next generation patient avatars: Expanding the possibilities with MicroOrganospheres - EurekAlert

The Warren Alpert Foundation funding becomes the most significant award to support genetic counseling education nationwide

PHILADELPHIA Penn Medicine has been awarded a $9.5 million grant from the Warren Alpert Foundation to continue its efforts to increase diversity in genetic counseling, a field that, despite impressive leaps forward in genetic knowledge, lacks a diverse workforce. The Alliance to Increase Diversity in Genetic Counseling grant will support 40 underrepresented students in five genetic counseling programs in the Northeastern U.S. over five years to expand all dimensions of diversity. PI Kathleen Valverde, PhD, LCGC, the Director of the Master of Science in Genetic Counseling Program at the Perelman School of Medicine at the University of Pennsylvania, will lead this effort, joined by a consortium of participating Genetic Counseling masters programs from Boston University, Rutgers University, Sarah Lawrence College, and the University of Maryland School of Medicine. Ten students will be selected yearly, two from each program, to receive full tuition support and a cost of living stipend. Click here for more information on the Alliance to Increase Diversity Scholarships at the University of Pennsylvania.

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Masters Program in Genetic Counseling - Perelman School of Medicine at ...

Join dozens ofStanford Medicine studentswho receive up to three years of funding and valuable leadership skills asKnight-Hennessy Scholars(KHS).

KHS admits up to 100 select applicants each year from across Stanfords seven graduate schools, and delivers engaging experiences that prepare them to be visionary, courageous, and collaborative leaders ready to address complex global challenges. As a scholar, you join a multidisciplinary and multicultural cohort, participate in up to three years of leadership programming, and receive full funding for up to three years of your graduate studies at Stanford.

Candidates of any country may apply. KHS applicants must have earned their first undergraduate degree within the last seven years, and must apply to both a Stanford graduate program and to KHS.

If you aspire to be a leader in your field, we invite you to apply. The KHS application deadline is October 12, 2022. Learn more aboutKHS admission.

Knight-Hennessy Scholars application deadline: 1:00pm pacific time, October 12, 2022

MS Human Genetics and Genetic Counseling application deadline: December 6, 2022

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Admissions | Master's Program in Human Genetics & Genetic Counseling ...

Failed efforts do not overshadow fields progress, resolve.

The recent news of Biogen and Ionis Pharmaceuticals ending a clinical trial for their amyotrophic lateral sclerosis drug candidate and Roches failed Phase III study in Huntingtons disease (HD) are hard to bear for many families holding on to hope in the face of devastating diseases with limited options. Their drug development journeys underscore the highly challenging nature of tackling rare diseases. As a geneticist, Ive seen firsthand the difficulties these patients endure. But even in the face of what might seem like failure, there is great progress. New thinking, research, and discoveries are only made possible by those who bravely forge new paths to gain a better understanding of the human body, even when that risk entails failure. Success will come.

The silver lining? Our strategy is sound. There is no doubt that genetic medicines work at addressing root causality in monogenic rare diseases like HD.

Back in the mid-1980s, a group of scientists came together at Alta Ski Resort to investigate whether it was possible to detect increased mutations in the survivors of the Hiroshima and Nagasaki bombings. The conclusion was that current methods were insufficient, yet the meeting spurred an energized response around genetic sequencing that resulted in the federal government funding the multibillion-dollar, multinational, and multiyear project to sequence all six billion letters of the diploid human genome, which resulted in the publication of the draft sequence of the human genome in 2001, years earlier than expected.

In less than four decades since, we have unraveled the blueprint of human life, cataloged the vast majority of mutations in the genetic code, implemented global infrastructure to provide rapid and inexpensive genetic testing to patients and physicians, and have a first wave of genetic medicines saving human lives. This is breathtaking progress.

However, there is still much work to do, with numerous challenges centered on improving the delivery, selectivity, and tolerability of these genetic medicines. We know the medicines work; it is just a matter of getting the therapy to the tissue where the disease manifests, dialing in the selectivity for the gene of interest, and engineering out toxicities.

With HD, patients receive an injection into the spinal cord, but in order for enough of a relatively large genetic medicine to penetrate into the deep brain structures to be effective, the high concentrations of the drug injected at the surface of the brain may result in neurotoxicity.

Rapid advancements in the areas of delivery, selectivity, and tolerability are happening. For delivery, innovations are allowing us to deliver genetic medicines across the blood-brain barrier to allow uniform exposures across all brain regions and not setting up toxic gradientswhich has been difficult for large molecules. This method avoids the brain surface toxicity. Since HD is a disease that involves the whole body, delivering a solution systemically via the bloodstream may address the whole-body manifestations of the disease. These new delivery devices are also noninvasive, using either ultrasound or emerging tech, and allow effective administration in a previously impossible manner.

For selectivity, emerging technologies can identify and engage with only the targeted mutated gene. Weve essentially reverse engineered nature so that the genetic-medicine-to-gene-target interface wont tolerate any mismatches. The treatment is viewed by the body as a complementary sequence to the mutant gene, yet one that contains a biologically inert chemistry that ensures no off-target engagement. The end result will be clean, highly effective, and well-tolerated medicines.

Because many of these therapies are delivered systemically, they can trigger an immune reaction that renders the medicine intolerable, yet even on this front, we are seeing advancements. By using the bodys own intelligent design, scientists have copied the existing framework and then improved upon it using synthetic strategies that allow for greater tolerance, thereby preventing the normally useful immune response from derailing healing.

We are in the most exciting time in the history of medicine, bar none. The science is dazzling. Patients should feel very optimistic. Cures are coming not in decades, but in a matter of years. The innovation thats happening today will be the breakthrough therapies of tomorrow. If you are looking for a silver lining, here it is.

Dietrich Stephan, CEO, Chairman, and Founder, NeuBase Therapeutics

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The Silver Lining Of Innovation in Genetic Medicine - Pharmaceutical Executive

Asher Gerlach, age 6, is a special kid. Not only because hes one of just 2030 children in the world with an exceptionally rare genetic disease, according to medical literature, but also because he has a refreshing take on life.

Asher is super-affectionate. He snuggles with everyone, says his mom, Jen Gerlach. He cant say snuggle, so he says guggle instead. And please comes out as leese. So when he wants a hug, he says, Guggle leese? And hes hilarious. Hes always making us laugh.

Asher lives with his mom and two siblings, Isaac, age 8, and Shiloh, age 3, in San Jose, California. They enjoy being outdoors, swimming, and riding bikes together. One of their favorite family activities is building Brio trains and setting up train tracks, which often travel down the stairs and all around the houseinspired by their beloved late father, Josh, a structural engineer.

Jen is the most wonderful mother and advocate for Asher. Shes extremely well educated about his genetic condition, and shes motivated to learn as much as possible so she can help Asher and teach others, says Jenny Kim, MS, LCGC, a genetic counselor at Stanford Medicine Childrens Health.

Ashers genetic condition is Yuan-Harel-Lupski (YUHAL) syndrome. Its associated with neurological symptoms, physical differences, and developmental delays.

Its a rarely seen chromosome abnormality, which involves the short arm of chromosome #17. Its a duplication of this region that includes a couple of important genes, says Melanie Manning, MD, a medical geneticist.

Making the hard decision to proceed with genetic testing for Asher

At first, Gerlach balked at the idea of genetic testing for Asher. As a high school science teacher, she helped with the Human Genome Project, and she doubted the ability to accurately pinpoint errant genes. Yet after receiving the recommendation from different caregivers, she acquiesced. Shes extremely glad that she did.

Its terrifying for parents to take that hard step with genetic testing, but it gave me so much. It gave me the ability to talk intelligently about what is happening with my child, Gerlach says. And it gave me access to services. Before, I fought tooth and nail for services. Today, Im empowered to help Asher, and I have the tools I need to take care of him.

Stanford Medicine Childrens Health Genetics Services include consultation with geneticists and genetic counselors. They specialize in providing and coordinating comprehensive care for children and adults with suspected or confirmed genetic conditions.

Genetics has been my go-to contact. There have been many times on my journey where I knew that I needed help with a particular issue that Asher and I were facing, but I didnt know which specialty to talk to about the issue, Gerlach says. The genetics team is so informed and incredibly helpful with problem-solving.

To diagnose Ashers genetic condition, the team ran a chromosomal microarray, which can detect extra or missing pieces of genetic information. Genetic information contained on the chromosomes is in a delicate balance, and any extra or missing information may cause differences in health, development, and growth.

Knowing their childs genetic makeup is helpful for families. It helps them understand what to expect for the future, Dr. Manning says.

When families read the report of genetic findings for the first time, they can feel overwhelmed. The genetics team breaks it down in terms that are easy to digest and highlights whats important.

Finding out that he had YUHAL syndrome was horribly hard but empowering, Gerlach says. As a scientist, I joke that if you are going to have something, it might as well be cool and super-rare, but as a parent its terrifying.

The genetics team created a personalized care plan for Asher for the coming years. They also stay on top of new, relevant information related to his genetic condition.

Having genetic testing opens up options for families, Kim says. For Ashers family, we set them up with specialists, connected them with other families of kids with rare genetic disorders, and helped them get involved in YUHAL syndrome research.

Asher qualifies for special education because of his multiple disabilities. Despite his challenges, hes a high achiever without any behavioral problems.

Hes the only full-inclusion special needs child in his kindergarten class, which means he participates in all subjects with the help of a one-on-one aide, Gerlach says.

She describes Asher as a contented child who loves to laugh and goof around. The other day when she asked what he wanted for dinner, he said, First Ill eat chocolate, then a cupcake, and then noodles! Special treat first, Mama!

Genetics as a gateway to personalized, multidisciplinary care

Genetics partners with a wide range of specialties and subspecialties at Stanford Medicine Childrens Health to provide personalized, multidisciplinary care for Asher. Theres power in having all providers on the same page, especially for kids with highly complex medical and developmental needs.

Because we are so connected throughout the world, and we have world leaders in different conditions, we are able to provide care for children with these extremely rare disorders, says Miguel Moreno, MD, Ashers neurologist. Other childrens hospitals across the nation often refer children with rare diseases to us.

Asher receives care from 16 specialty programs at Stanford Medicine Childrens Health: general pediatrics; genetics; ear, nose, and throat; neurology; neuromuscular; pulmonology; cardiology; nephrology; urology; ophthalmology; plastic surgery; developmental-behavioral; audiology; orthopedics; physical therapy; and occupational therapy.

Recently, Asher was having obstructive airway issues and difficulty breathing. He needed to be evaluated under anesthesia by an ear, nose, and throat (ENT) specialist to find out why.

This was one of eight procedures that he needed, so I asked if there was any way they could do everything at once during his ENT surgery, and they did it. They coordinated it all, Gerlach says.

Douglas Sidell, MD, FACS, took charge in coordinating the day, which included a sleep-state endoscopy, laryngoscopy, tonsillectomy, sedated echocardiogram, blood draw, and more.

This level of coordination is really quite common. We try to do everything at once for all children, but this becomes particularly important in children with multiple complex needs. It saved Asher additional anesthesia, and it saved Jen from having to run back and forth to eight separate appointments and time away from work, Dr. Sidell says. It reflects on the exceptional communication we have among providers, which is part of our culture.

Getting neurological care for hypotonia and developmental delays

A main player on Ashers extensive care team is neurology. When Dr. Moreno first met Asher, he suspected a genetic disorder.

Ashers constellation of findingsfrom his extra digits, urinary issues, developmental delays, and autism featuresall pointed to a possible genetic condition, he says.

Earlier on, Gerlach worried that Asher might have seizures, so Dr. Moreno ran tests, including an EEG brainwave, which can detect abnormal activity associated with seizures. Ashers testing did not reveal seizure activity, and he did not have signs of cerebral palsy, but he was diagnosed with hypotonia (low muscle tone).

We are watching Ashers hypotonia, and we are providing extra support as he needs it, such as bracing and special orthotics so he can have confidence with walking, Dr. Moreno says. We are also keeping an eye out for peripheral nerve damage, but hes currently doing pretty well. He has good strength, and he isnt experiencing tremors or shaking.

Asher receives regular care at the Pediatric Neuromuscular Diseases Clinic, led by John Day, MD, PhD, which combines innovative research with individualized care for children with neuromuscular diseases. Hes also receiving physical therapy, occupational therapy, and speech-language therapy on a regular basis.

Asher is full of energy, and he has a great personality. Hes very feisty, Dr. Moreno says.

The right place to care for children with multiple needs

Gerlach chose Stanford Medicine Childrens Health because, she says, it is a mecca for everything. She appreciates how Ashers many doctors and caregivers work together so intricately and how the hospital specializes in rare diseases. She says she has not had a bad experience at Stanford Medicine Childrens Health, despite coming here hundreds of times.

The care has been stellar, so why would I go anywhere else? They treat Asher like a human, not a specimen, despite his super-rare disorder, Gerlach says. I always feel affirmed as a parent.

Its a two-way street caring for children with extremely rare genetic disorders. Parents, like Gerlach, play a role in moving knowledge forward.

Its been incredibly valuable to learn from Jen, especially about this extremely rare disease, says Natalie Dykzeul, MS, LCGC, a Stanford Medicine Childrens Health genetic counselor also working with the Gerlachs. You can tell that she and Asher have a special, unique bond.

Gerlach soaks in every moment with Asher, appreciating him as the complex, beautiful child that he is, all while watching him for signs of health problems. Its simply the journey that we are on, she concludes.

Learn more about Genetics Services at Stanford Medicine Childrens Health >

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Genetics Team Serves as Go-to for Mom of Son With Extremely Rare Disorder - Stanford Medicine Children's Health Blog - Stanford Children's Health

Since the medicine's first approval in 2016, nearly 130,000 people in the U.S. have been treated with Taltz

INDIANAPOLIS, Aug. 8, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today the availability of a new, citrate-free formulation of Taltz (ixekizumab) injection 80 mg/mL. The new formulation, which was recently approved by The U.S. Food and Drug Administration in May 2022, includes the same active ingredient as the original formulation. The new Taltz formulation significantly reduced injection site pain experienced by some people immediately following injection as shown by an 86% decrease in a visual analog scale (VAS) of pain versus the original formulation. Taltz is approved to treat adults and children six years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, adults with active psoriatic arthritis, active ankylosing spondylitis (AS) and active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

"Taltz has long delivered effective treatment with a well-established safety profile that addresses symptoms for people living with plaque psoriasis, psoriatic arthritis, AS and nr-axSpA," said Ashley Diaz-Granados, vice president, U.S. Immunology at Lilly. "We're proud of our investment in research that keeps the patient experience at the center. This new formulation provides yet another reason to choose Taltz, and we look forward to introducing it to patients who have not yet tried Taltz and providing a seamless transition for those already enjoying the medicine's benefits."

Taltz citrate-free demonstrated a safety profile consistent with the original formulation. The safety information for Taltz can be found below.

Existing Taltz patients will not need a new prescription, nor should they experience a gap in their therapy. The new formulation is currently being shipped across the U.S. with anticipated broad availability for both new and existing Taltz patients by the end of the month. In the interim, the original formulation of Taltz continues to be available until it is replaced by the citrate-free formulation. The citrate-free formulation of Taltz was approved by the European Medicines Agency in December 2021 with several markets launching now and many more anticipated in the coming months.

"Today is an exciting milestone for the nearly 30 million people around the world who live with the challenging symptoms of these autoimmune diseases that affect the skin and joints," said April Armstrong, M.D., MPH, professor of dermatology and associate dean of clinical research, Keck School of Medicine at the University of Southern California. "In my six years of prescribing Taltz, I've seen firsthand the significant impact Taltz has had for patients across multiple indications. The availability of Taltz as a citrate-free formulation represents an important advance in patient care that will allow more patients to experience less injection-site pain."

Lilly is committed to improving experiences for people treated with Taltz, providing the same active ingredient in a new citrate-free formulation. Lilly's investment into patient-centric research is evident as Taltz has been studied in more than 10,000 people in clinical trials globally and has been available in most markets for more than five years.1 In the U.S., more people living with psoriasis are treated with Taltz compared to any other IL-17A antagonist, adding to the nearly 130,000 people in the U.S. who have been treated with the medicine.2

To learn more about real success stories with Taltz, please visit Taltz.com.

IMPORTANT SAFETY INFORMATION FOR TALTZ

CONTRAINDICATIONSTaltz is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients.

WARNINGS AND PRECAUTIONSInfectionsTaltz may increase the risk of infection. In clinical trials of adult patients with plaque psoriasis, the Taltz group had a higher rate of infections than the placebo group (27% vs 23%). A similar increase in risk of infection was seen in placebo-controlled trials of adult patients with psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and pediatric patients with plaque psoriasis. Serious infections have occurred. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue Taltz until the infection resolves.

Pre-Treatment Evaluation for TuberculosisEvaluate patients for tuberculosis (TB) infection prior to initiating treatment with Taltz. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Taltz. Closely monitor patients receiving Taltz for signs and symptoms of active TB during and after treatment.

HypersensitivitySerious hypersensitivity reactions, including angioedema and urticaria (each 0.1%), occurred in the Taltz group in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post-marketing use with Taltz. If a serious hypersensitivity reaction occurs, discontinue Taltz immediately and initiate appropriate therapy.

Inflammatory Bowel DiseasePatients treated with Taltz may be at an increased risk of inflammatory bowel disease. In clinical trials, Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the Taltz group than the placebo group.During Taltz treatment, monitor patients for onset or exacerbations of inflammatory bowel disease and if IBD occurs, discontinue Taltz and initiate appropriate medical management.

ImmunizationsPrior to initiating therapy with Taltz, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with Taltz.

ADVERSE REACTIONSMost common adverse reactions (1%) associated with Taltz treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections. Overall, the safety profiles observed in adult patients with psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and pediatric patients with plaque psoriasis were consistent with the safety profile in adult patients with plaque psoriasis, with the exception of influenza and conjunctivitis in psoriatic arthritis and conjunctivitis, influenza, and urticaria in pediatric psoriasis.

Please see fullPrescribing InformationandMedication Guidefor Taltz. SeeInstructions for Useincluded with the device.

IX HCP ISI 07MAY2020

About TaltzTaltz(ixekizumab) is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor.IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Taltz inhibits the release of pro-inflammatory cytokines and chemokines.

About the Citrate-Free Injection Pain StudyThe citrate-free injection pain study (N=70) was a subject-blind, randomized, crossover study in healthy participants ages 18-75 years to determine injection site pain differences between Taltz citrate-free formulation compared to the original formulation of Taltz. The primary endpoint, pain intensity on injection, was measured by the Visual Analog Scale (VAS) of pain 0-100mm.3

About LillyLilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 47million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visitLilly.comandLilly.com/newsroomor follow us onFacebook, Instagram, Twitterand LinkedIn.

P-LLY

Cautionary Statement Regarding Forward-Looking StatementsThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Taltz as a treatment for people with moderate to severe plaque psoriasis, active psoriatic arthritis, active ankylosing spondylitis and active non-radiographic axial spondyloarthritis and other conditions and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study results to date. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

PP-IX-US-5653 08/2022 Lilly USA, LLC 2022. All rights reserved.

Taltz is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

SOURCE Eli Lilly and Company

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Lilly's Taltz (ixekizumab) Now Available in New, Citrate-Free Formulation to Reduce Injection Site Pain for Improved Patient Experience - PR Newswire

A new study on Alzheimer's disease ties the brain's immune response to the condition, while scientists have identified a better antibody treatment for cancer and possible cell toxicity in CRISPR-Cas9 gene editing.

For that and more, continue reading.

New Insights into Predisposition for Alzheimer's Disease

Researchers withThe Mount Sinai Hospital/Mount Sinai School of Medicine, working with fresh human brain tissue harvested by way of biopsies or autopsies from 150 donors,identified21 genes that could elevate the risk Alzheimer's disease.

In particular, they point to SPI1, a possible key regulator of microglia, immune cells in the brain. Microglia are primarily responsible for the brain's immune response but play an important role in the development and maintenance of neurons.

This is not the first study to target microglia as playing a vital role in the genetic risk and development of Alzheimer's disease because of their involvement in maintaining brain cells and battling inflammation, both issues with Alzheimer's disease. The research waspublishedinNature Genetics.

"Our study is the largest human fresh-tissue microglia analysis to date of genetic risk factors that might predispose someone to Alzheimer's disease," senior author Panos Roussos, M.D., Ph.D., professor of psychiatry and genetic and genomic sciences at the Icahn School of Medicine at Mount Sinai and director of the Center for Disease Neurogenomics, said.

"By better understanding the molecular and genetic mechanisms involved in microglia function, we're in a much better position to unravel the regulatory landscape that controls that function and contributes to AD," Roussos added. That knowledge, he said, could pave the way for novel therapeutic interventions for AD.

Microglia are notoriously difficult to isolate and examine, but they managed to cull 150 high-quality microglia. They then compared epigenetic, gene expression, and genetic information from the samples in both Alzheimer's and healthy aged patients. In addition to expanding on previous DNA regulatory sequence data and genes whose dysregulation directly contributes to Alzheimer's, they described the cell-wide regulatory mechanisms that may help identify genetic regions implicated in specific aspects of microglial activity.

A New, Broader, Cheaper and Faster Checkpoint Inhibitor

Scientists atTel Aviv Universityand theUniversity of Lisbonhaveidentifiedand synthesized a small molecule they believe can be a better antibody to treat a variety of cancers. As is well known, T cells express a protein called PD-1 that disables their activity when it binds to the PD-L1 protein expressed in cancer cells, essentially allowing cancer cells to shut down the immune response against them.

This led to the development of checkpoint inhibitors, antibodies that block either PD-1 or PD-L1, allowing the T cells to attack the cancer cells. However, these antibodies are expensive and have been difficult to develop for solid tumors they're quite effective in blood cancers. Using bioinformatic and data analysis tools, the researchers identified a smaller molecule that appears to control tumor growth and the other antibodies by inhibiting PD-1/PD-L1 binding. It is biological rather than synthetic and is much simpler and inexpensive to create. They also think it should be able to be taken orally instead of intravenously.

What are Cell Antennae?

Almost every cell type in the human body has a rod-like projection called cilia. Researchers fromOhio State Universitylookedat cilia on neurons in the brain in a mouse model of a neurological disorder called Bardet-Biedl syndrome.

They were looking at dopamine receptor 1, one of five proteins that regulate dopamine signaling. In some parts of the brain, this receptor switches on motivated behavior. But their research found that if the receptor gets stuck on cilia or isn't given an opportunity to localize to the cilia, messages telling the body to move are decreased.

Dopamine receptor 1 appears to require getting to and from neuronal cilia for proper signaling. Bardet-Biedl syndrome is in a class of diseases called ciliopathies, where dysfunctional cilia on a range of cell types can cause multiple organ system defects, blindness, obesity and intellectual disabilities. In the mouse model, deletion of these Bardet-Biedl syndrome proteins hindered the movement of certain receptors to and from primary cilia.

CRISPR-Cas9 Gene Editing can Cause Cell Toxicity and Genome Instability

Researchers atIRB Barcelonahavereportedthat if gene editing occurs at certain spots of the human genome, it can cause cell toxicity and genomic instability.

CRISPR-Cas9 is a type of very precise gene editing, and since the beginning, there have been concerns over off-target edits. The effect is mediated by the linchpin tumor suppressor protein p53 and depends upon the DNA sequence near the editing point and various epigenetic factors in the surrounding location. The researchers analyzed the most popular CRISPR library designed for human cells and identified 3,300 targeted spots demonstrating strong toxic effects. They also reported that about 15% of human genes contain at least one toxic editing point.

Future-Proof COVID-19 Treatments?

A study by theUniversity of Kentin the U.K. andGoethe-Universityin Germany have found new therapies for COVID-19 that may offer better protection against future variants and outbreaks.

They tested the sensitivity of various SARS-CoV-2 Omicron and Delta viruses to combinations of four approved antiviral drugs with betaferon, another class of antiviral drug naturally produced in the body. They found that these new combinations were, at least in cell culture assays, highly effective. The addition of the interferon with molnupiravir (Merck's Lagevrio), nirmatrelvir (one of the antivirals in Pfizer's Paxlovid) and aprotinin (Bayer's Trasylol) was much more effective than interferon combinations with remdesivir (Gilead's Veklury).

"These are exciting findings that will hopefully help to improve the treatment of vulnerable COVID-19 patients and to avoid the formation of resistant viruses as much as possible," Martin Michaelis, Ph.D., the University of Kent, stated.

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Research Roundup: 21 Genes Linked to Increased Risk of Alzheimer's and More - BioSpace