The Future of Fertility – The New Yorker

In 2016, two Japanese reproductive biologists, Katsuhiko Hayashi and Mitinori Saitou, made an announcement in the journal Nature that read like a science-fiction novel. The researchers had taken skin cells from the tip of a mouses tail, reprogrammed them into stem cells, and then turned those stem cells into egg cells. The eggs, once fertilized, were transferred to the uteruses of female mice, who gave birth to ten pups; some of the pups went on to have babies of their own. Gametes are the cells, such as eggs and sperm, that are essential for sexual reproduction. With their experiment, Hayashi and Saitou provided the first proof that whats known as in-vitro gametogenesis, or I.V.G.the production of gametes outside the body, beginning with nonreproductive cellswas possible in mammals. The mice that had descended from the lab-made egg cells were described as grossly normal.

The Japanese experiment may change the science of human reproduction. The first successful in-vitro fertilization, in 1978, made it possible to conceive an embryo outside the body. Today, approximately two per cent of all babies in the United States are conceived in a lab, through I.V.F.last year, analysts valued the global I.V.F. market at more than twenty-three billion dollars. Egg cells have become commodities that are harvested, bought, donated, and preserved. But egg cells, some of the most complex cells in the body, and large enough to be visible to the naked eye, are difficult to obtain; as a woman ages, their number and quality decline. If ripe human eggs could be derived from a persons skin cells, it would avoid most of the cost, almost all of the discomfort, and all of the risk of IVF, the Stanford bioethicist Henry Greely wrote in his 2016 book, The End of Sex and the Future of Human Reproduction, addressing new techniques to make stem cells which had won the Nobel Prize in 2012. He predicted that in the next twenty to forty years sex will no longer be the method by which most people make babies (among humans with good health coverage, he qualified).

A hundred years ago, many Americans died in their mid-fifties. Today, we can expect to live into our seventies and eighties. In the U.S., as in many other countries, women give birth for the first time at older ages than they did several decades ago, but the age at which women lose their fertility has not budged: by forty-five, a persons chances of having a pregnancy without assisted reproductive technology are exceedingly low.

Biologists have theories, none of them conclusive, about why women have such a sharp decline in fertility at midlife, and why ovaries age at least twice as fast as the other organs in the body. Deena Emera, an evolutionary geneticist and the author of a forthcoming book about evolution and the female body, told me that the vast majority of female mammals, including chimpanzees, maintain the ability to get pregnant for most of their lives. Elephants, which can live up to seventy years, can conceive and give birth into their sixth decade. Human females share their long post-reproductive life span with only a few other mammals, mostly species of toothed whales. We are connected in this strange and frustrating reality with narwhals, belugas, and orcas. Theres much debate, if not a definitive answer, about why.

In the U.S., according to census data, the number of births to women under the age of twenty-five has dropped significantly since 1990; an increase in births to women over thirty-five has not compensated for the decline. The United Nations has estimated that in 2019 nearly half the global population lived in countries with below-replacement fertility rates, which the U.N. defines as fewer than 2.1 births per woman. (In our country, population growth is also driven by immigration.) While the over-all growth in human population is not anticipated to plateau until the mid-twenty-eighties, economists say that aging populations in countries with fewer children can affect, among other things, the continued growth of economies, the provision of health care, and the funding of pension systems. Although there are also social and environmental benefits to a decrease in the global population, many countries are recognizing that they can no longer take a passive approach to fertility issues.

In recent years, the science of extending female reproductive longevity has seen a new flurry of interest, and biotech companies are attempting to begin clinical trials of a number of therapies, including new I.V.F. techniques and pharmaceuticals. (The research has earned philanthropic attention as wellHayashis and Saitous labs are funded in part by Open Philanthropy, a foundation set up by the Facebook co-founder Dustin Moskovitz and his wife, the former journalist Cari Tuna.) But the ability to make egg cells without human ovaries would apply not only to people who are designated female at birth. This March, Hayashi, who is not currently trying to make a human egg, had another announcement: his lab had repeated the I.V.G. process in mice, but this time it had produced fertilized embryos whose egg cells had been developed using stem cells from male micemice with two dads, as the headline in Nature put it. Futurists have speculated about broader possibilities, such as an embryo formed with the DNA of four people instead of two, or even a so-called unibaby, the result of a person reproducing with herself. In a less hypothetical realm, in-vitro gametogenesis may have applications in livestock breeding, and might one day play a role in preserving endangered speciesa group of scientists, including Hayashi, have been attempting to use the method to generate eggs from the northern white rhinoceros, a species of which only two females remain.

In some circles, I.V.G. is already seen as the future of reproductive science. Bianka Seres, a co-founder of a startup called Conception Biosciences, which is trying to make egg cells from stem cells, told me that I.V.G.along with a related, though more far-fetched, prospect, artificial wombswas a prominent theme at the American Society for Reproductive Medicines annual conference in 2021, hinting at a time when gestation could happen outside the human body. It wasnt Oh, maybe this will happen, she said. It was very factual: when this happens, this is how were going to use it. She and her colleagues believe that one day dozens of egg cells might be generated from a simple biopsy or blood sample, perhaps even one taken from someone who is biologically male. Conception might not be the company that figures out I.V.G., but the prevailing sense is that its only a matter of time before someone does.

In late January, I visited the headquarters of Conception, in Berkeley. The company was founded in 2018, and has since raised almost forty million dollars in venture capital in pursuit of in-vitro gametogenesis. The staff was temporarily based in a single-story co-working space near Aquatic Park, and things had gotten crowded. Conceptions C.E.O., a thirty-one-year-old entrepreneur named Matt Krisiloff, was working from an armchair wedged between two desks. Krisiloff first tweeted about his interest in I.V.G. in 2017. At the time, he was the director of a nonprofit wing of Y Combinator, the startup incubator, established to fund technological research for the benefit of the world, as the company put it. Sam Altman, who was then running Y Combinator, told me that he and Krisiloff were both interested in what he called hard-tech companies that invest a long time in developing a difficult technology first and then dont bring a first product to market for many, many years. Krisiloff had helped out in the early months of OpenAI, which went on to invent ChatGPT, Dall-E, and the transcription service Whisper, an experience he has cited as formative in learning how to set up a research-oriented company with an ambitious end goal.

Krisiloff has close-cropped hair and a gap-toothed smile, and on the day of my visit he was dressed in jeans, a black crew-neck sweatshirt, and sneakers made by the Swiss brand On. He does not have a degree in the hard sciencesas an undergraduate, he majored in Law, Letters, and Society at the University of Chicagoand was still in his twenties when he and two scientists founded Conception, which was initially known as Ovid Research. Krisiloffs interest in I.V.G. was partly personal: he is gay, and liked the thought of one day being able to have biological children with a male partner. (Krisiloff once dated Altman; he is now in a relationship with Lucas Harrington, the co-founder of Mammoth Biosciences, which is focussed on the gene-editing technology CRISPR.)

While visiting Hayashis lab in Japan in 2018, Krisiloff met Pablo Hurtado Gonzlez, a Spanish biochemist who was a visiting scholar there. Over dinner at a ramen restaurant in Fukuoka one evening, the mission of Conception began to take shape. Hurtado Gonzlez, who is thirty-two, is also gay, and has a Ph.D. in reproductive health and a particular interest in male-male reproduction. (The bio on his Instagram profile reads Trying to make genetic gaybies at Conception Bioscience.) After placing an ad in Nature, Krisiloff and Hurtado Gonzlez hired their third co-founder, Seres, who was born in Romania and raised in Hungary. She had worked as an embryologist at a fertility clinic in England before completing her Ph.D. at Cambridge University under Melina Schuh, a German cell biologist who is an expert in meiosis, the type of cell division unique to reproductive cells, which leads to the production of eggs and sperm. Coming from I.V.F., in-vitro gametogenesis was the single most important solution to not having enough eggs, Seres told me. Seres, who is thirty-six, has a daughter conceived without assisted reproductive technology, but her experience working at fertility clinics had made the issue personal to her: she had seen many patients with infertility issues for which no clear cause could be found.

Krisiloff had secured an initial million dollars from Hydrazine Capital, a fund, co-founded by Altman, in which he was an investor. (Conceptions investors now include Jaan Tallinn, the founder of Skype, and Laura Deming, who has a fund devoted to technologies that target the aging process to treat disease.) At first, Conceptions plan was more modest: to try to bring undeveloped eggs from a human to maturation in vitro. But a conversation with a surgeon convinced Krisiloff that immature eggs would be too difficult to extract. One of our investors gave us really good advice, like, Hey, if in-vitro gametogenesis is the main thing you care about, you can probably go surprisingly far if you just choose to focus on that rather than defer it for later, Krisiloff said. That changed our trajectory.

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The Future of Fertility - The New Yorker

Schizophrenia: How blood vessel growth in the brain may be a factor – Medical News Today

Schizophrenia is a chronic mental disorder. Its symptoms can include disorganized speech, delusions and hallucinations.

About 24 million people have schizophrenia worldwide, less than 1% of the adult population.

What causes the condition remains unknown. Researchers suspect that a combination of genetic, physical, psychological, and environmental factors may play a role.

A growing amount of evidence suggests that schizophrenia may arise from an immune response in the brain.

Understanding more about how immune cells work in the brain in people with schizophrenia could lead to the development of treatments for the condition.

Recently, researchers investigated the role of astrocytes in the development of schizophrenia.

Astrocytes are glial cells a type of cell that support neurons that are found in the nervous system. They play a major role in immunity by secreting immune proteins known as cytokines. They also modulate the formation of new blood vessels in the brain known as vascularization- at the blood-brain barrier.

We know that glial cells are very important for antioxidant and inflammatory responses in the central nervous system, Dr. Andrew Farah, a psychiatrist at Novant Health in North Carolina, told Medical News Today.

Schizophrenia and untreated psychosis involve an inflammatory response, so the theory has long held that perhaps these brains are less well equipped to deal with inflammation, he added.

In a new study published in the journal Molecular Psychiatry, researchers found that astrocytes may increase inflammation and affect how blood vessels grow in the brain.

Dr. Michael McGrath, a psychiatrist and medical director of the Ohana Addiction Treatment Center in Hawaii who was not involved in the study, told Medical News Today:

This study adds to the growing research indicating that inflammation is involved in schizophrenia, he said. The process of inflammation is very complex and this study adds to the details that may lead to specific targeted anti-inflammatory treatments for biological psychiatric conditions such as schizophrenia.

For the study, the researchers extracted skin samples from three people with schizophrenia and four people without the condition.

They then reprogrammed the cells to become induced pluripotent stem cells (iPSCs) and used them to produce neurons and astrocytes.

Next, the researchers analyzed the proteins in each sample. They found that samples from those with schizophrenia contained higher levels of proinflammatory cytokines.

They also contained different levels of other proteins that indicated less vascularization.

After this, the researchers placed the astrocytes into the vascular region of fertilized chicken eggs to observe how they affect blood vessel formation.

They found that astrocytes from people with schizophrenia produced less vascularization. The same astrocytes also secreted more of a pro-inflammatory cytokine known as interleukin-8 (IL-8).

Astrocytes are known to regulate the immune response in the central nervous system, so its possible that they promote more immature or less efficient vascularization, Pablo Trindade, Ph.D., an adjunct professor at the Federal University of Rio de Janeiro in Brazil and a study author, said in a press release.

Our patient-derived astrocytes secreted more interleukin-8 (IL-8) than the controls. IL-8 is proinflammatory and suspected to be the main agent of the vascular dysfunction associated with schizophrenia, he added.

The study authors noted that their findings demonstrate that astrocytes from those with schizophrenia may alter the thickness of blood vessels in the brain, reducing the passage of metabolites that reach the brain.

They added that astrocytes in people with schizophrenia might alter vascularization in fetal neurodevelopment, leading to early brain circuit malformation and potentially schizophrenia later in life.

First symptoms of schizophrenia most often occur in young adulthood, but this study implies that some of this neuronal dysfunction may be present as early as fetal development, Dr. Stephanie Hartselle, a clinical associate professor of psychiatry at Brown University in Rhode Island who was not involved in the study, told Medical News Today.

This is yet another study indicating that inflammation likely plays an enormous role in brain health and more research in this area may provide ways that medications targeting inflammation may eventually help prevent or treat psychiatric disease, she noted.

Dr. David Merrill, an adult and geriatric psychiatrist and director of the Pacific Neuroscience Institutes Pacific Brain Health Center at Providence Saint Johns Health Center in California, told Medical News Today:

This study was conducted in cells derived from just three patients with schizophrenia. It remains to be seen if the findings will hold in a larger sampling of patients or if the findings might differ depending on the particular case, he said.

Medical News Today spoke with Dr, Omotola K. Ajibade, a psychiatry resident at Ocean University Medical Center in New Jersey who was not involved in the study, about its limitations.

The authors rightly point out this study is hamstrung by its small sample size, he said. While the results may not be generalizable to broader populations of those suffering with schizophrenia, they do pose a lot of interesting avenues for future research.

Additionally, many of the experiments were run in cultured media, which is a good approximation for certain cellular environments, but it cant always replicate the complexity seen in whole organisms, he noted.

Raphael Wald, Psy.D., a neuropsychologist at Marcus Neuroscience Institute, part of Baptist Health South Florida, who not involved in the study, also told MNT:

This study focuses on abnormalities at the cellular level. It does not necessarily point us to a direct cause of specific behavioral abnormalities that are expressed in daily life though it certainly suggests a relationship.

MNT also spoke with Emily Treichler, Ph.D., LCP, a licensed clinical psychologist who also was not involved in the study. She noted that while the study helps understand one component of schizophrenia, many other factors play a role too.

Once we zoom back out we can see that yes, inflammation is important, and so are genetics, the gut microbiome, perinatal development, early life experiences, and so much more, she said. Its a complex picture, and its likely to look different depending on the person. There isnt necessarily anything to do at this point in terms of treatment, but folks who have questions about inflammation can talk to their doctors, for example about anti-inflammatory diets.

When asked what these findings may mean for treating schizophrenia, John Cottone, Ph.D., a psychologist in New York who was not involved in the study, told MNT:

If the findings do legitimately identify faulty astrocytes and immature blood vessels as mediators, leading to the pathology of schizophrenia, this opens a broad new area for early detection of the disease and new treatment approaches, perhaps using stem cell treatments, among others.

To this point, the causal factors leading to schizophrenia on both a genetic and neurological level have focused on broader, nonspecific factors, but these findings identify more specific problems in neurodevelopment, which can yield more specific treatments and preventative measures, he concluded.

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Schizophrenia: How blood vessel growth in the brain may be a factor - Medical News Today

Propulsion of Osteoarthritis Pipeline as Novel and Extensive 130+ … – Digital Journal

PRESS RELEASE

Published April 19, 2023

DelveInsights, Osteoarthritis Pipeline Insight 2023 report provides comprehensive insights about 130+ companies and 130+ pipeline drugs in the Osteoarthritis pipeline landscape. It covers the Osteoarthritis pipeline drug profiles, including Osteoarthritis clinical trials and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Key Takeaways from the Osteoarthritis Pipeline Report

Request a sample and discover the recent breakthroughs happening in the Osteoarthritis Pipeline landscape @Osteoarthritis Pipeline Outlook Report

Osteoarthritis Overview

Osteoarthritis (OA) is the most common form of arthritis. Some people call it degenerative joint disease or wear and tear arthritis. It occurs most frequently in the hands, hips, and knees. Osteoarthritis is most likely to affect the joints that bear most of weight, such as the knees and feet. Joints that the person use a lot in everyday life, such as the joints of the hand, are also commonly affected. The main symptoms of osteoarthritis are pain and sometimes stiffness in the affected joints.

Recent Developmental Activities in the Osteoarthritis Treatment Landscape

For further information, refer to the detailed Osteoarthritis Drugs Launch, Osteoarthritis Developmental Activities, and Osteoarthritis News, click here forOsteoarthritis Ongoing Clinical Trial Analysis

Osteoarthritis Emerging Drugs Profile

Lorecivivint (SM04690) is a small-molecule CLK/DYRK1A inhibitor that modulates Wnt and inflammatory pathways and is in development as a potential disease-modifying osteoarthritis drug. Vehicle-controlled preclinical data suggest that lorecivivint has a dual mechanism of action with three potential effects on joint health: reduction of inflammation, slowing of cartilage breakdown, and generation of cartilage. The drug is currently in Phase III stage of clinical trial evaluation to treat the patients suffering from osteoarthritis

Cynatas CYP-004 MSC product is the subject of a Phase III clinical trial being sponsored by the University of Sydney and funded by an Australian Government National Health and Medical Research Council (NHMRC) competitive Project Grant in addition to in-kind contributions from participating institutions. Cynata will supply Cymerus MSCs for use in the trial and will not be required to contribute any cash to fund the project. The clinical trial commenced in late 2020 and is entitled Stem Cells as a symptom- and strUcture-modifying Treatment for medial tibiofemoral OsteoaRthritis (SCUlpTOR): a randomised placebo-controlled trial

JTA-004 is Bone Therapeutics next generation of intra-articular injectable, which is currently in phase III development for the treatment of osteoarthritic pain in the knee. Consisting of a unique patented mix of plasma proteins, hyaluronic acid - a natural component of knee synovial fluid, and a fast-acting analgesic, JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain. In a phase II study involving 164 patients, JTA-004 showed an improved pain relief at 3 and 6 months compared to Hylan G-F 20, the global market leader in osteoarthritis treatment.

SMUP-IA-01, SMUP allogeneic umbilical cord blood-derived mesenchymal stem cells, is currently under development for the treatment and prevention of Osteoarthritis. In SMUP-IA-01s phase I clinical trials in Korea, 12 patients with knee osteoarthritis were given a single injection into their knee joint cavity at Seoul National University Hospital. The response to the drug was then evaluated for 6 months, and the results were shown to demonstrate the safety and improvement of joint function and pain.

TTAX03 is a sterile, lyophilized and micronized particulate human Amniotic and umbilical cord co product manufactured using aseptic processing followed by terminal sterilization by gamma irradiation in compliance with current Good Tissue Practices (cGTP) and current Good Manufacturing Practices (cGMP) to preserve extracellular matrices and growth factors/cytokines therein without any living cells. TTAX03 is currently being investigated in Phase II stage of development for the treatment of patients with knee osteoarthritis

Osteoarthritis Pipeline Therapeutics Assessment

There are approx. 130+ key companies which are developing the Osteoarthritis emerging therapies. The Osteoarthritis companies which have their Osteoarthritis drug candidates in the most advanced stage, i.e phase III include Biosplice Therapeutics

Find out more about the Osteoarthritis Pipeline Segmentation, Therapeutics Assessment, and Osteoarthritis Emerging Drugs @Osteoarthritis Treatment Landscape

Scope of the Osteoarthritis Pipeline Report

Dive deep into rich insights for drugs for Osteoarthritis Pipeline Companies and Therapies, click here @Osteoarthritis Unmet Needs and Analyst Views

Table of Content

Got Queries? Find out the related information on Osteoarthritis Mergers and acquisitions, Osteoarthritis Licensing Activities @Osteoarthritis Emerging Drugs, and Recent Trends

About Us

DelveInsight is a Business Consulting and Market research company, providing expert business solutions for the healthcare domain and offering quintessential advisory services in the areas of R&D, Strategy Formulation, Operations, Competitive Intelligence, Competitive Landscaping, and Mergers & Acquisitions.

Media ContactCompany Name: DelveInsight Business Research LLPContact Person: Yash BhardwajEmail: Send EmailPhone: 9193216187Address:304 S. Jones Blvd #2432City: Las VegasState: NVCountry: United StatesWebsite: https://www.delveinsight.com/

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Propulsion of Osteoarthritis Pipeline as Novel and Extensive 130+ ... - Digital Journal

Results of Study on Cryopreserved Hematopoietic Stem Cell Grafts … – GlobeNewswire

MINNEAPOLIS, April 18, 2023 (GLOBE NEWSWIRE) -- CIBMTR (Center for International Blood and Marrow Transplant Research) announced that the results of a multi-center observational study, around the impact of cryopreserved hematopoietic stem cell (HSC) grafts on patient survival rates were published in Blood Advances, a peer-reviewed open access medical journal published by the American Society of Hematology. The study showed that the shift in clinical practice to cryopreserved products necessitated during the pandemic did not adversely impact one-year overall survival. The CIBMTR is a research collaboration between the National Marrow Donor Program (NMDP)/Be The Match and the Medical College of Wisconsin (MCW).

The COVID-19 pandemic provided an unprecedented opportunity to study the impact of cryopreservation on clinical outcomes since the vast majority of patients received cryopreserved grafts for safety reasons at the onset of the pandemic. While it was comforting to find there were no differences in overall survival, there were more graft failures and relapses compared to fresh grafts, said Steven Devine, MD, Chief Medical Officer, NMDP/Be The Match and Senior Scientific Director, CIBMTR NMDP. These findings demonstrate that fresh grafts are preferred but that cryopreserved grafts do appear to be a good alternative during a crisis or if due to logistical reasons it could make the difference between transplant and no transplant.

The COVID-19 pandemic necessitated a substantial increase in the use of cryopreserved HSC grafts from both related and unrelated donors to ensure patients had a graft available prior to the start of conditioning for HCT. This cryopreservation necessitation was due to increased logistical challenges from international travel bans and fluctuating donor availability due to unpredictable health. However, pre-pandemic data on the impact of cryopreservation on post-transplant outcomes was limited. At the onset of the pandemic, the CIBMTR rapidly completed three retrospective analyses of outcomes in recipients of cryopreserved compared to fresh grafts administered prior to the pandemic with varying results and in all cases lack of a unifying rationale for use of cryopreservation.

The NMDP mandated cryopreservation of their facilitated collections at that onset of the pandemic and many centers adopted a similar approach for locally collected products. Thus, early in the pandemic the vast majority of patients received planned cryopreserved allografts allowing CIBMTR to successfully evaluate early post-HCT clinical outcomes in patients reported to the CIBMTR database who received a first allogeneic HCT using cryopreserved grafts. The study subjects were US patients receiving fresh (March-August 2019) or cryopreserved (March-August 2020) bone marrow or peripheral blood stem cell transplants from matched related or unrelated donors. This study included 1,543 and 2,499 recipients of cryopreserved and fresh products, respectively.

The results demonstrated that the shift in clinical practice to cryopreserved products necessitated during the pandemic did not adversely impact one-year post-transplant overall survival, non-relapse mortality, acute graft-versus-host disease (GVHD), or GVHD-free, relapse-free survival in recipients of cryopreserved versus fresh allografts. However, the study did find an adverse impact of cryopreservation on disease-free survival due to a higher risk of relapse. There was also an increased risk of primary graft failure following cryopreservation. One advantage observed with cryopreserved grafts was a decreased risk of chronic GVHD consistent with results previously described in a single center study published by Dana Farber Cancer Institute. Based on these results the study team concluded that fresh grafts are recommended, and that cryopreservation should be considered an option for patients when infusion of fresh grafts are not feasible.

NMDP/Be The Match and its research group CIBMTR are dedicated to providing clinical teams caring for HCT recipients with data that can inform their clinical practice, ensuring that patients thrive following transplant, said Amy Ronneberg, Chief Executive Officer, NMDP/ Be The Match. We are proud to have taken leadership on this important graft study and to have the results shared broadly in Blood Advances.

National Marrow Donor Program (NMDP)/Be The MatchThe National Marrow Donor Program (NMDP)/Be The Match is the leading global partner working to save lives through cellular therapy. With 35 years of experience managing the most diverse registry of potential unrelated blood stem cell donors and cord blood units in the world, NMDP/Be The Match is a proven partner in providing cures to patients with life-threatening blood and marrow cancers and diseases. Through their global network, they connect centers and patients to their best cell therapy optionfrom blood stem cell transplant to a next-generation therapyand collaborate with cell and gene therapy companies to support therapy development and delivery through Be The Match BioTherapies. NMDP/Be The Match is a tireless advocate for the cell therapy community, working with hematologists/oncologists to remove barriers to consultation and treatment, and supporting patients through no-cost programs to eliminate non-medical obstacles to cell therapy. In addition, they are a global leader in research through the CIBMTR (Center for International Blood and Marrow Transplant Research)a collaboration with Medical College of Wisconsin, investing in and managing research studies that improve patient outcomes and advance the future of care.

CIBMTR (Center for International Blood and Marrow Transplant Research)Center for International Blood and Marrow Transplant Research is a nonprofit research collaboration between the National Marrow Donor Program (NMDP)/ Be The Match, in Minneapolis, and the Medical College of Wisconsin, in Milwaukee. The CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centers, and a unique database of long-term clinical data for more than 630,000 people who have received hematopoietic cell transplantation and other cellular therapies. Learn more at cibmtr.org.

Media Contacts

NMDP/Be The MatchClarity Quest, 877-887-7611 Bonnie Quintanilla, bonnie@clarityqst.comPhyllis Grabot, phyllis@clarityqst.com

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Results of Study on Cryopreserved Hematopoietic Stem Cell Grafts ... - GlobeNewswire

QUINCY UNIVERSITY TO HOST SIXTH ANNUAL ACADEMIC … – Quincy University

Quincy University will host its sixth annual Academic Symposium April 19 21 at the Connie Niemann Center for Music, South Auditorium, QU North Campus, 1700 Seminary Rd. This event is free and open to the public.

Students will present their original research April 19 and April 20 from 10 a.m.-1:30 p.m. Multiple poster presentations and special media presentations will be displayed Friday, April 21 from 10 a.m.-12 p.m. Presentations will be in the Connie Niemann Center for Music, South Auditorium except for one senior retrospective exhibition in Gray Gallery in Brenner Library scheduled at 1:30 p.m. on April 20.

The QU Academic Symposium will feature the work of 51 undergraduate students, with the support of 13 mentors, representing the following schools: School of Science & Technology, School of Humanities, School of Fine Arts and Communication, School of Education and Human Services and the Oakley School of Business. The Academic Symposium includes 14 platform presentations and 19 poster and special media presentations.

Academic Symposium awards presentations will begin at 1 p.m. on April 21.

During lunch on Friday, April 21, two keynote speakers will address presenters and attendees: Bridget Brengle, MA, Senior Associate Scientist in the Bioassay and Impurity Testing Group at Pfizer, and Maureen Dolan, PhD, Director of Biotechnology Program and Associate Professor of Molecular Biology at Arkansas State University.

Bridget Hunkins Brengle 19 will present From Sonic Hedgehog to Pharmaceutics (and everything in between). Brengle will talk about her undergraduate research under Dr. Michele Combs while a student at QU, how her research took her to Washington University and what she studied there, and what her career entails working as a scientist at Pfizer.

Brengle graduated from Quincy University with a major in Biology. The day after graduation, she began as a research technician at Washington University-St. Louis. A love of scientific outreach and career development changed her path in her third year of her Developmental, Regenerative, and Stem Cell Biology program. She completed her masters work and began at Pfizer in November of 2022 where she combines her talents at the bench and passion for medical science.

Dr. Maureen Dolan 87 will present Interdisciplinary Student-driven Undergraduate Research Launching Plastic-eating Waxworms into Space. Dolan will talk about her research project with a team of Arkansas State undergraduate researchers testing if Galleria mellonella larva, commonly known as the waxworm, may offer a solution to plastic waste buildup in space. The results of their study could pave the way for novel, more sustainable methods of plastic waste management not only for long-term space travel to the Moon or Mars but also for here on Earth.

Dolan graduated from Quincy College in 1987 with a double major in Biology and Chemistry. She earned her MS in Biochemistry from Iowa State University and a PhD in Molecular Biology & Biochemistry from the University of Florida. Her non-traditional research career path has opened opportunities to be involved in developing new and innovative DNA-based tests for the food industry, and bioengineering plants to become living factories for making protein-based medicines used to improve the health of agriculture animals and people.

The Academic Symposium aims to prepare academically talented students for professional schools, to reward academic achievement, to provide an opportunity for academic competition among students and to offer a platform for interaction among major programs.For more information, contact Caitlin Deskins, PhD, at deskica@quincy.edu.

Founded in 1860 by Franciscan friars, Quincy University is a small Catholic universityemphasizing the sciences, liberal arts and the professions. Quincy University offers undergraduate, graduate and adult education programs integrating practical experience and Franciscan values. Faculty and advisors work with students to design customized success plans to help them graduate on time, find their passion and prepare them for life. QU is a member of NCAA Division II for intercollegiate athletics. For more information, please visit http://www.quincy.edu or contact the Office of Community Relations at (217) 228-5275 or communityrelations@quincy.edu. Quincy University. Success by Design.

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QUINCY UNIVERSITY TO HOST SIXTH ANNUAL ACADEMIC ... - Quincy University

"Sweet" Research Sheds Light on Glucose Metabolism in Neurons – Neuroscience News

Summary: Neurons in the brain directly metabolize glucose to function normally, contrary to previous beliefs that glial cells metabolized the sugar and indirectly fuel neurons. The findings could provide insights into the development of new therapeutic approaches for neurodegenerative diseases like Alzheimers and Parkinsons, where the brains uptake of glucose decreases in the early stages of the diseases.

Source: Gladstone Institute

The human brain has a sweet tooth, burning through nearly one quarter of the bodys sugar energy, or glucose, each day. Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) have shed new light on exactly how neuronsthe cells that send electrical signals through the brainconsume and metabolize glucose, as well as how these cells adapt to glucose shortages.

Previously, scientists had suspected that much of the glucose used by the brain was metabolized by other brain cells called glia, which support the activity of neurons.

We already knew that the brain requires a lot of glucose, but it had been unclear how much neurons themselves rely on glucose and what methods they use to break the sugar down, saysKen Nakamura, MD, PhD,associate investigator at Gladstone and senior author of thenew study published in the journalCell Reports.Now, we have a much better understanding of the basic fuel that makes neurons run.

Past studies have established that the brains uptake of glucose is decreased in the early stages of neurodegenerative diseases like Alzheimers and Parkinsons. The new findings could lead to the discovery of new therapeutic approaches for those diseases and contribute to a better understanding of how to keep the brain healthy as it ages.

Simple Sugar

Many foods we eat are broken down into glucose, which is stored in the liver and muscles, shuttled throughout the body, and metabolized by cells to power the chemical reactions that keep us alive.

Scientists have long debated what happens to glucose in the brain, and many have suggested that neurons themselves dont metabolize the sugar. They instead proposed that glial cells consume most of the glucose and then fuel neurons indirectly by passing them a metabolic product of glucose called lactate. However, the evidence to support this theory has been scantin part because of how hard it is for scientists to generate cultures of neurons in the lab that do not also contain glial cells.

Nakamuras group solved this problem using induced pluripotent stem cells (iPS cells) to generate pure human neurons. IPS cell technology allows scientists to transform adult cells collected from blood or skin samples into any cell type in the body.

Then, the researchers mixed the neurons with a labeled form of glucose that they could track, even as it was broken down. This experiment revealed that neurons themselves were capable of taking up the glucose and of processing it into smaller metabolites.

To determine exactly how neurons were using the products of metabolized glucose, the team removed two key proteins from the cells using CRISPR gene editing. One of the proteins enables neurons to import glucose, and the other is required for glycolysis, the main pathway by which cells typically metabolize glucose. Removing either of these proteins stopped the breakdown of glucose in the isolated human neurons.

This is the most direct and clearest evidence yet that neurons are metabolizing glucose through glycolysis and that they need this fuel to maintain normal energy levels, says Nakamura, who is also an associate professor in the Department of neurology at UCSF.

Fueling Learning and Memory

Nakamuras group next turned to mice to study the importance of neuronal glucose metabolism in living animals. They engineered the animals neurons but not other brain cell typesto lack the proteins required for glucose import and glycolysis. As a result, the mice developed severe learning and memory problems as they aged.

This suggests that neurons are not only capable of metabolizing glucose, but also rely on glycolysis for normal functioning, Nakamura explains.

Interestingly, some of the deficits we saw in mice with impaired glycolysis varied between males and females, he adds. More research is needed to understand exactly why that is.

Myriam M. Chaumeil, PhD,associate professor at UCSF and co-corresponding author of the new work, has been developing specialized neuroimaging approaches, based on a new technology called hyperpolarized carbon-13, that reveal the levels of certain molecular products. Her groups imaging showed how the metabolism of the mices brains changed when glycolysis was blocked in neurons.

Such neuroimaging methods provide unprecedented information on brain metabolism, says Chaumeil. The promise of metabolic imaging to inform fundamental biology and improve clinical care is immense; a lot remains to be explored.

The imaging results helped prove that neurons metabolize glucose through glycolysis in living animals. They also showed the potential of Chaumeils imaging approach for studying how glucose metabolism changes in humans with diseases like Alzheimers and Parkinsons.

Finally, Nakamura and his collaborators probed how neurons adapt when they are not able to get energy through glycolysisas might be the case in certain brain diseases.

It turned out neurons use other energy sources, such as the related sugar molecule galactose. However, the researchers found that galactose was not as efficient a source of energy as glucose and that it could not fully compensate for the loss of glucose metabolism.

The studies we have carried out set the stage for better understanding how glucose metabolism changes and contributes to disease, says Nakamura.

His lab is planning future studies on how neuronal glucose metabolism changes with neurodegenerative diseases in collaboration with Chaumeils team, and how energy-based therapies could target the brain to boost neuronal function.

The first authors are Huihui Li and Yoshitaka Sei of Gladstone and Caroline Guglielmetti of UCSF. Other authors are Misha Zilberter, Lauren Shields, Joyce Yang, Kevin Nguyen, Neal Bennett, Iris Lo, and Yadong Huang of Gladstone; Lydia M. Le Page, Brice Tiret, Xiao Gao, and Martin Kampmann of UCSF; Talya L. Dayton and Matthew Vander Heiden of Massachusetts Institute of Technology; and Jeffrey C. Rathmell of Vanderbilt University Medical Center.

Funding: The work was supported by the National Institutes of Health (RF1 AG064170, R01 AG065428, AG065428-03S1, R01 NS102156, R21 AI153749 and RR18928), National Institute on Aging (R01 AG061150, R01 AG071697, P01 AG073082, R01 CA168653, R35 CA242379, R01 DK105550), the UCSF Bakar Aging Research Institute, the Alzheimers Association, a Bright Focus Foundation Award, a Berkelhammer Award for Excellence in Neuroscience, and a Chan Zuckerberg Initiative Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.

Summary was written with the assistance of ChatGPT AI technology

Author: Julie LangelierSource: Gladstone InstituteContact: Julie Langelier Gladstone InstituteImage: The image is in the public domain

Original Research: Open access.Neurons require glucose uptake and glycolysis in vivo by Ken Nakamura et al. Cell Reports

Abstract

Neurons require glucose uptake and glycolysis in vivo

Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites.

To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits.

Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism.

Therefore, neurons metabolize glucose through glycolysisinvivoand require glycolysis for normal function.

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"Sweet" Research Sheds Light on Glucose Metabolism in Neurons - Neuroscience News

11 Incredible Animals That Regenerate – AZ Animals

There are countless natural wonders around the globe. They are too numerous to count, and we humans never get tired of the surprises nature has in store for us.

In addition to all the marvels, it is worthwhile to consider if we would be able to regrow a lost limb or damaged organ. These skills may seem like something out of a sci-fi film, but they are really found in the animal kingdom. Although the majority of animals lack these skills, there are some animals that regenerate limbs, organs, and other body parts with ease. These few organisms could help us understand how regeneration works in their species and possibly even ours. Who knows? Maybe science could use these fascinating creatures to one day make regeneration possible for humans. In fact, many of the animals on this list are currently being studied for their potential use in regenerative medicine for humans.

Pseudoscience aside, lets take a look at some real, living animals that regenerate! But first, lets ask a very important question: Why cant humans regenerate?

So how exactly can the species listed in this article regenerate? And why are the majority of creatures, including humans and other mammals, so terrible at regeneration? According to science, thats still a confounding topic today. There are a few competing theories, and the scientific community is still undecided.

One theory relates to how our immune system has evolved. Mammals and birds, which have very high immunity levels, cannot regrow their legs, fingers, and other body parts. This could be a result of the immune systems desire to avoid cancerous tumor growth and the fact that the molecular pathways of regeneration and tumor growth are identical, including the usage of stem cells. Therefore, evolution guarantees that these animals wont have as many cancers, but they also wont regenerate.

Research on the African spiny mouse, a species of mouse that can regrow its skin and hair after an injury, lends credence to this notion. According to a few studies, the skin these animals regenerate doesnt appear to include any immune cells called macrophages. Macrophages are white blood cells stimulated by the bodys immune system. Because of this, a large portion of the scientific community believes that immunity and regeneration are somehow related.

If and when humans are able to use any of these regeneration abilities will depend on advancements in our understanding of how and why certain animals can regenerate while others cannot. Doctors, scientists, and other professionals involved in the field of regenerative medicine should pay particular attention to this. Humans, for instance, cannot create new fingers or legs, but during fetal development, these genes all help the formation of our fingers or legs, and they are also present in starfish and hydra, which are regenerative animals mentioned later on in this guide.

Perhaps a method to activate these genes during postnatal development to restore limbs will emerge. Maybe mankind will find some way to make human regeneration possible. For now, though, its all still a pretty big mystery.

Now that we understand a bit more about regeneration in animals, lets take a look at a few animals that regenerate!

Classification: Asteroidea class

Sea stars have the capacity to regenerate their tube feet and ray arms after accidents. Most sea stars, also known as starfish, have five limbs, but some have as many as 40. Because the majority of their essential organs are located in their arms, certain sea stars can regenerate complete bodies or a new sea star merely from a section of a severed limb. When predators catch them, they can also release or drop one arm.

Starfish are capable of developing a new body from a lost limb in addition to a new limb. The original starfish can be broken apart into several new ones. Fission is a term used to describe this type of asexual reproduction. Fission occurs when the starfish loses one or more of its limbs and its central disc splits into two parts. From there, another sea star is created that is genetically identical to the parent plant.

iStock.com/Damocean

Classification: Ambystoma mexicanum

Axolotls are a type of aquatic salamander that have remarkable regeneration powers. They can grow new skin, limbs, organs, or just about any other part of the body. Axolotls live permanently underwater because they never develop lungs and instead retain their gills. Axolotls can regenerate limbs and organs flawlessly and without leaving any scarring, which is even more astounding. In as short as three weeks, they can repeat this as often as required.

The Axolotl is the only vertebrate, regardless of age, that can regenerate a number of its body parts. However, it does not use its stem cell population to do this. Instead, it takes advantage of a process called dedifferentiation. When their bodies are damaged, neighboring undifferentiated cells help them form a stub known as a blastema.

These animals basically turn back the clock on their bodys aged cells so they may begin to behave like embryonic or stem cells, despite the fact that they are not stem cells. They havent undergone differentiation since they fall midway between stem cells and adult cells, but they are already pre-programmed for what they will become. Many other creatures with the potential to regenerate prefer this method of regeneration, which is known as epimorphic regeneration. Salamanders and terrestrial lizards also employ this strategy. The starfish does as well, and occasionally it can develop a completely new body from just one arm.

Spok83/Shutterstock.com

Classification: Selachimorpha superorder

Now this is a surprising entry! Sharks can renew their dental structures, but they cannot restore their organs or other bodily components like other animals on this list can. Over the course of a lifetime, they lose at least 30,000 teeth. However, each one may regenerate in a matter of days or months. Over the course of its lifetime, a shark can regenerate missing teeth up to 50 times.

A sharks ability to regenerate teeth might take anywhere from a few days and several months. Dentistry could undergo a real revolution if scientists can figure out how this regeneration process works!

Alessandro De Maddalena/Shutterstock.com

Classification: Planaria genus

Flatworms known as planarians have a remarkable capacity for self-regeneration. In just a few weeks, one might create two planarians by slicing one in half; each half would quickly fill in the gaps in a very short amount of time.

One of the most remarkable regeneration techniques in the animal kingdom is used by these flatworms. These aquatic worms are invertebrates, and even after losing up to 90% of their bodies to damage, they can completely rebuild their whole bodies. They can even grow their head back if they are decapitated.

These creatures regenerate via a stem cell-mediated process. They have a population of pluripotent stem cells that are constantly present in the body and are intermittently replacing damaged cells. These cells are effectively tasked to repair the missing structure when a significant amputation occurs, no matter how severe. Sea squirts, which are a type of marine invertebrate, also employ this method.

Rattiya Thongdumhyu/Shutterstock.com

Classification: Urodela order

The salamander is an amphibian with short legs and a tail. The number of salamander species that we currently know of exceeds 700. Although all salamander species are capable of some degree of regeneration, certain species are more capable than others. Following the removal of the old tail to frighten away predators, certain salamanders can develop a new tail in a few weeks. The replacement limb performs all functions just like the old one.

Salamanders have earned praise for being masters of regeneration because of their astonishing capacity to create new tissues, organs, and even whole body parts, like their limbs. The methods by which salamander cells, tissues, and organs detect and restore missing or damaged pieces can provide key insights into the world of regenerative medicine.

iStock.com/Wirestock

Classification: Hydra genus

The hydra is a type of freshwater jellyfish that prefers to adhere to rocks throughout its life, similar to an anemone. These unique animals often go through a process of regeneration called morphallaxis.

In essence, these animals can shuffle their cells around and restructure whats left of the tissue, creating a miniature replica that is completely formed and has all of the necessary features. They can also take this regeneration technique a step further. The mechanism of how they regenerate can change depending on how they are harmed. If they sustain more severe wounds, the hydra will also engage in the same process as the Axolotl, whereby a fresh batch of cells proliferates and dedifferentiates to fill in the gaps in the missing structure.

Lebendkulturen.de/Shutterstock.com

Classification: Ascidiacea class

Tunicates, sometimes referred to as sea squirts, are renowned for their extraordinary ability to regenerate their whole body. A sea squirt can restructure its residual tissues and rebuild a completely functioning body in a couple of days after being damaged or losing a large chunk of its body.

Genes that regulate cell division and differentiation are activated during the regeneration process in sea squirts. In order to create the required tissues and organs, the cells must then rearrange and differentiate. Sea squirts are a model organism for researching the genetic and molecular pathways of regeneration because of their exceptional capacity for regeneration. This capacity could also provide new ideas for regenerative medicine, like many of the entries on this list.

Samuel Chow / Creative Commons

Classification: Slender danios

Even as older adults, zebrafish have the ability to regenerate their fins, spinal cord, retinas, heart, kidneys, and the telencephalon, the most advanced portion of the frontal lobe of the brain. It appears that different organs have different pathways for regeneration in this creature as well. The Axolotl or the starfish have comparable processes used for fin regeneration. However, just like the flatworm, regeneration of the zebrafishs telencephalon relies on stem cells to intervene and ensure the fishs brain is properly repaired.

Ian Grainger/Shutterstock.com

Classification: Astyanax mexicanus

Mexican tetras can repair heart tissue, much like zebrafish. Or rather, surface fish of this species can; populations of fish from caves no longer possess this ability. After damage, cave populations hearts develop scarring similar to how a humans heart would. According to the latest research on this species, tetras have unregulated versions of many genes.

The surface specimens of the Mexican tetra, which live in rivers and streams, can regenerate tissue without leaving scars. Researchers are hoping that their research on the Mexican tetra will help them make advances in the treatment of cardiovascular disease. The Mexican tetra is not the only fish capable of regenerating heart tissue, though. Also capable of regenerating its heart with minimal to no scarring is the zebrafish.

Kuttelvaserova Stuchelova/Shutterstock.com

Classification: Chamaeleonidae family

Chameleons are extremely fascinating creatures that are widely renowned for their extraordinary ability to alter their color in order to fit in with their surroundings. Chameleons can also grow new tails and limbs, in addition to their other abilities. During the healing process, they can also repair damaged skin and nerves.

A chameleon can sprout a new tail if it loses its original one. A blastema, or a collection of undifferentiated cells that will eventually become the new tail, is created throughout the process. Cells from the tail stump that dedifferentiate, or go back to a less specialized state, create the blastema. Following cell division and differentiation, the cells form the diverse tissues of the new tail. This remarkable capacity for regeneration is displayed by a few other species and is a subject of current study in the field of regenerative medicine.

Lauren Suryanata/Shutterstock.com

Classification: Cervidae family

Deer antlers are the only organ in mammals that can totally regenerate. They lose their antlers each year and then re-grow into enormous, branching structures of bone and cartilage that are utilized for combat and exhibition.

Scientists are using the regeneration of antlers, which is started and maintained by stem cells generated from the neural crest, to mimic and research the regeneration of other animal organs. Only male deer (except for caribou) have antlers. Male deer grow antlers in order to compete with other males for females and to find food in the snow. Antlers develop at a very rapid rate of roughly one-fourth of an inch every day.

Bob Keefer/Shutterstock.com

There are many animals that regenerate around the world. The animals weve listed above are just a few. Hopefully, one day science will be able to harness the processes of regeneration that these animals possess to apply to humans.

See the rest here:
11 Incredible Animals That Regenerate - AZ Animals

Healing the unhealable: New approach helps bones mend themselves – Newswise

Newswise Young babies and newborn mice can naturally heal damage to the bones that form the top of the skull, but this ability is lost in adults. In a new study published inProceedings of the National Academy of Sciences, University of Pittsburgh researchers developed a novel approach that promoted bone regeneration in mice without implantation of bone tissue or biomaterials.

The technique uses a device similar to an orthodontic wire used to realign teeth to carefully stretch the skull along its sutures, activating skeletal stem cells that reside in these wiggly seams. In adult mice, the technique repaired damage to the skull that otherwise would not have healed on its own.

Our approach is inspired by babies because they have an amazing ability to regenerate bone defects in the calvarial bones that make up the top of the skull, said senior author Giuseppe Intini, D.D.S., Ph.D., associate professor of periodontics and preventive dentistry at thePitt School of Dental Medicine,member of theMcGowan Institute for Regenerative Medicineand an investigator atUPMC Hillman Cancer Center. By harnessing the bodys own healing capacity with autotherapies, we can stimulate bone to heal itself. We hope to build on this research in the future to develop novel therapies for people.

Trauma, congenital defects and surgery to treat cancer or other diseases are common causes of damage to the skull. After people reach the age of about 2 years, such injuries dont heal on their own.

In babies, the calvarial bones are not completely fused, so the sutures where stem cells reside are still open, said Intini. We wondered whether the unfused sutures had something to do with the bone regenerative capacity observed in babies and hypothesized that we could reverse engineer this in adults by mechanically opening the sutures to activate the stem cell niche and boost stem cell numbers.

In mice which have very similar skull development to humans the researchers used a so-called bone distraction device to carefully apply a controlled pulling force to the calvarial bones, strong enough to slightly widen the sutures but not enough to cause a fracture. Using single-cell RNA sequencing and live-imaging microscopy, they found that the number of stem cells in the expanded sutures of these animals quadrupled.

As a result, mice treated with the device regenerated bone to heal a large defect in the skull.

If you can effectively activate the stem cell niche, you can increase the number of stem cells and sustain regeneration of bone defects, said Intini. Remarkably, we showed that the defect can heal even if its away from the suture.

Although the approach was effective in healing skeletally mature 2-month-old mice, the age that roughly translates to young adulthood in humans, it did not work in 10-month-old, or middle-aged, rodents.

In older mice, the quantity of stem cells in calvarial sutures is very low, so expanding this niche is not as effective in boosting healing capacity, Intini explained. Overcoming this challenge is a focus of research to come.

Current treatments for damage to the skull are usually bone grafts or implantation of biomaterials that act as scaffolds for bone regeneration, but these approaches are not always effective and come with risks, said Intini.

The researchers are investigating how their findings could be used to inform novel therapies in people, not just to heal skull injuries but also fractures in long bones such as the femur. Bone distraction devices are already used to treat certain conditions such as a birth defect called craniosynostosis, in which the calvarial bones fuse too early, so expanding this technique to promote bone regeneration could be a future focus of clinical trials.

Intini and his team are also investigating non-mechanical approaches to activate skeletal stem cells such as medications.

Other authors who contributed to the study were Zahra A. Aldawood, D.M.Sc, of the Harvard School of Dental Medicine and Imam Abdulrahman Bin Faisal University; Luigi Mancinelli, Ph.D., Xuehui Geng, M.D., M.S., Taiana C. Leite, D.D.S., M.S., and Roberta Di Carlo, Ph.D., all of Pitt; Shu-Chi A. Yeh, Ph.D., and Charles P. Lin, Ph.D., both of Massachusetts General Hospital; Jonas Gustafson, of Seattle Childrens Research Institute; Katarzyna Wilk, M.S., Joseph Yozgatian, D.D.S., M.M.Sc., Ph.D., Sasan Garakani, D.D.S., and Seyed Hossein Bassir, D.D.S., D.M.Sc., of the Harvard School of Dental Medicine; and Michael L. Cunningham, M.D., Ph.D., of the Seattle Childrens Research Institute and the University of Washington.

This research was supported by the National Institutes of Healths National Institute of Dental and Craniofacial Research (grants #R00DE021069 and #R01DE026155).

Read the rest here:
Healing the unhealable: New approach helps bones mend themselves - Newswise

Reinforcement learning: From board games to protein design – EurekAlert

image:Examples of protein architectures designed through a software program that uses reinforcement learning. view more

Credit: Ian Haydon/ UW Medicine Institute for Protein Design

Scientists have successfully applied reinforcement learning to a challenge in molecular biology.

The team of researchersdeveloped powerful new protein design software adapted from a strategy proven adept at board games like Chess and Go. In one experiment, proteins made with the new approach were found to be more effective at generating useful antibodies in mice.

The findings, reported April 21 in Science, suggest that this breakthrough may soon lead to more potent vaccines. More broadly, the approach could lead to a new era in protein design.

"Our results show that reinforcement learning can do more than master board games. When trained to solve long-standing puzzles in protein science, the software excelled at creating useful molecules," said senior author David Baker, professor of biochemistry at the UW School of Medicine in Seattle and a recipient of the 2021 Breakthrough Prize in Life Sciences.

"If this method is applied to the right research problems, he said, it could accelerate progress in a variety of scientific fields."

The research is a milestone in tapping artificial intelligence to conduct protein science research. The potential applications are vast, from developing more effective cancer treatments to creating new biodegradable textiles.

Reinforcement learning is a type of machine learning in which a computer program learns to make decisions by trying different actions and receiving feedback. Such an algorithm can learn to play chess, for example, by testing millions of different moves that lead to victory or defeat on the board. The program is designed to learn from these experiences and become better at making decisions over time.

To make a reinforcement learning program for protein design, the scientists gave the computer millions of simple starting molecules. The software then made ten thousand attempts at randomly improving each toward a predefined goal. The computer lengthened the proteins or bent them in specific ways until it learned how to contort them into desired shapes.

Isaac D. Lutz, Shunzhi Wang, and ChristofferNorn, all members of the Baker Lab, led the research. Their teams Science manuscript is titled "Top-down design of protein architectures with reinforcement learning."

"Our approach is unique because we use reinforcement learning to solve the problem of creating protein shapes that fit together like pieces of a puzzle," explained co-lead author Lutz, a doctoral student at the UW Medicine Institute for Protein Design. "This simply was not possible using prior approaches and has the potential to transform the types of molecules we can build."

As part of this study, the scientists manufactured hundreds of AI-designed proteins in the lab. Using electron microscopes and other instruments, they confirmed that many of the protein shapes created by the computer were indeed realized in the lab.

This approach proved not only accurate but also highly customizable. For example, we asked the software to make spherical structures with no holes, small holes, or large holes. Its potential to make all kinds of architectures has yet to be fully explored, said co-lead author Shunzhi Wang, a postdoctoral scholar at the UW Medicine Institute for Protein Design.

The team concentrated on designing new nano-scale structures composed of many protein molecules. This required designing both the protein components themselves and the chemical interfaces that allow the nano-structures to self-assemble.

Electron microscopy confirmed that numerous AI-designed nano-structures were able to form in the lab. As a measure of how accurate the design software had become, the scientists observed many unique nano-structures in which every atom was found to be in the intended place. In other words, the deviation between the intended and realized nano-structure was on average less than the width of a single atom. This is called atomically accurate design.

The authors foresee a future in which this approach could enable them and others to create therapeutic proteins, vaccines, and other molecules that could not have been made using prior methods.

Researchers from the UW Medicine Institute for Stem Cell and Regenerative Medicine used primary cell models of blood vessel cells to show that the designed protein scaffolds outperformed previous versions of the technology. For example, because the receptors that help cells receive and interpret signals were clustered more densely on the more compact scaffolds, they were more effective at promoting blood vessel stability.

Hannele Ruohola-Baker, a UW School of Medicine professor of biochemistry and one of the studys authors, spoke to the implications of the investigation for regenerative medicine: The more accurate the technology becomes, the more it opens up potential applications, including vascular treatments for diabetes, brain injuries, strokes, and other cases where blood vessels are at risk. We can also imagine more precise delivery of factors that we use to differentiate stem cells into various cell types, giving us new ways to regulate the processes of cell development and aging.

This work was funded by the National Institutes of Health (P30 GM124169, S10OD018483, 1U19AG065156-01, T90 DE021984, 1P01AI167966); Open Philanthropy Project and The Audacious Project at the Institute for Protein Design; Novo Nordisk Foundation (NNF170C0030446); Microsoft; and Amgen. Research was in part conducted at the Advanced Light Source, a national user facility operated by Lawrence Berkeley National Laboratory on behalf of the Department of Energy

News release written by Ian Haydon, UW Medicine Institute for Protein Design.

Computational simulation/modeling

Not applicable

Top-down design of protein architectures with reinforcement learning

21-Apr-2023

David Baker, Shunzhi Wang, Isaac D. Lutz, Christoffer Norn, Annie Dosey, Neil P. King, and Andrew J. Borst are inventors on a provisional patent application (63/383,700) submitted by the University of Washington for the design, composition, and applications of the protein assemblies described in this work. The remaining authors declare no competing interests.

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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Reinforcement learning: From board games to protein design - EurekAlert

Tonix Pharmaceuticals Announces Presentations of Pre-Clinical Data on TNX-1700 in Syngeneic Models of Colorectal and Gastric Cancer at the American…

Tonix Pharmaceuticals Holding Corp.

CHATHAM, N.J., April 19, 2023 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a clinical-stage biopharmaceutical company, today announced the presentation of two posters with research results on TNX-1700 (recombinant TFF2 albumin fusion peptide) at the American Association for Cancer Research (AACR) Annual Meeting, held April 14-19, 2023, in Orlando, Fla. Copies of the Companys posters are available under the Scientific Presentations tab of the Tonix website at http://www.tonixpharma.com.

The poster presentation, titled, MDSC-targeted TFF2-MSA suppresses tumor growth and increases survival in anti-PD-1 treated MC38 and CT26.wt murine colorectal cancer models, includes data demonstrating that targeting myeloid-derived suppressor cells (MDSCs) using murine TNX-1700, or mTNX-1700 (TFF2-MSA fusion protein) synergizes with PD-1 blockade therapy in advanced syngeneic mouse models of colorectal cancer. The data show that mTNX-1700 and anti-PD-1 monotherapy each were able to evoke anti-tumor immunity in the MC38 and CT26.wt models of colorectal cancer, and that mTNX-1700 augmented the anti-tumor efficacy of anti-PD-1 therapy in both of these colorectal cancer models.

The poster presentation, titled, MDSC-targeted TFF2-MSA synergizes with PD-1 blockade therapy in diffuse-type gastric cancer, includes data showing that targeting MDSCs using mTNX-1700 synergizes with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of diffuse-type gastric cancer, suggesting combination therapy of mTNX-1700 and PD-1 blockade may also be applicable to gastric cancer.

We believe these data demonstrate that targeting MDSCs using mTNX-1700 provides additive benefits to PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of colorectal and gastric cancer, said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals.

About Trefoil Factor Family Member 2 (TFF2)

Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. The inventor at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells.1 He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-lifein vivoand was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth.2Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment. Dr. Wang presented data at the American Association for Cancer Research (AACR) conference as a collaboration between Tonix and Columbia University in 2020that includes data from a preclinical study which investigated the role of PD-L1 in colorectal tumorigenesis and evaluated the utility of targeting myeloid-derived suppressor cells (MDSCs) in combination with PD-1 blockade in mouse models of colorectal cancer. The data show that anti-PD-1 monotherapy was unable to evoke anti-tumor immunity in this model of colorectal cancer, but mTFF2-CTP augmented the efficacy of anti-PD-1 therapy. Anti-PD-1 in combination with TFF2-CTP showed greater anti-tumor activity in PD-L1-overexpressing mice.

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Tonix Pharmaceuticals Holding Corp.*

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonixs portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonixs CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonixs lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with topline data expected in the fourth quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Enrollment in a Phase 2 study has been completed, and topline results are expected in the third quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), in development for chronic migraine, is currently enrolling with topline data expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets), a once-daily formulation being developed as a treatment for major depressive disorder (MDD), is also currently enrolling with interim data expected in the fourth quarter of 2023. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. Tonixs rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonixs immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second quarter of 2023. Tonixs infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox, for which a Phase 1 study is expected to be initiated in the second half of 2023. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases. The infectious disease portfolio also includes TNX-3900 and TNX-4000, classes of broad-spectrum small molecule oral antivirals.

*All of Tonixs product candidates are investigational new drugs or biologics and have not been approved for any indication.1Dubeykovskaya ZA et al, Nat Commun 20162Kim W et al, Gastroenterology 2021

This press release and further information about Tonix can be found at http://www.tonixpharma.com.

Forward Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as anticipate, believe, forecast, estimate, expect, and intend, among others. These forward-looking statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the SEC) on March 13, 2023, and periodic reports filed with the SEC on or after the date thereof. All of Tonix's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

Jessica Morris (corporate)Tonix Pharmaceuticalsinvestor.relations@tonixpharma.com(862) 904-8182

Maddie Stabinski (media)Russo Partnersmadeline.stabinski@russopartnersllc.com (212) 845-4273

Peter Vozzo (investors)ICR Westwickepeter.vozzo@westwicke.com(443) 213-0505

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