Category Archives: Gene Medicine

In part 2 of this video, Vladimir Maletic, MD, MS, clinical professor of neuropsychiatry and behavioral science, University of South Carolina School of Medicine, Greenville, interviews Bernadette DeMuri-Maletic, MD, medical director of Associated Mental Health Consultants and the TMS center of Wisconsin, Milwaukee, about the impact of loneliness on general health, including disease development such as depression or Alzhiemer, and the brain-body impact of marital connections. The pair recently co-presented a session titled "Love and Loneliness in the Time of COVID-19: Clinical Relevance of Relationships" at Psych Congress 2021 in San Antonio, Texas.

In the previous part 1, Dr Maletic, who is also Psych Congress Networks attention-deficit/hyperactivity disorder (ADHD) Section Editor, and Dr DeMuri-Maletic, explore the effects of social relationships, including loneliness and isolation, on the brain and the body.

In the upcoming part 3, they discuss the role relationships play in prevention psychiatry and the impact dyadic relationships have on the treatment of major depressive disorder.

Read the transcript:

Dr Vladimir Maletic: It appears that disruption of social relationships reverberates as a threat danger signal in the brain and that it causes changes in endocrine regulation, immune regulation, autonomic regulation.

One would suppose that it might have some impact on general health. I know you have recently reviewed the literature on the impact of loneliness on general health. What can you tell us about it?

Dr Bernadette DeMuri-Maletic: Vlad, there certainly is an impact both on physical and mental health. We see it in all areas. We see it in endocrine dysfunction.

Believe it or not, we can see an impact of relationships on things as specific as artery width and artery thickness. For example, in one study, they looked at the quality of dyadic relationships in married couples. They rated their interactions as positive or negative. Then they looked at artery width.

What they found was that those individuals who had negative interactions had thicker artery walls. That's affiliated with risk for stroke. You could draw from that study that perhaps bad marital relationships could put someone at higher risk for stroke. Interestingly, the converse was true.

Vladimir: That's pretty scary.

Bernadette: It is scary. The converse was true, if individuals had good relationships, good marital connection, they got along, they had thinner diameters of the carotid artery.

Also, the cardiovascular system is impacted. There was a study that looked at women who had more social support and more social integration, so to speak. They found that those women were at lower risk for cardiovascular disease and for cerebrovascular disease as well.

Vladimir: One aspect of mental health is a little bit awkward to talk about. We're both psychiatrists. We see patients with a variety of mental health issues but especially mood disorders. Asking about their intimacy is not always easy. Is that an important question? Does the quality of physical relationship have anything to do with mental health outcomes and overall physical health?

Bernadette: That's a great question. I agree that oftentimes we forget to discuss that. We forget to go deeper into our relationship history to look at people's physical intimacy and their connection in that area.

There was one study that looked at younger women. They were all moms. They were between ages 20 and 50. They corrected for their general health and also for their perceived stress.

They measured their telomere length. They found that women who had more physical intimacy the week before the study had longer telomeres. We know that shortened telomeres are affiliated with oxidative stress, with aging, with general poor health.

You could draw conclusion from that perhaps that physical intimacy can lead to overall better health, longevity, and improved health function. Vlad, to your question, we often forget to ask about physical intimacy in older adults in particular. There's been a strong link with physical intimacy and cognition in the older adult population.

They looked at individuals who were 57 to 83. They gave them questionnaires about their physical contact with their partners. Then they gave them a cognitive assessment, the ACE III. There was a clear correlation with frequency of sexual intimacy and their scores. They had higher scores on their cognitive evaluations suggesting the maintenance of physical relationships later in life.

Vladimir: That is really interesting. You also quoted a study that looked at the relationship between physical intimacy and the risk for developing Alzheimer's. I'm sorry. It's not physical intimacy if my memory serves me. It is more, did one have a partner in different phases in one's life? Can you remind us what the finding of that study was?

Bernadette: That was a very interesting study where they looked at partner status at midlife and then later in life. They found that individuals who were partnered at midlife but lost a partner due to divorce, to breakup, to death of a partner, those individuals had twice the risk of developing Alzheimer's disease overall.

Individuals who were not partnered, who lived alone both at midlife and later in life, had three times the risk of Alzheimer disease. The most remarkable thing to me in that study was they also factored in for the APOE4 risk gene for Alzheimer's.

Vladimir: That's apolipoprotein E4, right? It's one of the major risk genes.

Bernadette: Absolutely.

Vladimir: What do relationships have to do with genetic risk for Alzheimer?

Bernadette: This speaks to epigenetics. Those individuals even who had the risk gene, if they were partnered both at midlife and later in life, they had a much lower chance of developing Alzheimer's almost to the point where it negated the impact of that risk gene.

It's very interesting epigenetic phenomena that shows us that being partnered can influence our risk for developing Alzheimer's later in life.

Vladimir: That is amazing. Can you tell us a little bit about health hazards associated with being alone and lonely? Sometimes loneliness is not a choice. What can we do to help these individuals who are lonely? First, what are some of the risks of being lonely? Then, what can be done about it?

Bernadette: We've seen from multiple studies that we discussed in our talk that loneliness can have an impact on mental health, certainly, individuals, say, for example, health workers in general during the pandemic, they were at higher risk of developing mental health issues, depression and anxiety, if they perceived themselves as experiencing loneliness.

We also saw that loneliness can lead to cognitive dysfunction as we discussed earlier and also has a risk in cardiovascular and cerebrovascular health. The first thing we need to be aware of is, how do we diagnose loneliness? People can be alone and not feel lonely. What kind of interventions can we have to address that?

I've been using the UCLA loneliness screener or questionnaire. That's the screener that's been used in a lot of our studies that we've quoted today. It's a threequestion screener. It's very simple to use. It's downloadable on the Internet. It's free to use and it's quite reliable.

Once we've identified someone with loneliness, then we need to figure out what we can do to address that and how do we treat it?

Vladimir: There are different levels of loneliness from what I understood from your presentation.

Bernadette: There are. People can just be atrisk. Those individuals, we can intervene early and prevent them from having some of the health effects. There are some individuals who are quite isolated, but they're not quite at severe risk.

Then we have the people who are very isolated. Those individuals, we can see oftentimes who have more significant mental health problems who are living alone, who never leave their home. They're at very high risk.

In terms of treatment, we generally talk about things like CBT, looking at individuals who have cognitive distortions about how they interact with others, maybe referring them to a cognitivebehavioral therapist or doing some cognitive work in our own practices to help them look and change those distorted cognitions can be one treatment for loneliness.

Another treatment for loneliness is simple social skills training. We can do that in terms of our own practice or send them out to an outside therapist. We can look at something called supported socialization where you pair an individual up with someone out in the community and encourage them to do social activities either individually or in larger groups.

Then there are group activities that we can look at. For instance, in individuals who are more severely mentally ill, individuals maybe in community mental health settings, there is the Clubhouse phenomena, the Clubhouse movement. You can go online to Clubhouse International and find a Clubhouse in your area.

These centers have a lot of socialization. They have activities. It's a way for people who have more severe mental illness to get increase in their socialization.

Otherwise, other group activities such as group exercise, group gardening, interest groups, we found that group exercise is beneficial even without the intensity of exercise. Studies that looked at intensity of exercise going down, there was still significant benefit from the group activity.

What I do in my own practice is I often recommend going out for a friend for a walk in the morning or going out with someone, a coworker at work, and making a commitment with someone to do group exercise.

Vladimir: What are you hearing from your patients? If there is a change in the level of their social interaction, does it have some bearing in how they're doing?

Bernadette: Yes, I think so. The studies bear that out and anecdotally, I've seen that with my patients. They get double benefit, especially with exercise. In terms of working out with someone, there's more adherence because they have someone else that they have to really be accountable to, and so, it's been quite successful actually.

Vladimir: Great answer. Thank you.

Vladimir Maletic, MD, MS, is a clinical professor of psychiatry and behavioral science at the University of South Carolina School of Medicine in Greenville, and a consulting associate in the Division of Child and Adolescent Psychiatry, Department of Psychiatry, at Duke University in Durham, North Carolina. Dr Maletic received his medical degree in 1981 and his masters degree in neurobiology in 1985, both from the University of Belgrade in Yugoslavia. He went on to complete a residency in psychiatry at the Medical College of Wisconsin in Milwaukee, followed by a residency in child and adolescent psychiatry at Duke University.

Bernadette DeMuri-Maletic, MD, received her medical degree from the Medical College of Wisconsin. She completed residencies in both Psychiatry and Neurology at the Medical College of Wisconsin Affiliated Hospitals. Dr DeMuri is the medical director of associated mental health consultants and The TMS center of Wisconsin, both located in Milwaukee. She is an assistant clinical professor at the Medical College of Wisconsin. Dr DeMuri has a special interest in the treatment of mood disorders including treatment-resistant depression.

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The Impact of Loneliness on Disease Development - Consultant360

Pseudomonas aeruginosa, an organism responsible for thousands of deaths.

University of South Australia scientists have made a surprising discovery in the origins of an antibiotic-resistant gene previously thought to have been confined to Adelaide.

The gene, first detected in Adelaide in 2006, is carried by the nasty bacterium Pseudomonas aeruginosa, an organism responsible for thousands of deaths among immunocompromised, surgical, and burns patients due to its resistance to last resort antibiotics.

This gene makes infections resistant to the most potent antibiotics used in medicine imipenem and meropenem. Antibiotic resistant P. aeruginosa is now listed by the World Health Organization as a critical priority pathogen, one of 12 families of bacteria that pose the greatest threat to human health.

Until now, it was believed that the Adelaide Imipenemase (AIM-1) gene was only found in the South Australian capital city after being detected in clinical samples and healthcare-associated wastewater.

But a group of scientists led by UniSA microbiologist Associate Professor Rietie Venter has shown evidence of it worldwide, pinpointing its source in a harmless environmental organism present in soil, groundwater, wastewater, and even in plants.

The findings have been published in the journal Microbial Genomics.

The discovery suggests that the gene has mobilized at some stage and jumped from a harmless organism to a nasty pathogen.

Its an opportunistic pathogen which is ubiquitous and very resilient, says Assoc Prof Venter.

The team used innovative ways to track and characterize antimicrobial resistance, making their discovery through wastewater analysis. Their research revealed the AIM-1 gene was prevalent at many sites throughout Adelaide and South Australia, including in every wastewater sample and river water, hinting at a wider spread of the gene than originally thought.

We then investigated the possibility of a global distribution of the AIM-1 gene. Through extensive nucleotide and protein data base searching, we discovered the gene was also present in Asia, North America, and Europe.

However, AIM-1 was predominantly found in harmless environmental organisms and has only made the jump to the pathogen P. aeruginosa in two other locations so far (Iran and Iraq).

Genes that are mobile jump around all the time, but the scenario described in this study is much rarer, says Assoc Prof Venter.

However, as microbes are a great source of antibiotics and very competitive, it is highly likely that many bacterial resistant genes evolve in unknown organisms before making their way to dangerous pathogens, especially P. aeruginosa, which shares a habitat with harmless environmental organisms.

Assoc Prof Venter says the AIM-1 gene requires carefully monitoring.

If we can better understand why genes jump from environmental into human pathogens, we might be able to prevent it from happening more often, she says.

Reference: Worldwide distribution and environmental origin of the Adelaide imipenemase (AIM-1), a potent carbapenemase in Pseudomonas aeruginosa by Anteneh Amsalu, Sylvia A. Sapula, Jonathan J. Whittall, Bradley J. Hart, Jan M. Bell, John Turnidge and Henrietta Venter, 17 December 2021, Microbial Genomics.DOI: 10.1099/mgen.0.000715

P. aeruginosa that are resistant to carbapenems the best available antibiotics used for treating multi-drug resistant bacteria poses a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters.

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Surprising Discovery Proves That Deadly Gene Has Jumped From a Harmless Organism to a Deadly Pathogen - SciTechDaily

The last few decades have seen a genomic revolution. Researchers like us have interrogated the genomes of millions of people and uncovered gene variants that increase risks of diseases such as breast cancer, kidney disease, diabetes and schizophrenia. These help us understand the causes of the conditions, identify people at risk and develop new drugs.

However, currently in genomic research there is a drastic lack of diversity. In our new perspective piece, published this week in Nature Medicine, we show that 86 per cent of genomics studies use data from people of European descent despite only making up 16 per cent of the worlds population. Although this is usually defined by genetic ancestry, it overlaps strongly with people who identify with the white ethnic group.

Despite repeated calls for more diversity over recent years, progress has been limited and the eurocentric bias has actually risen. The proportion of studies conducted in African populations have, painfully, dropped from three per cent in 2016 to 1.1 per cent now.

What does this mean in practice? Imagine that a doctor looks at your genetic information and finds out that you are at risk of getting heart disease, although currently you do not have any symptoms. With this knowledge, a medic could recommend strategies to prevent or delay the disease onset.

But whether this prediction is accurate largely depends on your background. A previous study showed that genetic risk predictions based on eurocentric data are 4.5 times more accurate in individuals of European than African ancestry, meaning that in most cases genetics cannot be used to identify people at risk of disease if they are black.

The lack of diversity has led to major missed scientific opportunities. For example, by including people of African descent in one study, researchers found that a gene called PCSK9 affects cholesterol, which has led to new drugs for heart disease that benefit everyone.

So how can we overcome this and ensure representative data and health equity?

It is first important to understand how we got here. The dominance of European and American scientists in genomic research is a consequence of structural advantages, some of which are related to historical and present-day exploitation. The lack of diversity among researchers is a crucial driver of bias in genetic studies.

We believe that we can and should address this issue now. Together with four other international researchers we looked back at our own experiences in running global genomic studies in underrepresented populations, in an attempt to understand the current barriers and find ways to overcome them. We think that these are the most important areas in our roadmap towards genomic equity:

This is certainly doable. The success of some diverse studies illustrate indigenous groups and those at institutions in low- and middle-income countries can scale up in resources and skills to enable high-quality genomics research. For example, PARKH (the Pakistan Alliance for genetic RisK factors for Health) is a study of 45,000 people from Pakistan to identify genetic causes of mental illness. Such research helps to highlight the contribution of heritable physiological causes and reduce the stigma of mental illness.

Genomic research has received billions of pounds in funding to improve the health of people. But it is now clear that some of the benefits will be exclusive to white people this must change.

We have to fundamentally alter the way we do research, including leading roles for diverse global researchers, genuine partnerships with the communities and strategic funding that is tied to capacity building. Only then can all benefit from the genomic revolution.

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Why the world's genomic revolution is incomplete - Telegraph.co.uk

Nucleome Therapeutics appoints Nigel Clark as Chief Business Officer

Nigel brings 20+ years of commercial and senior managerial experience in the biotech and pharma industry

Oxford, UK, 15 February 2022 Nucleome Therapeutics, a biotechnology company decoding the dark matter of the human genome to uncover novel ways to treat disease, today announces the appointment of Dr Nigel Clark as Chief Business Officer with immediate effect. Nigel has more than 20 years of deal-making experience from negotiating and executing over 20 major transactions worth over $1.6bn.

Most recently, Nigel served as Senior Vice President of Business Development at Kymab, which was acquired by Sanofi in 2021. In his role at Nucleome, Nigel will serve on the executive leadership team and will shape and oversee Nucleomes business and corporate development strategy.

Nigel has broad commercial experience, an impressive record of high value transactions and long-standing relationships across the life sciences industry. I am thrilled to welcome him to our executive team, commented Dr Danuta Jeziorska, Chief Executive Officer and Founder of Nucleome. He joins us at an incredibly exciting stage as we continue to decode the dark genome to uncover precision medicines and began biological validation of our first targets with the ambition to progress them to discovery programmes for the treatment of autoimmune diseases.

Dr Nigel Clark, Chief Business Officer of Nucleome, said: The opportunity to join Nucleome Therapeutics, a company with real potential to transform drug discovery and translational medicine, is truly exciting. I have been privileged in my career to date to work with the very best in the industry and I look forward to working with the exceptional executive and scientific team at Nucleome to realise a paradigm shift in the research and development of novel therapeutics to improve patient's lives.

Dr Nigel Clark most recently served as SVP Business Development and a member of the executive team at Kymab which was divested in 2021 to Sanofi for $1.1bn upfront and a further $300M of success-based milestones. Previous roles include Chief Business Officer at Syntaxin (divested to Ipsen Pharma), VP of Business Development at Vernalis and a member of the senior executive committee as well as President, Vernalis Canada. Nigel has also held leadership roles at Ribotargets and British Biotech and was co-head of the biotech business unit at Datamonitor. He was awarded a Ph.D. from the University of Reading for research conducted into HIV gene regulation and completed his scientific training as a post-doctoral scientist at the department of biochemistry, University of Oxford.

End

About Nucleome Therapeutics Nucleome Therapeutics is decoding the dark matter of the human genome to uncover novel ways to treat disease. The dark genome holds more than 90% of disease-linked genetic variants whose value remains untapped, representing a significant opportunity for drug discovery and development. We have the unique ability to link these variants to gene function and map disease pathways. Our cell type-specific platform creates high resolution 3D genome structure maps and enables variant functional validation at scale in primary cell types. This enables us to discover and develop novel, better and safer drugs. The initial focus of the company is on lymphocytes and related autoimmune disease. Our ambition is to build a robust pipeline of drug assets, with corresponding biomarkers. Nucleome Therapeutics was founded by leading experts in gene regulation from the University of Oxford and backed by investment from Oxford Sciences Innovation. For more information, please visit http://www.nucleome.com.

For more information, please contact:

Nucleome TherapeuticsDr Danuta Jeziorska, Chief Executive Officer & Foundercontact@nucleome.com

Consilium Strategic CommunicationsMary-Jane Elliott/ Sukaina Virji/ Lindsey NevilleNucleome@consilium-comms.com

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Nucleome Therapeutics appoints Nigel Clark as Chief Business Officer - GlobeNewswire

Cytiva and NecstGen say they plan to accelerate the development of new cell and gene therapies globally by entering into a strategic collaboration. Cytiva will provide its technologies, services, and solutions to NecstGen, and both organizations will share their knowledge and expertise as research programs are translated into next generation therapies, according to officials at both companies.

Cell and gene therapies are transformative medicines and accelerating their development requires harnessing the power of the industry, says Catarina Flyborg, vice president, cell and gene therapy, Cytiva. By sharing our expertise and providing NecstGen with access to our team of specialists, Cytiva will play a critical role in taking translational research from the laboratory to the bedside.

NecstGen is a non-profit contract development and manufacturing organization (CDMO) specializing in cell and gene therapies in the Netherlands. It brings the development, production, QC, QA, and QP functions together in a new 4,000 m2 facility in Leiden Bio Science Park, the largest bio-cluster in the Netherlands, notes Paul Bilars, CEO, NecstGen.

The new facility is designed to serve all organizations worldwide, particularly academic and small/large industry enterprises that are looking to bring their research to the clinical stage. NecstGen will provide process development, cGMP manufacturing services up to 200L, and cleanroom rental.

Our partnership with Cytiva will provide us with the flexible and scalable solutions needed by pioneers in the field of cell and gene therapy, says Bilars. Working together, we will accelerate the development of future therapies, bringing these to patients faster.

During the first half of 2021, there were 1,328 regenerative medicine trials underway globally sponsored by non-industry groups such as academic centers and government entities, according to the Alliance for Regenerative Medicine. Small and mid-size enterprises and academic centers play an important role in the development of novel cell and gene therapies.

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Cytiva and NecstGen Collaborate on Development of Cell and Gene Therapies - Genetic Engineering & Biotechnology News

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Cross-disciplinary team identifies genetic cause of rare, undiagnosed lung disease

New research from Washington University School of Medicine in St. Louis has solved the medical mystery of why a 2-year-old child seemingly healthy at birth succumbed to an undiagnosed, rare illness. On the left is normal lung tissue showing air sacs with thin cell layers for the exchange of oxygen and carbon dioxide. On the right is the patient's lung tissue. Because of a mutation in the RAB5B gene, the walls of the air sacs are thick and unable to participate in gas transfer.

New research from Washington University School of Medicine in St. Louis has solved the medical mystery of why a 2-year-old child seemingly healthy at birth succumbed to an undiagnosed, rare illness. The research team identified a previously unknown genetic cause of interstitial lung disease, providing answers to the parents and doctors puzzled by the childs condition.

The research, conducted as part of the National Institutes of Healths (NIH) Undiagnosed Diseases Network, demonstrates, among other benefits, how an interdisciplinary team of researchers can work together to solve medical mysteries, helping patients understand a diagnosis, prognosis and what a genetic abnormality may mean for family members and family planning.

The study is published the week of Jan. 31 in the Proceedings of the National Academy of Sciences. The Undiagnosed Diseases Network is a national research network aimed at diagnosing rare and previously undescribed diseases in patients whose conditions present as medical mysteries. Washington University serves as a clinical site that evaluates patients, and a model organism screening site that develops models to study genes in zebrafish and roundworms.

Interstitial lung disease is a broad term for a disease in which the lungs gradually deteriorate, causing scarring that makes it increasingly difficult to breathe. Several gene abnormalities have been associated with interstitial lung disease in infants and children, but some patients have the disease despite harboring none of the known genetic abnormalities. In the new study, the researchers were presented with the case of a young child with interstitial lung disease of unknown cause. The child later died of the disease.

The researchers analyzed the childs DNA code as well as the DNA code of both parents. A team of bioinformatics specialists at Baylor College of Medicine then narrowed down the initial long list of DNA code changes or genetic variants they identified many of which are harmless to a smaller list of possible culprits. The lung tissue from the child had evidence of a problem with surfactant in the lungs. In the lungs air sacs, surfactant is a complex mixture of proteins and lipids that reduces surface tension in the air sacs and keeps them open, easing the exchange of oxygen and carbon dioxide during breathing. Many people with interstitial lung disease have abnormalities in the surfactant protein genes. But this child did not have any genetic variants in the code of the surfactant protein genes.

Rather, the researchers found a variant in a gene that makes a protein called RAB5B that turns out to be part of the cellular machinery that processes the surfactant proteins, the researchers later learned. They showed that the RAB5B protein plays a vital role in packaging the surfactants into tiny compartments called vesicles and moving them to their proper locations. In this case, the genetic variant did not simply prevent the protein from working the genetic variant caused the protein to be actively harmful.

When mutations happen that break a protein, usually the protein just doesnt work anymore its function is missing, said co-senior author Tim Schedl, PhD, a professor of genetics. But this is a case where the broken protein is not only not working, its actively poisoning other processes. This results in the loss of the surfactants in the lungs.

The researchers were able to identify this abnormality by studying the genetic variant in roundworms that are called C. elegans. The child had only one abnormal copy of the gene, demonstrating that even having one normal copy did not compensate for the poisonous protein produced by the mutated copy. Worms with one abnormal copy required three normal copies to restore normal function, demonstrating the poisonous activity of the abnormal copy, according to experiments conducted by first author Huiyan Winnie Huang, PhD, an instructor in pediatrics. And consistent with these genetics, the researchers found that neither of the childs parents had the genetic abnormality, indicating that the variant was only present, by happenstance, in the childs genes and was therefore a new variant in the DNA that arose during embryonic development.

In so many cases, we dont know why a patient has a particular disease, said co-senior author Steven L. Brody, MD, the Dorothy R. and Hubert C. Moog Professor of Pulmonary Medicine. But we were able to solve this case, and theres a real satisfaction in that. Potentially, this could lead to finding answers for other people who have diseases similar to this.

Added co-author Jennifer A. Wambach, MD, an associate professor of pediatrics: This gene, RAB5B, is now associated with interstitial lung disease in children. There are patients with a clinical diagnosis of interstitial lung disease without a genetic explanation. For these patients, sequencing RAB5B may reveal changes in their DNA code that could account for their disease. Knowing the underlying genetic cause and identifying other patients with the same genetic problem can help us better predict the course of the disease, so we can better prepare patients and their families for what is to come, such as whether the patient may respond to treatments, or worsen to needing a lung transplant, or whether it may be appropriate to begin discussing compassionate care.

While the diagnosis was not able to help the patient in this case, knowledge of the underlying cause allowed the parents to know that the genetic variant was not inherited and there would be a very low chance of future children having the same disease.

Because these types of genetic diseases are so rare, theres very little information out there for patients or families, said co-senior author Stephen C. Pak, PhD, an associate professor of pediatrics. But collectively, there are millions of people who live with rare genetic diseases. Thats why the Undiagnosed Diseases Network was formed to bring together bioinformatics specialists, researchers, lung biologists, pediatricians and other experts into this type of unique collaboration to try and address this unmet need.

This work was supported by the National Institutes of Health (NIH) Common Fund, through the Office of Strategic Coordination/Office of the NIH Director, grant numbers U54 NS108251 and U01 HG007709. Funding also was provided by the NIH, grant number R01 GM100756; the NIH Office of Research Infrastructure Programs, grant number P40 OD010440; the National Heart, Lung, and Blood Institute (NHLBI) of the NIH through the LungMAP consortium, grant number U01HL122642, and the LungMAP Data Coordinating Center, grant number 1U01HL122638; the Childrens Discovery Institute; the St. Louis Childrens Hospital Foundation; and The Foundation for Barnes-Jewish Hospital.

Huang H, et al. A dominant negative variant of RAB5B disrupts maturation of surfactant protein B and surfactant protein C. Proceedings of the National Academy of Sciences. Jan. 31, 2022.

Washington University School of Medicines 1,700 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, and is among the top recipients of research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Researchers solve medical mystery of deadly illness in young child Washington University School of Medicine in St. Louis - Washington University...

DUBLIN, February 04, 2022--(BUSINESS WIRE)--The "Orthopedic Regenerative Medicine Market, by Treatment Type, by Disease Indication, by End User, and by Region - Size, Share, Outlook, and Opportunity Analysis, 2021 - 2028" report has been added to ResearchAndMarkets.com's offering.

Regenerative medicines can be consider as manufacturing of pharmaceuticals for the regrowth of cells, replacing damaged cells, organs, or tissues .The developing methods for medicines includes the generation, tissue engineering, and therapeutic stem cells and production of artificial organs.

Regenerative orthopedic medicines can help in healing damaged tissues, and improve the discomfort and pain which occurred due to musculoskeletal diseases. These regenerative medicines can be developed by using stem cells, plasma-rich sources, biological tissues, and bone marrow. Orthopedic regenerative medicines help in healing injuries of ligament, tendon, bone, spinal disc, muscle, cartilage, and musculoskeletal tissues.

Market players are indulged in receiving approvals from regulatory authorities for the treatment of orthopedic diseases, which is expected to drive the growth of the global orthopedic regenerative medicine market over the forecast period. For instance, on June 28, 2021, Curasan AG, a company which produce regenerative medicines, has received approval from U.S. Food and Drug Administration (FDA) and The National Health Surveillance Agency (ANVISA) Brazilian regulatory agency for CERASORB Foam for use with antibiotics which is a ?-TCP collagen matrix which use for delivering antimicrobials to wound surface to inhibit microbes capable of healing. The major use of this foam is minimizing the risk of reinfection of the infected area by combining it with antibiotics.

Increasing inorganic activities by market players such as collaborations, partnerships, and agreements is expected to drive the growth of the global orthopedic regenerative medicine market over the forecast period. For instance, on January 14, 2021, Bone Therapeutics, which is a manufacturer of cell therapy products, signed partnership with Rigener and, a company which develops and produces cGMP products, used for cell-gene therapy. The aim of this partnership was to develop products based on bone therapeutics by expanding research for therapeutic portfolio. This partnership will be focused on augmented bone forming cells that are programmed for specific task and by studying the new mechanisms of action for gene modifications for orthopedic regenerative medicines.

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Company Profiles

Ortho Regenerative Technologies Inc.

Personalized stem cells Inc.

Anika Therapeutics Inc.

Arthrex Inc.

Baxter International Inc.

Conmed Corporation

Aziyo Biologics

Curasan Inc.

Swiss biomed Orthopedics AG

Octane Medical Inc.

Stryker Corporation

Carmell Therapeutics Corporation

Zimmer Holdings

Smith & Nephew plc.

NuVasive Inc.

Key features of the study:

This report provides an in-depth analysis of the global orthopedic regenerative medicine market, provides market size (US$ Million), and compound annual growth rate (CAGR %) for the forecast period (2021-2028), considering 2020 as the base year.

It elucidates potential revenue opportunities across different segments and explains attractive investment proposition matrix for this market

This study also provides key insights about market drivers, restraints, opportunities, new product launches or approval, regional outlook, and competitive strategies adopted by the leading players

It profiles leading players in the global orthopedic regenerative medicine market based on the following parameters - company overview, financial performance, product portfolio, geographical presence, distribution strategies, key developments and strategies, and future plans

Insights from this report would allow marketers and the management authorities of the companies to make informed decision regarding their future product launch, technology up-gradation, market expansion, and marketing tactics

The global orthopedic regenerative medicine market report caters to various stakeholders in this industry including investors, suppliers, manufacturers, distributors, new entrants, and financial analysts

Stakeholders would have ease in decision-making through various strategy matrices used in analyzing the global orthopedic regenerative medicine market

Key Topics Covered:

1. Research Objectives and Assumptions

2. Market Overview

Report Description

Market Definition and Scope

Executive Summary

Market Snippet, By Treatment Type

Market Snippet, By Disease Indication

Market Snippet, By End User

Market Snippet, By Region

Coherent Opportunity Map (COM)

3. Market Dynamics, Regulations, and Trends Analysis

4. COVID - 19 Impact Analysis

5. Global Orthopedic Regenerative Medicine Market, By Treatment Type, 2017 - 2028 (US$ Million)

6. Global Orthopedic Regenerative Medicine Market, By Disease Indication , 2017 - 2028 (US$ Million)

7. Global Orthopedic Regenerative Medicine Market, By End User, 2017 - 2028 (US$ Million)

8. Global Orthopedic Regenerative Medicine Market, By Region, 2017 - 2028 (US$ Million)

9. Competitive Landscape

10. Section

For more information about this report visit https://www.researchandmarkets.com/r/c8xqzo

View source version on businesswire.com: https://www.businesswire.com/news/home/20220204005208/en/

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Global Orthopedic Regenerative Medicine Market to 2028 - Featuring Anika Therapeutics, Baxter International and Stryker Among Others -...

JERUSALEM, Feb. 3, 2022 /PRNewswire/ --The Hadassah Cancer Research Institute at the Hadassah University Medical Center in Jerusalem, announced today that using artificial intelligence (AI), researchers have developed, an algorithm to identify, with an unprecedented 96.5% level of accuracy, all possible deleterious mutations of TP53 gene which are commonly found in 50% of tumors. This breakthrough can potentially lead to improved genetic screening and consultation and to improved precision medicine for cancer patients.

This groundbreaking algorithm was trained using AI, huge cancer and normal genomics databases coupled with computational and experimental parameters specific to TP53 gene. Prof. Thierry Soussi (Sorbonne Universit, Paris, France), a world leading researcher of TP53 gene, lent his expertise to an international research collaboration, led by Dr. Shai Rosenberg, aimed at increasing identification of variants posing risk of developing cancer from variants that are not, from 190 (in the ClinVar database) to all 2,314 possible missense variants.

This gene-specific, AI approach can be generalized to other cancer genes and thus, contribute to more accurate genetic screening and consultation. Additionally, it can lead to more effective precision medicine for oncological patients by the creation of customized cancer treatment decision support systems that are able to identify and discern the important mutations that require treatment from the total number of somatic mutations of the tumor.

"The research and technology behind this breakthrough not only provide life-saving screening for carriers of previously unknown cancerous mutations who may be at increased risk, but it is also critical for genomic analysis of somatic mutation profiles in all tumors," said Prof. Michal Lotem, MD, Head of the Center for Melanoma and Cancer Immunotherapy, Dept. of Oncology.

"Hadassah Medical Center has been at the forefront of promoting technological innovation in medicine in order to provide patients in our care with the most advanced treatment options," said Prof. Aron Popovtzer a Professor of Radiation Oncology and Head of the Sharett Institute of Oncology. "Following this important milestone, Dr. Rosenberg's research group will continue actively working to develop similar models for additional cancer genes."

Read the full articleby Dr. Rosenberg, published in the prestigious - Briefings in Bioinformatics Journal. Dr. Rosenberg is a physician-researcher at Hadassah Medical Center. He is a senior Neuro-Oncologist and heads the Laboratory for Computational Biology of Cancer. He is a graduate of the Rothschild Excellence Program and the Technion's MD-PhD Program. He heads the Sagol program for dual degree in Medicine and Computer Science in the Faculty of Medicine in the Hebrew University.

This research is funded by Israel Academy of Sciences and Humanities, Trudy Mandel Louis Charitable Trust, Y.M.H and Hadassah-France. The research of Professor Soussi by Hadassha France.

For more information on the Hadassah Cancer Research Institute, contact:Amalia HerszkowiczHadassah Research Institute (HCRI)[emailprotected]

SOURCE Hadassah Cancer Research Institute

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Predictive-AI Algorithm Used to Successfully Identify Common Cancerous Gene Mutations Demonstrated at Hadassah Cancer Research Institute - PRNewswire

The CGTs gaining marketing authorisation in Europe and the US each year can currently be counted in single digitals, but hundreds of potential new CGTs are in the pipeline. According to the AMR report, 136 of the 956 unique therapies under development are already in the phase three stage of clinical trials commonly the last stage of clinical trials where the safety and effectiveness of the proposed new treatments is compared to existing treatments.

Much of the research ongoing is focused on delivering new cancer treatments, but CGTs have potential utility across other areas of medicine. The AMR report highlights the efforts being undertaken by medical researchers across industry, academia and government to develop new CGTs to address problems such as heart failure, rare genetic diseases, and neuromuscular diseases, for example.

Research overseen by the Massachusetts Institute of Technologys Center for Biomedical Innovation, published in 2018, projects that around 500,000 patients in the US will have been treated with between 40 and 60 approved CGTs by 2030.

CGTs are often developed to treat small patient populations at high cost. This poses a problem for budget-constrained health systems in terms of fitting the therapies within existing reimbursement models in a way which enables the developers of the therapies to obtain a fair return on their investment. A lack of harmonisation over the way each country approaches reimbursement creates uncertainty for researchers and their financial backers.

In addition, small biotech companies behind CGTs must navigate a complex regulatory framework and find infrastructure solutions to scale-up the manufacturing of approved treatments.

The challenges facing the CGT sector are well-recognised by policy makers, and efforts to resolve them are underway across Europe at EU level, EU27 member state level and within the UK alone to address them. We have set out examples of the initiatives we think could be taken forward.

Covid-19 has shown how collaborative, concerted efforts can drive innovation forward. There is an opportunity for stakeholders across the CGT sector to come together differently, perhaps in a pre-competitive way, to help drive economies that reduce costs.

The BioPharmaceutical industry has historically turned to industry-wide collaboration through organisations such as the Innovative Medicines Initiative (IMI) and the Pistoria Alliance to address resource-wasting replication of pre-competitive research activities and solve bottlenecks in drug discovery and development across diseases. CGT should be no exception.

An international group of senior researchers is lobbying the G7 to reform the way they manage collaboration on emerging technologies. The proposed framework would produce model, multilateral agreements on sharing and exploiting emerging technologies, including CGTs, that companies, universities and governments could follow; reducing uncertainty about IP, standardisation, data sharing, researcher mobility and other contentious issues.

Standardisation will cut development time and costs of CGTs too. Companies are already working with regulators and standard setting bodies, such as the International Organization for Standardisation, to agree regulatory standards. Various groups globally are discussing harmonisation of best practices to eliminate or reduce costs. In time, standardisation will facilitate technology platforms that are able to target many different diseases; viral-vector platforms that target a range of diseases in gene therapy are already in development.

Innovative payment models are already being used by health systems across Europe for CGTs to address affordability. As the pipeline of CGTs approaching market is increasing, there is a growing awareness and acknowledgment that outcomes-based reimbursement (OBR) schemes offer a potentially effective mechanism to reduce the long-term data uncertainty and have the potential to ensure greater access and reward for efficacious therapeutic innovation.

One of the takeaways from NICEs regenerative medicines study in 2016 is that outcomes-based payments increased the probability of a therapy being cost-effective but without the risk of eroding product value, unlike upfront discounts. When evaluating an OBR scheme it will be important to consider the feasibility of patient follow-up and the availability of a suitable data collection infrastructure, such as a patient registry. Covid-19 sped the adoption of digitally-enabled processes and CGT companies can leverage new practices such as remote monitoring for long-term patient follow-up. Clearly different CGTs may call for different pricing models in different markets.

The ability to combine clinical trial data and real world data is seen by many as one of the most critical transformations occurring in CGT development. Looking to strike a careful balance between the benefits of early access and the potential, still-unknown, long-term safety risks, regulators including the European Medicines Agency (EMA) and Medicines & Healthcare products Regulatory Agency (MHRA) in the UK are already performing accelerated assessment and granting approvals for CGTs on the condition that real-world evidence (RWE), based on real-world data, is periodically submitted thereafter.

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Cell and gene therapies: our eyes to the future - Pinsent Masons

Researchers have discovered a mechanism that may explain why people with COVID-19 lose their sense of smell.

Published online February 1 in the journal Cell, the new study finds that infection with the pandemic virus, SARS-CoV-2, indirectly dials down the action of olfactory receptors, proteins on the surfaces of nerve cells in the nose that detect the molecules associated with odors.

Led by researchers from NYU Grossman School of Medicine and Columbia University, the new study may also shed light on the effects of COVID-19 on other types of brain cells and other lingering neurological effects of COVID-19 such as brain fog, headaches, and depression.

Experiments showed that the presence of the virus near nerve cells (neurons) in olfactory tissue brought an inrushing of immune cells, microglia, and T cells that sense and counter infection. Such cells release proteins called cytokines that changed the genetic activity of olfactory nerve cells, even though the virus cannot infect them, say the study authors. Where immune cell activity would dissipate quickly in other scenarios, in the brain, according to the teams theory, immune signaling persists in a way that reduces the activity of genes needed for the building of olfactory receptors.

Our findings provide the first mechanistic explanation of smell loss in COVID-19 and how this may underlie long COVID-19 biology, says co-corresponding author Benjamin tenOever, PhD, professor in the Departments of Medicine and Microbiology at NYU Langone Health. The work, in addition to another study from the tenOever group, also suggests how the pandemic virus, which infects less than 1 percent of cells in the human body, can cause such severe damage in so many organs.

One unique symptom of COVID-19 infection is loss of smell without the stuffy nose seen with other infections like the common cold, researchers say. In most cases, the smell loss lasts only a few weeks, but for more than 12 percent of people with COVID-19, olfactory dysfunction persists in the form of ongoing reduction in the ability to smell (hyposmia) or changes in how a person perceives the same smell (parosmia).

To gain insight into COVID-19induced smell loss, the current authors explored the molecular consequences of SARS-CoV-2 infection in golden hamsters and in olfactory tissue taken from 23 human autopsies. Hamsters represent a good model, being mammals that both depend more on the sense of smell than humans, and that are more susceptible to nasal cavity infection.

The study results build on the discovery over many years that the process that turns on genes involves complex 3D relationships, where DNA sections become more or less accessible to the cells gene-reading machinery based on key signals, and where some DNA chains loop around to form long-range interactions that enable the stable reading of genes. Some genes operate in chromatin compartmentsprotein complexes that house the genesthat are open and active, while others are compacted and closed, as part of the nuclear architecture.

In the current study, experiments confirmed that SARS-CoV-2 infection, and the immune reaction to it, decreases the ability of DNA chains in chromosomes that influence the formation of olfactory receptor building to be open and active, and to loop around to activate gene expression. In both hamster and human olfactory neuronal tissue, the research team detected persistent and widespread downregulation of olfactory receptor building. Other work posted by these authors suggests that olfactory neurons are wired into sensitive brain regions, and that ongoing immune cell reactions in the nasal cavity could influence emotions, and the ability to think clearly (cognition), consistent with long COVID.

Experiments in hamsters recorded over time revealed that downregulation of olfactory neuron receptors persisted after short-term changes that might affect the sense of smell had naturally recovered. The authors say this suggests that COVID-19 causes longer-lasting disruption in chromosomal regulation of gene expression, representing a form of nuclear memory that could prevent the restoration of olfactory receptor transcription even after SARS-CoV-2 is cleared.

The realization that the sense of smell relies on fragile genomic interactions between chromosomes has important implications, says Dr. tenOever. If olfactory gene expression ceases every time the immune system responds in certain ways that disrupts inter-chromosomal contacts, then the lost sense of smell may act as the canary in the coal mine, providing early signals that the COVID-19 virus is damaging brain tissue before other symptoms present, and suggesting new ways to treat it.

In a next step, the team is presently seeing whether treating hamsters with long COVID with steroids can restore restrain damaging immune reactions (inflammation) to protect nuclear architecture.

Along with Dr. tenOever, authors of the current study from the Department of Microbiology at NYU Langone Health were Justin Frere, Rasmus Moeller, Skyler Uhl, and Daisy Hoagland. Also leading the study were corresponding authors Jonathan Overdevest and Stavros Lomvardas from the Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University. Additional contributors included Marianna Zazhytska, Albana Kodra, Hani Shayya, Stuart Firestein, Peter Canoll, and James Goldman. Also making important contributions were study authors John Fullard and Panos Roussos of the Icahn School of Medicine at Mt. Sinai; Arina Omer of Baylor Genetics in Houston; and Qizhi Gong of the Department of Cell Biology and Human Anatomy, School of Medicine, University of California at Davis.

Funding for the study was provided by National Institutes of Health grants NIDCD 3R01DC018744-01S1 and U01DA052783, as well as a Howard Hughes Medical Institute Faculty Scholars award and the Zegar Family Foundation.

Greg WilliamsPhone: 212-404-3500gregory.williams@nyulangone.org

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Mechanism Revealed Behind Loss of Smell with COVID-19 - NYU Langone Health