June 27, 2017 Just a few days old embryonic cell clusters: with functional Pramel7 (left), without the protein (right) the development of the stem cells remains stuck and the embyos die. Credit: Paolo Cinelli, USZ

Researchers from the University of Zurich and the University Hospital Zurich have discovered the protein that enables natural embryonic stem cells to form all body cells. In the case of embryonic stem cells maintained in cell cultures, this allrounder potential is limited. Scientists want to use this knowledge to treat large bone fractures with stem cells.

Stem cells are considered biological allrounders because they have the potential to develop into the various body cell types. For the majority of stem cells, however, this designation is too far-reaching. Adult stem cells, for example, can replace cells in their own tissue in case of injury, but a fat stem cell will never generate a nerve or liver cell. Scientists therefore distinguish between multipotent adult stem cells and the actual allrounders - the pluripotent embryonic stem cells.

Epigenetic marks determine potential for development

Differences exist even among the true allrounders, however. Embryonic stem cells that grow in laboratory cell cultures are in a different state than the pluripotent cells found inside the embryos in the first days of development. In a study in the journal Nature Cell Biology, researchers led by Paolo Cinelli of the University Hospital Zurich and Raffaella Santoro of the University of Zurich have now demonstrated the mechanism by which natural allrounders differ from embryonic stem cells in cultures.

At the center of their discovery is a protein called Pramel7 (for "preferentially expressed antigen in melanoma"-like 7) found in the cells of embryonic cell clusters that are just a few days old. This protein guarantees that the genetic material is freed from epigenetic marks consisting of chemical DNA tags in the form of methyl groups. "The more methyl groups are removed, the more open the Book of Life becomes," Cinelli says. Since any cell of the human body can develop from an embryonic stem cell, all genes have to be freely accessible at the beginning. The more a cell develops or differentiates, the stronger its genetic material is methylated and "sealed closed" again. In a bone cell, for example, only those genes are active that the cell requires for its function, the biochemist explains.

Protein is responsible for perfect pluripotency

Despite its short action period of just a few days, Pramel7 seems to play a vital role: When the researchers headed up by Cinelli and Santoro switched off the gene for this protein using genetic tricks, development remained stuck in the embryonic cell cluster stage. In the cultivated stem cells, on the other hand, Pramel7 is rarely found. This circumstance could also explain why the genetic material of these cells contains more methyl groups than that of natural embryonic cells - the perfect allrounders, as Cinelli calls them.

Using the stem cell function to regenerate bone tissue

His interest in stem cells lies in the hope of one day being able to help people with complex bone fractures. "Bones are great at regenerating and they are the only tissue that does not build scars," Paolo Cinelli says. The bone stumps must be touching, however, in order to grow together. When a bone breaks in multiple places and even through the skin, for example, in a motorcycle accident, the sections of bone in between are often no longer usable. For such cases, a bone replacement is required. His team is studying carrier materials that they want to populate with the body's own stem cells in the future. "For this reason, we have to know how stem cells work," Cinelli adds.

Explore further: New tools to study the origin of embryonic stem cells

More information: Urs Graf et al, Pramel7 mediates ground-state pluripotency through proteasomalepigenetic combined pathways, Nature Cell Biology (2017). DOI: 10.1038/ncb3554

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Important pieces of the puzzle to understand what drives diseases such as Alzheimer's and Parkinson's are still missing today. One crucial obstacle for researchers is that it is impossible to examine a living brain cell in someone who is affected by the disease. With the help of a new method for cell conversion, researchers at Lund University in Sweden have found a way to produce diseased, aging brain cells on a large scale in a cell culture dish.

After performing a biopsy on the patient, the skin cells are transformed into brain cells that effectively imitate the disease and the age of the patient. The fact that the cells can now be produced in large quantities enables researchers to carry out a series of experiments that were previously not possible.

A few years ago, Malin Parmar's research team was one of the first in the world to convert human skin cells directly into brain cells without passing the stem cell state. The discovery shocked the researchers and was perceived as almost impossible. The team is now approaching a point where the discovery is about to bear fruit on a wide scale. By following a new method that involves slightly changing the genetic code that triggers cell conversion, the researchers were able to multiply the production of disease-specific brain cells.

"Primarily, we inhibited a protein, REST, involved in establishing identity in cells that are not nerve cells. After limiting this protein's impact in the cells during the conversion process, we've seen completely different results. Since then, we've been playing around with changing the dosage of the other components in the previous method, which also proved effective. Overall, the efficiency is remarkable. We can now generate almost unlimited amounts of neurons from one skin biopsy", says Malin Parmar, professor of developmental and regenerative neurobiology at Lund University.

The increase in production will have far-reaching effects. The new volumes enable research projects that were simply not viable before. Among other things, it opens up research areas linked to new drug testing, the establishment of more accurate disease models and the development of diagnostics to detect the diseases at an earlier stage.

The new cells are not only able to imitate the disease but also the patient's age. By studying the cell in the culture dish, the researchers can now monitor the mechanisms of the disease in an "old" brain cell over time. Neurodegenerative diseases are commonly referred to as "aging brain diseases" and in order to understand them, we must better appreciate how the age specifically affects the course of the disease. The Lund researchers' discovery can hopefully contribute a crucial piece to the puzzle with regard to the connection between the onset of disease and cell aging, something which previous research based on animal experiments and stem cells has failed to provide.

"This takes us one step closer to reality, as we can now look inside the human neurons and see what goes on inside the cell in these diseases. If all goes well, this could fundamentally change the field of research, as it helps us better understand the real mechanisms of the disease. We believe that many laboratories around the world would like to start testing on these cells to get closer to the diseases", says Johan Jakobsson, leader of the molecular neurogenetics research group at Lund University.

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Large-scale Production of Living Brain Cells Enables Entirely New Research - Laboratory Equipment

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The times, they are a-changing.

Since Gregor Mendel unwittingly became the father of genetics by writing down his botanical observations, we have been progressing along swimmingly in our understanding and application of biology.

In the past few years, we ourselves have made some measured leaps forward in the field of biotechnology, some small someless so. Yet with the monumental achievements we have made thus-far from the advent of vaccines to our understanding of how our bodies age and degenerate, we have yet to make that quantum leap forward. That quantum leap may itself not be that far off and if anything is a good indicator of that its observable in the nature of the biotech we are currently developing.

With any huge leap forward, however, come new challenges and a slew of new questions that desperately need to be answered.

This next step in our journey isnt quite like when we eradicated major diseases or began transplanting organs because it isnt about extending human life a mere few additional years. We are taking about a doubling in the years a human may live. Thats right, double.

Now, before you write this off as sci-fi or wishful thinking, let me walk you through exactly what breakthroughs are currently occurring. It all has to do with CRISPR gene-line editing and 3-dimensional printing.

We are at the point where we can take normal somatic cells like the ones from your skin, coax them back into stem cells then re-engineer them into just about any type of cells we want. This means shortly we will be able to take skin cells and make them into heart tissue, or liver, or pancreatic or any number of different ones.

Next, the advances in 3-dimensional printing may shortly be able to take your newly minted cells and print them onto a blank scaffolding in the shape of just about any organ you may need.

Think of that: if you need a new heart it could be as simple as scratching some skin from your arm, reprogramming the cells and then printing you a whole new organ. Not a transplant from a donor, your own cells. This means no rejection and no waitlists. When an organ fails we replace it, again and again and again.

What is to become of a human race that is capable of living seemingly without end? This brings up some serious questions that would have to be answered quickly.

For starters, we see that the current population growth of our species is unsupportable as we resist green energies and advanced farming methods. If humans were to begin to live twice as long or longer we must figure out what we are going to do.

Now the radicals would suggest we simply control the populations but I dont believe that is necessary or even morally right. All we must do is increase our carrying capacity. I must admit that was not my own musing but one my father suggested to me.

If we are able to increase how much food and energy we produce without damaging the planet there is virtually no limit to how many humans can live at once. But the question is, will we resist it as we are now? Will the prospect of living healthily well over a century spur us to begin to accept scientific consensus? Or will we continue down our current path of selfishness and greed? Only time will tell.

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Is doubling our life span desirable? - Price Sun Advocate

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There may be new hope for those suffering from a fatal brain disorder called Huntingtons Disease. Recent research at Emory University, using a groundbreaking gene editing tool called CRISPR-Cas9, has provided new insight into how the disease works, and possible ways to reverse its cruelest effects.

Huntingtons Disease is a genetically inherited condition that leads to nerve cell destruction in the brain. Symptoms, which usually appear in mid-life, include uncontrolled muscle movement, balance issues, mood swings and cognitive decline. Though rates and recording vary from country to country, approximately 30,000 in the U.S. currently suffer from the disease.

While there is no known cure for Huntingtons, a recent study by Chinese scientists at Emory University in Atlanta, Georgia is showing promise. Early results suggest possible treatments for the disease and a path to preventing its occurrence in the first place.

The research is part of an ongoing medical collaboration between the U.S. National Institute of Health (NIH) and the National Natural Science Foundation of China. Under this program, both the U.S. and China contribute funds and scientists for research in both countries.

Emory School of Medicine

Using the revolutionary gene editing technique known as CRISPR-Cas9, researchers at Emory were able to reverse the effects of Huntingtons in test mice.The mice had been genetically modified to carry a human version of the hungtingtin gene that causes the disease. While considered essential for nervous system development in early life, a mutated huntingtin gene can also produce toxic proteins that cause neural generation.

After nine months, when the mice developed the animal version of Huntingtons Disease, researchers used CRISPR-Cas9 to replace the mutant gene with a normal one and then reintroduce the repaired DNA into mice.

Weeks after treatment, the brain-damaging proteins had almost disappeared and motor functions of the mice dramatically improvedthough not to the same level in healthy control mice in which Huntingtons hadnt been induced.

While the results show promise for future human trials involving humans, clinical trials remain a long way off. The long term effectiveness and safety of CRISPR-Cas9 is still under review.

The studys senior author Dr. Xiao-Jiang Li, PhD is optimistic. The findings open up an avenue for treating Huntingtons as well as other inherited neurodegenerative diseases, although more testing of safety and long-term effects is needed, said Xiao-Jiang.

In addition to developing a treatment for victims of Huntingtons, the Sino-U.S. research group hopes to develop ways to reduce the risk for people who are genetically predisposed to developing Huntingtons.

Last year, the same group of Emory researchers had shown they could delete the huntingtin gene in mice older than four months without any known adverse effects. Younger mice without this gene developed fatal pancreatitis. The findings suggest it may someday be possible to safely shut off the gene in adult humans, as well.

Full results of the groups research was published June 19, 2017 in the Journal of Clinical Investigation.

MORE ON CRISPR:

For the second time in a year, doctors in China have used the CRISPR-Cas9 gene editing technique for the treatment of cancer. It is also only the second time CRISPR-Cas9 has been used in human tria

CRISPR-Cas9 is a recently developed gene editing technique that has received worldwide attention because of its relative technical simplicity and wide applications. It is being used in research throughout the world in areas including agriculture, creating new and effective drugs, as well as treating a wide array of genetic disorders.

Defective genes can cause disease. Researchers can use CRISPR Cas-9 like a surgeon uses a scalpelslicing out bad DNA from a damaged genome. Molecular biologists can also transplant normal genes into cellsreplacing damaged or mutated DNA with a new sequence assembled in a lab.

A visualization from the McGovern Institute at MIT explains the science and approach of CRISPR-Cas9.

As the technology advances, scientists hope to someday use CRISPR-Cas9 to create gene therapies that can prevent other inherited diseases, including sickle-cell anemia, Parkinsons disease and cancers that appear to have a genetic component like colon cancer.

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CRISPR gene-editing reverses Huntington's Disease in mice - CGTN America (blog)

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Philadelphia Business Journal

Spark Therapeutics CEO talks drug pricing, gene therapy & his Philadelphia roots Philadelphia Business Journal Spark Therapeutics CEO talks drug pricing, gene therapy & his Philadelphia roots. Jun 27, 2017, 2:23pm EDT. Industries & Tags: Health Care ... Exclusive Online Tools. Research the 3+ year digital archive, and People on the Move leads database download. Cell, gene therapies are hot. But can this startup make them safer?San Francisco Business Times all 181 news articles »

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by Arik Lifschitz on June 28, 2017 12:10 am

Firestone Medal

A recent ceremony honored 33 prize winners representing 26 departments from the three Stanford schools with undergraduate programs Humanities and Sciences; Engineering; and Earth, Energy & Environmental Sciences.

Harry Elam, senior vice provost for education, hosted the June 17 event for the class of 2017 recipients of the Firestone and Robert M. Golden medals and the David M. Kennedy Honors Thesis prizes.

The Firestone and Golden medals are awarded to the top 10 percent of theses completed in a given year. The Firestone Medal for Excellence in Undergraduate Research recognizes theses written in the social sciences, natural sciences, and engineering and applied sciences. The Golden Medal for Excellence in Humanities and Creative Arts similarly distinguishes theses in the humanities or creative projects in the fine arts. The medalists each received an engraved bronze medal, a citation and a monetary award.

The Kennedy Prize is awarded annually to the single best thesis in each of the four areas of humanities, social sciences, natural sciences, and engineering. Recipients of this award have accomplished significantly advanced research in the field and have shown strong potential for publication in peer-reviewed scholarly works. The prize was established in 2008 in recognition of history Professor David M. Kennedys long-standing mentoring of undergraduate writers and his retirement from active teaching. Winners each received an engraved plaque and a monetary award.

The 2017 Kennedy Prizes were presented by Sarah Church, senior associate vice provost for undergraduate education.

The projects conducted by the winners capture the breadth of the undergraduate experience at Stanford. They included research on such topics as gene therapy and protein engineering, computer science education, efficient matching algorithms, the history of national security and the authors of American romanticism. Other winners wrote and directed plays, crafted exceptional poems and excelled as flutists.

The awardees, their thesis titles, honors program or department, and advisers are as follows:

The David M. Kennedy Honors Thesis Prizes

Natural Sciences: Ryan Badiee, Engineering Bidirectional Regulation of Endogenous Genes, Biology, advised by Michael Lin (Neurobiology).

Engineering & Applied Sciences: Griffin Dietz, Childrens Use of Decomposition in Problem Solving as an Early Introduction to Computer Science, Computer Science, advised by James Landay (Computer Science) and Hyowon Gweon (Psychology).

Social Sciences: Whitney McIntosh, France and the Internationalization of Security: A Conceptual History of Security during the Interwar Years (1919-1933), Center on Democracy, Development, and the Rule of Law (CDDRL), advised by Stephen Stedman (CDDRL).

Humanities: Alex Torres, The Blakean Imagination in Nineteenth-Century America: Emerson, Whitman, Dickinson, English, advised by Denise Gigante (English) and Ramn Saldvar (English).

The Firestone Medal for Excellence in Undergraduate Research

Iliana Erteza Bray, Frequency Shifts and Depth Dependence of Beta Band Activity in Rhesus Premotor Cortex Perceptual Decision-Making, Electrical Engineering, advised by Krishna Shenoy (Electrical Engineering).

Marly Carlisle, We Do The Best We Can: Implementation of the McKinney-Vento Act by San Francisco Unified Social Workers, Education, advised by Jelena Obradovic (Graduate School of Education).

Maria Castro, Quantitative Analysis of White Matter Differences in Children Born Preterm and Full Term, Human Biology, advised by Heidi Feldman (Pediatrics Neonatology) and Jeffrey Wine (Psychology).

Melissa Eidman, Still Reservations: Identifying Contributors to Health on the Yurok Reservation, Human Biology, advised by Donald Barr (General Pediatrics), Gabriel Garcia (Gastroenterology and Hepatology), and Sawar Young-Tripp (California Rural Indian Health Board).

Bora Erden, Choice-Predictive Activity in the Macaque Premotor and Motor Cortex, Symbolic Systems, advised by William Newsome (Neurobiology) and James McClelland (Psychology).

Kathryn Evans, Using Viral Tools to Dissect Neural Circuits: Exploring the Nigrostriatal and Claustrocingulate Pathways in Mice, Biology, advised by Karl Deisseroth (Bioengineering).

Andrea Fisher, Genomic Analysis of Southeast Asian and Sahul Ancestry, Biology, advised by Marcus Feldman (Biology) and Richard Klein (Biology).

Zi Yang Kang, Strategy-Proof Bilateral Trade, Mathematics, advised by Jan Vondrak (Mathematics).

Sophia Laurenzi, The Gray Matter of Young Adulthood: Neuroscience, Social Trends, and Justice Reform, Science, Technology, and Society (STS), advised by Angela Garcia (Anthropology).

Lauren Newby, From Zero to Sixty: Explaining the Proliferation of Shia Militias in Iraq after 2003, Center for International Security & Cooperation (CISAC), advised by Martha Crenshaw (CISAC).

Nghia Nguyen, A Behavioral System for Imaging Prefrontal Cortex Activity in Freely Behaving Mice, Biomechanical Engineering, advised by Liqun Luo (Biology) and Ovijit Chaudhuri (Mechanical Engineering).

Brett Parker, Election or Appointment? A Quantitative Study of the Effects of Judicial Selection Method on Judicial Voting in Criminal Procedure Cases, Political Science, advised by David Brady (Political Science).

Indira Puri, On the Probability of Receiving a Top Choice Match, Economics, advised by Jonathan Levin (Economics and Graduate School of Business).

Daniel Sanchez-Ordonez, International Monetary Policy Spillover in Colombia: An SVAR Analysis, Economics, advised by John Taylor (Economics).

Lydia Tam, Identifying the Cellular Origin and Enzymatic Mechanism of Activity-regulated Neuroligin-3 Secretion, Biology, advised by Michelle Monje-Deisseroth (Neurology).

Eileen Williams, Interhemispheric Amygdala Connectivity Across Puberty and its Relation to Depressive Symptomatology, Psychology, advised by Ian Gotlib (Psychology).

Ethan Williams, Sycamore Knoll: A Wave-Planed Pop-up Structure in a Sinistral-oblique Thrust System, Southern California Continental Borderland, Geophysics, advised by Simon Klemperer (Geophysics).

Cristian Zanoci, Entanglement and Transport Properties of Non-Equilibrium Steady States of 1-D Quantum Systems, Physics, advised by Patrick Hayden (Physics) and Brian Swingle (UMD Physics).

Yuan Zhang, Bioactive Lipids Enhance Cardiomyocyte Differentiation from Human Induced Pluripotent Stem Cells, Biology, advised by Sean Wu (Medicine).

The Robert M. Golden Medal for Excellence in the Humanities and Creative Arts

Surabhi Balachander, Our Color in the Fields: Exploring the Intersections of Agriculture and Race in American Literature, Comparative Studies in Race and Ethnicity (CSRE), advised by Michele Elam (English) and Solmaz Sharif (English).

Madelaine Bixler, Writer/Director: In Volution, Theater and Performance Studies (TAPS), advised by Leslie Hill (TAPS) and Cherrie Moraga (TAPS).

Talia Charme-Zane, Freaky Forests, Gay Princes, and Guilty Children: A Queer Reading of Sondheims Into The Woods, Feminist, Gender, and Sexuality Studies, advised by Sianne Ngai (English).

Joshua De Leon, This Brown Body is a Vessel, Arts Institute, advised by Michele Elam (English), Solmaz Sharif (English), and Whitney Lynn (HIA).

Michael Gioia, The Revolutionary Priest: An Intellectual Biography of Claude Fauchet, History, advised by Keith Baker (History) and Dan Edelstein (French and Italian).

Gabriella Johnson, Re-Reading the Mulatta: A Black Feminist Approach to Understanding the Mulatta in 21st Century Literary Production, African and African American Studies, advised by Michele Elam (English) and Alvan Ikoku (Comparative Literature).

Jacqueline Langelier, Photography, Art and Art History, advised by Gail Wight (Art & Art History).

Quyen Nguyen, Danh V: Ghost Work, Art and Art History, advised by Alexander Nemerov (Art & Art History).

May Peterson, Venantius Fortunatus as Auctor of the Sacred: From Material to Ethereal in Sixth-Century Gaul, Classics, advised by Grant Parker (Classics) and Bissera Pentcheva (Art & Art History).

Al Yuen, Flute Performance, Music, advised by Alexandra Hawley (Music).

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2017 Firestone and Golden medal, Kennedy Thesis Prize recipients honored - Stanford University News

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Thirty-six percent of Hispanic families in the U.S. with a common form of retinitis pigmentosa got the disease because they carry a mutation of the arrestin-1 gene, according to a new study from researchers at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health.

Retinitis pigmentosa is a group of rare, genetic eye disorders in which the retina of the eye slowly degenerates. The disease causes night blindness and progressive loss of peripheral vision, sometimes leading to complete blindness. According to Stephen P. Daiger, Ph.D., senior author of the study, an estimated 300,000 people in the U.S. suffer from the disease, which gets passed down through families.

In the study published recently in Investigative Ophthalmology & Visual Science, UTHealth researchers found that in a U.S. cohort of 300 families with retinitis pigmentosa, 3 percent exhibited a mutation of the arrestin-1 gene. However, more than 36 percent of Hispanic families from the cohort exhibited the arestin-1 mutation and they all came from areas in the Southwestern U.S., such as Texas, Arizona and Southern California.

When I started studying retinitis pigmentosa in 1985, we set out to find the one gene that causes the disease. Thirty-three years later, weve found that more than 70 genes are linked to retinitis pigmentosa, said Daiger, a professor in the Human Genetics Center and holder of the Thomas Stull Matney, Ph.D. Professorship in Environmental and Genetic Sciences at UTHealth School of Public Health.

Some of the genes that cause retinitis pigmentosa are recessive, which means two mutations are required, and some are dominant, which means you only need one mutation. Arrestin-1 piqued Daigers interest because that particular mutation is dominant while all previously found mutations in the gene are recessive. This unexpected finding shows that even a single mutation in the gene is sufficient to cause the disease.

Daiger and his team have identified the genetic cause of retinitis pigmentosa for 75 percent of families in their cohort. Possible treatments for some forms of retinitis pigmentosa are being tested but are still limited. However, the speed at which companies are developing gene therapies and small molecule therapies gives reason to hope, he said. Daiger and his collaborators have begun to connect some of the patients in the retinitis pigmentosa cohort to clinical trials that treat specific genes.

I want our cohort families to know that even if there is not an immediate cure for their specific gene mutation, at this rate it wont be long until a therapy becomes available, said Daiger, who also holds the Mary Farish Johnston Distinguished Chair in Ophthalmology at McGovern Medical School at UTHealth.

UTHealth coauthors include Lori S. Sullivan, Ph.D.; Sara J. Browne, Ph.D.; Elizabeth L. Cadena; Richard S. Ruiz, M.D., and Hope Northrup, M.D. Additional co-authors are from Nationwide Childrens Hospital; Kellogg Eye Center at the University of Michigan; Retina Foundation of the Southwest; Casey Eye Institute at Oregon Health and Science University; Vanderbilt University and the Department of Molecular and Human Genetics at Baylor College of Medicine.

Support for the study, titled A novel dominant mutation in SAG, the arrestin-1 gene, is a common cause of retinitis pigmentosa in Hispanic families in the Southwestern United States, was provided by the William Stamps Farish Fund and the Hermann Eye Fund.

Additional support was provided by the National Institutes of Health (EY007142, EY009076, EY011500, EY010572 and K08-EY026650), a Wynn-Gund TRAP Award, the Foundation Fighting Blindness, the Max and Minnie Voelker Foundation and a grant to the Casey Eye Institute from Research to Prevent Blindness.

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Gene Mutation Linked to Retinitis Pigmentosa in Southwestern US Hispanic Families - Texas Medical Center (press release)

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Fort Worth Star Telegram (blog)

It's time for baseball to allow the use of PEDs Fort Worth Star Telegram (blog) A former Major League Baseball trainer is fairly certain that ballplayers are using steroids again. That's if they ever really stopped, the trainer, who worked for more than 10 seasons with a big league ballclub, recently told me. It wouldn't ...

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It's time for baseball to allow the use of PEDs - Fort Worth Star Telegram (blog)

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Mohammad Alyamani, Ph.D., with lab technician Yoon-Mi Chung. Credit: Cleveland Clinic

Cleveland Clinic researchers have shown for the first time how a class of advanced prostate cancer drugs are processed in the body and how their anti-tumor activity might change depending on how they are metabolized. Their pre-clinical findings, just published in Cell Chemical Biology, may lay the foundation for improving therapies for treatment-resistant, aggressive prostate cancer.

Next-generation anti-androgens are potent drugs that work by cutting off the prostate tumors supply of androgens (male hormones), which fuel prostate cancer. The drugs, used in patients whose cancer has become resistant to hormone deprivation therapy, have been shown to improve survival in men with metastatic disease. Unfortunately, prostate tumors eventually become resistant to these drugs, highlighting the need for new therapies.

Despite an array of improved treatment options that have become available over the past decade, prostate cancer remains the second leading cause of cancer mortality in men in the United States. There are few therapeutic options for men whose cancer has become resistant to all therapies, said Nima Sharifi, M.D., lead author on the study. Our goal is to improve the use and role of these existing drugs and hopefully design new therapies that work better and longer.

Galeterone is a steroidal anti-androgen that was recently studied in a clinical trial. Dr. Sharifis team in the Cleveland Clinic Lerner Research Institutes Department of Cancer Biology has shown that when galeterone is metabolized, it is converted to the intermediate molecule D4G, which blocks androgen synthesis and reduces the amount of androgens available to cancer cells. A pitfall is that galeterone is also converted to another molecule that may stimulate the tumor.

Dr. Sharifi previously found that another steroidal anti-androgen drug, abiraterone, is metabolized in a similar manner. He went on to show in landmark studies that abiraterones metabolite D4A has greater anti-tumor activity than abiraterone alone and that other molecules stimulate tumor growth, suggesting that the drug should be fine-tuned to improve efficacy.

Dr. Sharifis new findings suggest that effective steroidal anti-androgens share common metabolic activities and that their metabolites should be closely examined for their effects on tumor survival. The findings may also guide medical decision making in the use of steroidal vs. nonsteroidal drugs for advanced prostate cancer.

New agents and a clearer understanding of drug mechanisms are both urgently required to improve outcomes for treatment-resistant advanced prostate cancer, said Dr. Sharifi. This work provides an important foundation that hopefully will lead to better treatment strategies for this disease.

This article has been republished frommaterialsprovided by Cleveland Clinic. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Alyamani, M., Li, Z., Berk, M., Li, J., Tang, J., Upadhyay, S., . . . Sharifi, N. (2017). Steroidogenic Metabolism of Galeterone Reveals a Diversity of Biochemical Activities. Cell Chemical Biology. doi:10.1016/j.chembiol.2017.05.020

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Advanced Cancer Drug Study Highlights Need for Novel Approaches - Technology Networks

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Using hormones to treat transgender children who feel that they are members of the opposite sex, which is becoming commonplace in medicine, could have serious long-term effects on children, doctors are warning in a new report.

In a paper published in the journal The New Atlantis this week, Paul Hruz of the Washington University Medical School and Lawrence Mayer and Paul McHugh of Johns Hopkins Medical School say such treatments could have serious health implications, the New York Post reports.

The paper, called Growing Pains: Problems with Puberty Suppression in Treating Gender Dysphoria, notes a recent analysis by UCLA found that about 1.4 million people in the United States identify as transgender, a growing number of whom are children.

The number of children diagnosed with gender dysphoria described by clinicians as incongruence between ones experienced/expressed gender and assigned gender has been on the rise.

A gender identity clinic for children in the United Kingdom, for instance, reported a 2,000 percent increase in referrals since 2009, with those for children under the age of 6 going from six to 32 in the same time period.

Well-meaning parents have been increasingly trying hormone suppression, which prevents sex organs in boys and girls from developing in the usual way, Hruz, Mayer, and McHugh note.

While that may allow children to postpone decisions about actual sex-reassignment surgery, the authors argue that this therapy may have real and long-term effects on childrens physical and psychological development.

Whether blocking puberty is the best way to treat gender dysphoria remains far from settled, they write, and it should be considered ... a drastic and experimental measure.

2017 NewsmaxHealth. All rights reserved.

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Gosselies, Belgium,26 June 2017; 7am CEST BONE THERAPEUTICS (Euronext Brussels and Paris: BOTHE), the bone cell therapy company addressing high unmet medical needs in orthopaedics and bone diseases, today announces that the European Patent Office (EPO) has notified the Company of its intention to grant a key patent covering its first-in-class allogeneic cell therapy technology.

Once granted, the patent titled, Osteogenic differentiation of bone marrow stem cells and mesenchymal stem cells using a combination of growth factors, will provide legal protection to Bone Therapeutics both for the manufacturing methods and for the distinct cell type used in its allogeneic cell therapy technology. Specifically, the patent covers methods to manufacture differentiated and biologically active osteoblastic (bone-forming) cells from bone marrow stem cells, using a specific combination of growth factors, and also covers a new class of osteoblastic cells suitable for allogeneic administration to the patient.

Bone Therapeutics will now validate the patent in several countries in the European Union, potentially allowing IP protection for its allogeneic bone cell therapy platform until 2029. Patents from the same patent family have already been granted in Japan, Australia and Singapore and applications are pending in the USA, Canada, India and South Korea. ALLOB, Bone Therapeutics most advanced allogeneic bone cell therapy product, is currently being evaluated in Phase I/IIA clinical trials for delayed-union fractures and spinal fusion, for which interim results are expected in the third quarter this year.

Thomas Lienard, Chief Executive Officer of Bone Therapeutics, commented: This notice from the European Patent Office confirms our allogeneic bone cell therapy technology is both innovative and distinctive. When granted, this European patent will significantly strengthen our IP position in the field of bone cell therapy, giving us further validation for the scientific and commercial development of our cell therapy products whilst also enhancing our position with respect to new partnerships.

Dr. Miguel Forte, Chief Medical Officer of Bone Therapeutics, further noted: Obtaining this patent is an important step in the development of our allogeneic bone cell therapy technology. It will provide a solid IP protection for our current work and for future technological advances, allowing us to continue our efforts to create patient-centric and commercially interesting bone cell therapy solutions.

About Bone Therapeutics

Bone Therapeutics is a leading cell therapy company addressing high unmet needs in orthopaedics and bone diseases. Based in Gosselies, Belgium, the Company has a broad, diversified portfolio of bone cell therapy products in clinical development across a number of disease areas targeting markets with large unmet medical needs and limited innovation. Our technology is based on a unique, proprietary approach to bone regeneration which turns undifferentiated stem cells into osteoblastic, or bone-forming cells. These cells can be administered via a minimally invasive procedure, avoiding the need for invasive surgery. Our primary clinical focus is ALLOB, an allogeneic off-the-shelf cell therapy product derived from stem cells of healthy donors, which is in Phase II studies for the treatment of delayed-union fractures and spinal fusion. The Company also has an autologous bone cell therapy product, PREOB, obtained from patients own bone marrow and currently in Phase III development for osteonecrosis and non-union fractures.

Bone Therapeutics cell therapy products are manufactured to the highest GMP standards and are protected by a rich IP estate coveringnine patent families. Further information is available at: http://www.bonetherapeutics.com.

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in thispress release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

Josh Sandberg has been an executive search consultant focused exclusively on orthopedic and spine start-ups since 2004. He has had a tremendous impact in helping his clients avoid costly hiring mistakes by his deep industry knowledge and network. In 2010, Josh co-founded Ortho Spine Companies, which is the parent company of Ortho Spine Distributors (OSD), Surg.io and Ortho Sales Partners (OSP). OSD a searchable database that helps ease the frustration of finding orthopedic distributors throughout the country. Surg.io is the ultimate distributor toolkit that offers distributors the tools necessary to build the foundation of a scalable and highly functioning sales organization. OSP is an end-to-end solution that helps companies approach the Global Market in a cost efficient way. Our team has hundreds of years of experience and can help you navigate the many challenges present in bringing new technologies to the market.

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Bone Therapeutics receives Intent to Grant Notice from European Patent Office for allogeneic bone cell therapy platform - OrthoSpineNews

Recommendation and review posted by sam

A Winnipeg toddlerwith acute myeloid leukemia has passed away after hundreds came forward to register as donors in an effort to help him.

After being diagnosed with the disease on Oct. 25, 2016, 20-month-old Tegveer Minhaswasforced to go through two rounds of chemotherapy, losing his hair and a lot of weight.

During that time, his family put out calls to the public to come forward and register bone marrow and stem cell information, in hopes that someone would be a match.

Hundreds of people in Manitoba, Ontario and Alberta were swabbed, and Tegveer was able to receive a stem cell donation, but Minhas said it didn't work.

"After 8 months of struggle, he passed away on June 18th, early in the morning at 6 a.m.," said his dad,Sukhbir Minhas.

Minhas saidhis family is trying to stay strong, but he admits they are having a hard time.

"He was a happy soul, he loved to go out, we took him to Clear Lake on June 4th, and I wish I knew that he would love it so much, we were planning to go back again," Minhas said.

The hundreds of strangers who registered as donors, prayed for and even phoned the family to offer supportmeant the world to Minhas and his wife, he said.

"There was a time in the hospital, it was in January I think, we were so sure that my son's going to be all right, because it's just not me and my wife, it's thousands of other people who are praying for him," he said.

He urged people, especially young people aged 18 to 35, to register as donors to help other families like his.

"I respect every person from the bottom of my heart who went and got themselves swabbed, and even those who just had a thought of going and get themselves swabbed. That means they care for my son as I and my wife," he said.

"It feels a little better than if there was nobody for us."

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'He was a fighter' says father after toddler dies of leukemia - CBC.ca

Recommendation and review posted by Bethany Smith

If youve ever been concerned about hair loss in the past, this could be your lucky day. A new experiment carried out by Michael Rosenblum, assistant professor of dermatology at the University of California has proved just how useful regulatory T cells (tregs) are when it comes to hair loss. Previously scientists were led to believe that these cells single task was to inform other cells when to attack. However, what Rosenblum discovered when he shaved the mouse he was experimenting on, he noticed that the hair never grew back.

From the study, Rosenblum and team discovered that tregs in the skin had high levels of Jagged 1 (Jag1) which has the duty of calling in the stem cells through a process called Notch signaling. Removing the tregs reduced the notch signaling and when Jag1 was added the stem cells were called which then activated the process of follicle regeneration.

This study will be of particular interest to one type of hair loss sufferer: those with alopecia areata. This is an autoimmune disease that impedes hair follicle regeneration and affects as many as 1.7 percents of the U.S. population. Until now, very little has been known about what causes hair loss, but this research will give doctors and scientists everywhere new direction and a potential cure.

As well as hair regeneration, this process could be used to correct other skin related problems such as wound repair. What we found here is that stem cells, and immune cells have to work together to make regeneration possible, says Rosenblum. So dont despair if youre losing your hair, help is on the way!

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Say Goodbye to Hair Loss and Hello to Body Regeneration - TrendinTech

Recommendation and review posted by simmons

Jennifer Doudna remembers a moment when she realized how important CRIPSRthe gene-editing technique that she co-discoveredwas going to be. It was in 2014, and a Silicon Valley entrepreneur had contacted Sam Sternberg, a biochemist who was then working in Doudnas lab. Sternberg met with the entrepreneur in a Berkeley cafe, and she told him, with what he later described to Doudna as a very bright look in her eye that was also a little scary, that she wanted to start applying CRISPR to humans. She wanted to be the mother of the first baby whose genome had been edited with the technique. And she wanted to establish a business that would offer a menu of such edits to parents.

Nothing of the kind could currently happen in the U.S., where editing the genomes of human embryos is still verboten. But the entrepreneur apparently had connections that would allow her to offer such services in other countries. Thats a true story, Doudna told a crowd at the Aspen Ideas Festival, which is co-hosted by the Aspen Institute and The Atlantic. That blew my mind. It was a heads-up that people were already thinking about thisthat at some point, someone might announce that they had the first CRISPR baby.

The possibility had always been there. Bacteria have been using CRISPR for billions of years to slice apart the genetic material of viruses that invade their cells. In 2012, Doudna and others showed how this system could be used to deliberately engineer the genomes of bacteria, cutting their DNA with exceptional precision. In quick succession, researchers found that they could do the same in mammalian cells, mice, plants, andin early 2014monkeys. I had all of this at the back of my mind, Doudna told me after her panel. But Sternbergs story about his meeting was the moment where I said I needed to get involved in this conversation. Im not going to feel good about myself if I dont talk about it publicly.

That has not been an easy journey. Doudna built her career on molecules and microbes. As few as five years ago, she was, by her own admission, working head-down in an ivory tower, with no plans of milking practical applications from her discoveries, and little engagement with the broader social impact of her work.

But CRISPR forcefully yanked Doudna out of that closeted environment, and dumped her into the midst of intense ethical debates about whether its ever okay to change the DNA of human embryos, whether eradicating mosquitoes is a good idea, and whether fixing the genes behind inherited diseases is a blow to disabled communities. Now, shes a spokesperson for a field, and an influencer of policy. She regularly makes appearances at conferences and panel discussions, which she often shares with not just scientists but also philosophers, ethicists, and policy-makers. With Sternberg, she is the author of a new book called A Crack in Creation, describing her role in the CRISPR story.

All of this work consumes up to half of her time, taking her away from her lab of 25 people. I find myself really struggling to maintain that balance, she says. But those are the cards Ive been dealt and I feel an obligation to being involved in [the debates around CRISPR]. There arent that many people who know the technology deeply and willing to talk publicly about the societal and ethical issues. I have many science colleagues who dont want to get involved. Yet it has to be done.

Her upbringing prepared her well for this newfound role. Her father was a professor of American literature at the University of Hawaii, who was fiercely intellectual and politically conservative but never dogmatic. Her family dinner table was a place where opposing views were shared openly and debated open-mindedly. It still is: Many of Doudnas in-laws staunchly oppose any form of genetic modification, so her work is a point of contention, even among close family. I spend a lot of time talking to people like me, and its a big challenge is to reach out those who arent, she says. Its a paradigm for the challenges in our country right now.

With her increasing slate of talks, many of those unfamiliar opinions now seek her out. After a recent panel, a fellow speaker told her that her sister was born with a rare mutation that left her intellectually disabled and led to her dying in her 20s. I want you to know, the speaker said, that if it were possible to use gene-editing to get rid of that mutation permanently, I would have no hesitation. On the flipside, Doudna was recently interviewed by a journalist whose son has Downs syndrome. I want you to know, the journalist said, that I would never use CRISPR on him because hes perfect just the way he is.

Im very respectful of both those points of view, she tells me. And Ive learned a lot about myself in these last five years.

Much of the rhetoric around CRISPR is overblown. It is unlikely, for example, that CRISPR could ever be used to design babies to be smarter, taller, or free of conditions like obesity or schizophrenia, because such traits are the work of hundreds of genes, each with small effects. The threat of the technique can also be exaggerated in equal measure to its promise. One of Doudnas colleagues recently attended a meeting at the Department of Energy, and was asked by a member of the Trump administration: What about CRISPR? Thats dangerous. We need to get rid of it.

Well you cant, Doudna says plainly. Were in the system were in, and we have to deal with the technology in that context. Ive been encouraging an international discussion because the worst thing we could do is to ignore it, and for scientists not to get involved.

Read more here:

How CRISPR Yanked Jennifer Doudna Out of the Ivory Tower - The Atlantic

Recommendation and review posted by simmons

San Francisco Business Times

Cell, gene therapies are hot. But can this startup make them safer? San Francisco Business Times ... and the CEO of Veneti. Using a cloud-based software platform, San Francisco's Vineti wants to be the FedEx of cell and gene therapies. ... Exclusive Online Tools. Research the 3+ year digital archive, and People on the Move leads database download.

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Cell, gene therapies are hot. But can this startup make them safer? - San Francisco Business Times

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Minneapolis, MN, June 26, 2017 (GLOBE NEWSWIRE) -- BioSig Technologies, Inc.(OTCQB:BSGM), a medical device company developing a proprietary platform designed to address an unmet technology need for the $4+ billion electrophysiology (EP) marketplace, today announced that the American Heart Associations 13thAnnualBasic Cardiovascular Sciences (BCVS) 2017 Scientific Sessions: Pathways to Cardiovascular Therapeuticshas accepted two abstracts for presentation that feature novel preclinical findings with BioSigs PURE EP System. The conference will be held July 10-13 in Portland, Oregon and includes the next best thing in cardiovascular research.

The abstracts, entitled, Use of a Novel Electrogram Filter to Visualize the Conduction Tissue Signals in the Ventricle in Sinus Rhythm and Arrhythmia: Canine Studies and "Assessment of Catheter Position Above or Below the Aortic Valve by Evaluation of Characteristics of the Electrogram: An Acute Canine Study", werewritten in collaboration with electrophysiologists from Mayo Clinic and will be presented during scientific poster sessions from 4:30pm 7pm on July 10 and 12, respectively.

BioSig is extremely pleased to have two abstracts, featuring our PURE EP System, accepted into the Basic Cardiovascular Sciences Conference sponsored by the American Heart Association, stated Mr. Ken Londoner, Chief Executive Officer and Chairman of BioSig Technologies. Our collaboration with Mayo Clinic physicians has resulted in seven publications to date featuring BioSigs platform technology. And, we intend to strive towards improving visualization of cardiac signal information during EP procedures to help bring benefits to those patients who suffer with, and doctors who treat, arrhythmia.

About the Basic Cardiovascular Sciences Conference

The 13th Annual BCVS 2017 Scientific Sessions: Pathways to Cardiovascular Therapeutics has become the premier conference for molecular cardiovascular biology and disease. Sponsored by the American Heart Association Basic Cardiovascular Sciences Council, the worlds leading organization of cardiovascular scientists, this conference strives to improve basic cardiovascular regulation through new therapies and insights in cardiovascular disease, as well as research in fields like microRNAs, cardiac gene and cell therapy, cardiac development, as well as tissue engineering and iPS cells.

BCVS 2017 convenes basic and translational cardiovascular scientists from around the world with the common goal to discover pathways to cardiovascular therapeutics and promoting cardiovascular health. This meeting has become the go to meeting for intra- and interdisciplinary cross-fertilization of ideas and incorporation of new approaches from the general scientific community and plays a pivotal role in the training of junior scientists and trainees. The program includes a diversity of speakers representing the best cardiovascular scientists from around the world.

About BioSig Technologies

BioSig Technologies is a medical device company developing a proprietary technology platform designed to improve the $4+ billion electrophysiology (EP) marketplace ( http://www.biosigtech.com). Led by a proven management team and a veteran, independent Board of Directors, Minneapolis-based BioSig Technologies is preparing to commercialize its PURE EP(TM) System. The technology has been developed to address an unmet need in a large and growing market.

The PURE EP System is a novel cardiac signal acquisition and display system which is engineered to assist electrophysiologists in clinical decision making during procedures to diagnose and treat patients with abnormal heart rates and rhythms. BioSigs main goal is to deliver technology to improve upon catheter ablation treatments for prevalent and deadly arrhythmias. BioSig has partnered with Minnetronix on technology development and is working toward FDA 510(k) clearance and CE Mark for the PURE EP System.

Forward-looking Statements

This press release contains forward-looking statements. Such statements may be preceded by the words intends, may, will, plans, expects, anticipates, projects, predicts, estimates, aims, believes, hopes, potential or similar words. Forward-looking statements are not guarantees of future performance, are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Companys control, and cannot be predicted or quantified

See the article here:
Novel Findings Obtained with the PURE EP System to be Presented at American Heart Association's BCVS Scientific ... - Cardiovascular Business

Recommendation and review posted by Bethany Smith

Queens Tribune

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Intranasal ipratropium in the treatment of vasomotor rhinitis - Queens Tribune

Recommendation and review posted by Bethany Smith

T

he ruckus over the CRISPR gene-editing system hides a dark reality: its high cost may make it unaffordable and questions remain whether most insurance companies will pay for it.

As CRISPR begins to move forward in clinical trials, there are some signals about how it may or may not be received commercially. Other types of gene therapies carry a price tag that is likely to induce sticker shock. If adopted, these therapies will add striking new cost burdens to our health care system.

The cost isnt coming down, said Mark Trusheim, director of the Massachusetts Institute of Technologys NEW Drug Development Paradigms, a think tank working on the problem of how we will pay for expensive new drugs. Companies will say, We are developing these medicines, just pay us; insurers will say, We cant afford it.'

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A few years ago, Dutch drug company uniQure set up a plant in Lexington, Mass., to make a gene therapy called Glybera, at the time the most expensive drug in the world. It used viruses to slip copies of a gene into human cells to restore an enzyme needed to break down fats. The cost? $1.4 million per patient. The company eventually abandoned its bid to bring Glybera to the U.S. and, after having sold it just once in Germany, recently withdrew it from European markets, rendering it a commercial failure.

Spark Therapeutics of Philadelphia is vying to bring the first gene therapy to market in the U.S. to treat a rare genetic eye disease called Leber congenital amaurosis 2. Analysts said it could cost a half-million dollars per eye. Like Glybera, Sparks treatment is a form of traditional gene therapy, which makes use of viruses to get bits of restorative code into our cells.

Do CRISPR enthusiasts have their head in the sand about the safety of gene editing?

CRISPR will allow us to alter our existing genes. But it often relies on using viruses to shuttle the molecular gene-editing systems into our cells, and can be as expensive as other gene therapies.

Editas Medicine plans to use CRISPR-Cas9 to treat various diseases, including Leber congenital amaurosis. Enthusiasm is great for interventions in the eye, New York University bioethicist Arthur Caplan told me. They permit trying one eye at a time and it is easy to tell if anything positive happens. Safety is much easier to ensure. But in its annual report, Editas noted significant uncertainty on whether payers would cover the treatment. In fact, a handful of insurance companies (VantageBlue from Blue Cross Blue Shield of Rhode Island, Select Health, and VIVA Health) have issued policy documents that exclude gene therapy from coverage, a move that experts say establishes policy against paying for CRISPR-based therapeutics.

The Institute for Clinical and Economic Review released a report in March stating there are 12 to 14 gene therapy candidates that are expected to be among the first for commercial approval. With payer budgets already stretched, and reining in the costs high on the agenda, both public and private payers will likely balk at the cost of some of these gene-based treatments, the American Journal of Managed Care wrote in a reflection on the report. Europe has the lead in approved gene therapies, and the first such drug to be approved had a launch price of $1.4 million. Can the US health care system absorb the cumulative impact of such prices, considering that 10 percent of the population has a rare condition linked to a genetic defect?

Five major gene therapy companies went publiclast year, suggesting that investors are ready to bet on the commercial prospects. Editas signed a deal with Juno Therapeutics that could be worth up to $737 million. The companies would combine CRISPR with other tactics to trick the immune systems T cells to fight cancer. Those tactics could include disabling genes in T cells that prevent cancer cells from shutting down a T cell response, and adding bits of genetic code to engineer new receptors into T cells to let them attach to abnormal proteins in cancer cells called neoantigens.

Gene and cell therapies that run into the six figures and beyond are poised to heighten the cost of cancer treatments, which not everyone may be able to afford. In fact, oncologist Dr. Siddhartha Mukherjee, author of the bestselling Emperor of All Maladies, gave a speech this month at the annual American Society of Clinical Oncology meeting that warned about dividing the world into the rich who can afford personalized cancer treatment and the poor who cannot.

Tania Bubela, a law and policy expert, and Chris McCabe, a health economist, both at the University of Alberta, will be holding a workshop in late June in Banff, Canada, to explore how to enable access to high-priced technologies. According to Bubela, gene-editing systems such as CRISPR-Cas9 promise to heighten the tension around health care policy. One idea for easing the tension is for regulators to permit drug makers to get reimbursed from insurers before their gene therapy gets FDA approval, while requiring drug makers to collect more data before charging full price a kind of price control.

Companies will charge whatever the market will bear, Bubela told me. Im not even sure that many of these gene therapies will work, and not all medicine is worth the price. But if these technologies become broadly used, especially in altering T cells for cancer, payers wont meet the demands of steep prices, and Bubela predicts that the system implodes under its own weight.

I believe that part of the problem lies in financial dealings. The Broad Institute, for instance, holds patents to gene editing tools such as CRISPR-Cas9 and CRISPR-Cpf1 and has issued exclusive licenses to Editas to use these tools for medical purposes. It could issue more-affordable CRISPR licenses one gene at a time, say directly to Juno Therapeutics, which now accesses them through its multimillion dollar deals with Editas. But that would cut Editas investors out of the loop. Such deals tend to inflate drug prices, since venture and public investors in Editas demand a cut on each CRISPR application. As investors engage in layers of transactional deals along the top of the food chain, the costs of gene therapies go up while the financiers may shift blame for a lack of patient coverage to insurance companies.

Dr. Stuart Orkin, a pediatric oncologist at Boston Childrens Center, and Dr. Philip Reilly, a partner at Third Rock Ventures, an Editas funder, coauthored a paper in Science magazine saying that sticker shock shouldnt halt commercialization. It can cost $300,000 a year to treat a single hemophilia patient with existing standard treatments and $25,000 to treat a single sickle-cell patient. Given costs like those, one-time gene therapy treatments running into the six figures may be comparatively affordable if an insurer makes payments to a drug-maker over a decade that are tied to the drugs continued performance. In fact, the idea of spreading payments over years as annuities originated with corporate-friendly FDA commissioner Scott Gottlieb in a 2014 paper he co-authored for the American Enterprise Institute.

Other performance-based models are being tested. GlaxoSmithKline, for example, is trying to bring a $665,000 gene therapy to the U.S. to treat an immune system disorder. The company said it will tie the cost of the drug to its performance in patients with a money-back guarantee. The reality is its very tough, and it doesnt come easy, said Jonathan Appleby, a chief scientific officer for the companys rare disease unit.

Broad Institute prevails in heated dispute over CRISPR patents

Orkin and Reilly also like the idea of using U.S. government funds from the Orphan Drug Act, established in 1983, to pay gene therapy companies for their commercial products. Another idea for keeping gene therapy, including CRISPR-based therapies, affordable is that investors could ask insurance companies to buy in bulk. MITs Ernst Berndt, inspired in part by volume purchases of vaccines in Africa, has proposed advanced market commitments through which insurance groups commit to buying a bunch of expensive drugs. That model that could be applied to gene therapies, but the insurers may not go for it without a bit more give.

In 2009, the Biologics Price Competition and Innovation Act created a pathway for approving generic biologics, also known as biosimilars. It may apply to CRISPR-based biosimilars, but generic gene-editing and thus competition to drive down prices is unlikely to appear for decades. Cathryn Donaldson, a spokesperson for Americans Health Insurance Plans, noted that a lack of generic forms of CRISPR means drug makers may charge whatever they want for their branded medication.

In 1968, Garrett Hardin argued in his now-classic essay, The Tragedy of the Commons, that a shared-resource system will tend to be depleted by self-interested individuals. He also argued against exponential growth to which we could add today the growth of biotech valuation.

Health care is a limited shared resource, and expensive new technologies could add pressures resulting in unequal access, especially to cancer therapies. Given the aggressive drive for money, and without new approaches in thinking, we are headed for disaster. One of two things will happen: either we will embrace a national health care system with broad access but that severely limits expensive new drugs, gene therapies, and CRISPR-based biologics; or these treatments will be available to only the wealthiest among us who can pay for them, a dystopian vision which is perverse but perhaps more realistic considering the pressures for a return on investment.

Writer Jim Kozubek is the author of Modern Prometheus: Editing the Human Genome with Crispr-Cas9, published by the Cambridge University Press.

Jim Kozubek can be reached at jimkozubek@gmail.com

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Who will pay for CRISPR? - STAT News - STAT

Recommendation and review posted by Bethany Smith

On the eve of publishing her new book, Jennifer Doudna, a pioneer in the field of CRISPR-Cas9 biology and genome engineering, spoke with Fast Company about the potential for this new technology to be used for good or evil.

The worst thing that could happen would be for [CRISPR] technology to be speeding ahead in laboratories, Doudna tells Fast Company. Meanwhile, people are unaware of the impact thats coming down the road. Thats why Doudna and her colleagues have been raising awareness of the following issues.

Related:CRISPR Pioneer Jennifer Doudna On Gene Editings Potential For Good And Evil

Editing sperm cells or eggsknown as germline manipulationwould introduce inheritable genetic changes at inception. This could be used to eliminate genetic diseases, but it could also be a way to ensure that your offspring have blue eyes, say, and a high IQ. As a result, several scientific organizations and the National Institutes of Health have called for a moratorium on such experimentation. But, writes Doudna, its almost certain that germline editing will eventually be safe enough to use in the clinic.

Using a CRISPR-related technique known as gene drive, bioengineers can encode DNA with a selected-for trait, which propagates to future generationsand across entire populationswith unnatural speed. This could give mosquitoes resistance to a parasite responsible for malaria or encode them with a gene for female sterilitythus breeding the pests themselves out of existence. But theres also the risk of spreading unwanted mutations and crossbreeding the change into another species. There could be real dangers to releasing organisms into the environment that are out of control at some level genetically, Doudna writes, where theres some trait thats being driven through a population before we understand what the implications of that really are.

Woolly mammoths roaming the earth once again? Its far from easy to do, but scientists are working on just such a Jurassic Park scenario. Ever since I first heard about experiments like these, Ive struggled to decide whether theyre admirable, deplorable, or something in between, writes Doudna. They could enhance our planets biodiversity, but bringing back certain species could also open the door to dangerous pathogens or upset ecosystems.

Since CRISPRs discovery, scientists around the world have been finding new ways to apply gene editing to plants and animals. Here are some of the developments Doudna tracks in A Crack in Creation.

Citrus fruit [Illustration: Alex J. Walker]1. Citrus Fruit:Researchers at South Carolinas Clemson University are employing CRISPR to create citrus trees that are resistant to a disease known as Huanglongbing, or citrus greening, which has devastated the countrys industry over the past decade.

Soybeans [Illustration: Alex J. Walker]2. Soybeans:Using a gene-editing tool called TALEN, Minneapolis-based Calyxt has developed soybeans with an overall fat profile similar to that of olive oil, Doudna writes. The company plans to launch commercial soybean oil next year.

3. Pigs:The University of Missouri has bred pigs that are resistant to porcine reproductive and respiratory syndrome. The virus costs U.S. pork producers more than $500 million annually, Doudna writes, and reduces production by 15%.

Goats. [Illustration: Alex J. Walker]4. Goats:Chinese scientists have applied CRISPR to suppress the gene that controls hair growth in Shanbei goats, prized for their cashmere wool. The enhanced goats produce a third more fur than their counterparts.

5. Monkeys:Researchers in China are harnessing CRISPR to create monkeys that mimic human conditions and diseases, from muscular dystrophy to cancer, which would allow scientists to hunt for disease cures without endangering human lives, Doudna writes.

Chickens. [Illustration: Alex J. Walker]6. Chickens:A team in Australia is exploring ways to rewrite the chicken genome to eliminate the proteins that cause egg allergies in humans. The new eggs could be used in foods and vaccines.

I'm the executive editor of Fast Company and Co.Design.

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The Ethics Of CRISPR - Fast Company

Recommendation and review posted by sam

Bill Lundberg, CSO, CRISPR

CRISPR/Cas9 tech is still at a very early stage of development. But one of the top biotechs looking to make a breakthrough in the clinic got a chance today to explain why one of its preclinical studies helps demonstrate gene editings promise in developing a radically new kind of therapy.

The company is CRISPR Therapeutics $CRSP and its preclinical program focuses on a different kind of approach in treating sickle cell disease as well as beta-thalassemia two diseases triggered by a genetic mutation that slashes the natural production of hemoglobin.

Some people, though, have a genetic mutation that allows their bodies to continue to produce fetal hemoglobin. Its a benign condition that is typically only found by chance. But creating this condition in these patients is a potential cure, and CRISPR Therapeutics made it their showcase program.

Fetal hemoglobin can fully replace adult hemoglobin, CRISPR Therapeutics CSO Bill Lundberg tells me. There are some patients in whom that switch fails to turn off.

Using its gene editing tech, investigators took CD34-positive progenitor cells from patient samples and created this condition in a therapeutic batch. Their abstract presented at the EHA meeting in Madrid on Friday concludes:

Using CRISPR/Cas9 we successfully created gene edits that upregulate HbF in both healthy donor and patient samples. We have also dissected the genotype-phenotype relationship for specific genetic modifications, identifying the editing strategies which are most promising for re-expressing HbF. We have optimized the conditions for modifying HSPCs, including at clinical scale in a GMP-compliant setting, and demonstrated potential safety with no detectable off-target editing. These experiments support the further development of specific CRISPR/Cas9 editing strategies of HSPCs to treat SCD and -Thal patients.

One of the great things about this program, adds the CSO, is that we know what effects it should lead to. We would look for that, look for fetal hemoglobin two to three months in, after patients receive it.

Its worth emphasizing again that this is a preclinical study and all such early lab experiments can at best just set the stage for what has to be tested in humans for an extensive period before any biotech can take a drug to regulators.

That is a long and risky journey at every stage, with plenty of twists expected along the way. And there are several rivals in the field, including Editas $EDIT and Intellia $NTLA. But for CRISPR Therapeutics, it also represents another goal post on the crucial lead-up to the clinic as they start to visualize getting to an application 3 or 4 or 5 years down the road.

Birthing any new technology isnt easy. These kinds of potential revolutions never come cheap or easy, which is why its good for CRISPR Therapeutics to have $290 million in cash. But it will be studied at every step.

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CRISPR crew's lab test spotlights lead program in sickle cell disease, beta-thalassemia - Endpoints News

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New gene editing tools transform disease models and future therapies CRISPR gene editing is taking biomedical research by storm. Providing the ultimate toolbox for genetic manipulation, many new applications for this technology are now being investigated and established. CRISPR systems are already delivering superior genetic models for fundamental disease research, drug screening and therapy development, rapid diagnostics, in vivo editing and correction of heritable conditions and now the first human CRISPR clinical trials.

The continuing patent battle for CRISPR-Cas9 licensing rights and the emergence of new editing systems such as Cpf1 has so far done nothing to slow the advance of CRISPR-Cas9 as the leading gene editing system. There are weekly press releases and updates on new advances and discoveries made possible with this technology; the first evidence is now emerging that CRISPR-Cas9 could provide cures for major diseases including cancers and devastating human viruses such as HIV-1.

The key to CRISPR-Cas9s uptake is its ease of application and design, with retargeting only a matter of designing new guide RNA. It has quickly surpassed TALENs (Transcription Activator-Like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) where editing, now possible with CRISPR, was previously prohibitively complex and time-consuming. As well as correcting gene mutations with scar-less modifications, with CRISPR-Cas9 it is possible to control the expression of entire genes offering longer term expression alteration compared to other methods such as RNAi.

LNA GapmeRs are highly effective antisense oligonucleotides for knockdown of mRNA and lncRNA in vivo or in vitro. Designed using advanced algorithms, the RNase H-activating LNA gapmers offer excellent performance and a high success rate.

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CRISPR-Cas9 systems, tools and basic methodology are very accessible as ready to go toolkits that anyone with lab space and an idea can pick up and start working with. This is thanks largely to the efforts of Addgene and commercial service and product providers. Alongside CRISPR research there are innovations in companion technologies and design software. In response to a growing need, companies such as Desktop Genetics have developed open access software to accelerate CRISPR experimentation and analysis.

It is not all about CRISPR-Cas9 though. Like Cas9, Cpf1 is a DNA-targeting CRISPR enzyme that is also recruited to the target site by sequence homology but with slightly different site requirements. Cpf1 has been reported to be efficient and highly specific in human cells, with low off-target cleavage suggesting a role for Cpf1 in therapeutic applications down the line. Cas13a is an RNA-targeting CRISPR enzyme which is showing promise as a rapid diagnostic tool. Unlike Cas9, the enzyme continues to cut after it has acted on its intended RNA target, a characteristic which has been exploited to develop diagnostic technology for the likes of Zika and Dengue virus. The group behind SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) combined this collateral effect of Cas13a with isothermal amplification and produced rapid DNA or RNA detection at attomolar sensitivity and with single-base mismatch specificity.

A particularly active area of CRISPR activity is the genetic manipulation of patient-derived stem cells to create models for diseases including Parkinsons, cystic fibrosis, cardiomyopathy and ischemic heart disease, to name but a few. With CRISPR it is now possible for researchers to correct disease-causing mutations in patient-derived pluripotent stem cells to create isogenic cell lines to differentiate to any cell type of interest for disease research. Generating these isogenic lines is making it possible, for the first time, to unambiguously show the contribution of gene mutations to a disease phenotype.

Dr Lise Munsie leads the pluripotent stem cell program at CCRM, a Canadian, not-for-profit organisation supporting the development of foundational technologies to support the commercialisation of cell and gene therapies, and regenerative medicine.

Gene editing technology now provides unlimited genetic flexibility to stem cell manipulation. You can target anywhere in the genome with relative ease and make it scar-less, saidDr Munsie.

Dr Munsies program is using CRISPR-Cas9 to produce reporter cell lines (for example with fluorescent protein inserted at a target gene) and isogenic lines from patient iPSCs. In stem cells, CRISPR-Cas9 is introduced with the Cas9 nuclease expressed from plasmid DNA or as purified Cas9 protein and the components are introduced into the cells by transfection or electroporation.

Dr Bjrn Brndl and his colleagues at the Lab for Integrative Biology at the Zentrum fr Integrative Psychiatrie, Universitatsklinikum Schleswig-Holstein, Germany, are also using stem cell gene editing to generate model systems for studying complex neurological disease such as Parkinsons and dyskinesia by correcting mutation in patient lines and introducing these mutations in control cells lines.

One of the biggest contributions of CRISPR to research is the ability to create isogenic stem cell lines. With these, we can create relevant disease models with near-perfect negative controls with the same genomic context varying only in the region of interest. Our goal is to compare disease patient lines with corrected lines by differentiating the induced pluripotent stem cells into neurons and studying differences in the phenotypes. In the biomedical field, we currently have a reproducibility crisis, so with clean and effective tools like isogenic pluripotent stem cells lines, we can improve the reproducibility and validity of our findings. One of the biggest challenges is working with the stem cells which are delicate and much more sensitive to the manipulations required for successful gene editing compared to standard cell lines.

CRISPR has completed upended how cell biology is approached. Being able to copy/paste DNA into the genomes has introduced a lot of ways of thinking about a problem. Genome editing has introduced engineering into the cell biology toolbox. saidDr Brndl.

An alarming number of bacteria are now resistant to our most effective antibiotics. The antibiotic resistance crisis has been given more of the attention it deserves thanks to initiatives from the WHO, UN, NICE and others but, in truth, the situation has been critical for over a decade. No new antibiotics have come out of pharma companies in the last 10 years and interest in their development has waned. Pharma companies are reluctant to invest the large sums required to develop new antimicrobials because of the inevitable resistant strains that will quickly follow and subsequent restrictions on their usage to preserve efficacy.

In short, we need a miracle, but the answer could come from CRISPR. Companies such as Nemesis Bioscience and Eligo Bioscience are developing antimicrobial technology and treatments made possible by CRISPR technology. Both technologies use modified bacteriophage as delivery vehicles for CRISPR-Cas9 gene editing systems that target and inactivate either virulence genes or the resistance genes themselves, leaving the rest of the microbiome intact.

Nemesis Bioscience employs CRISPR to target known bacterial resistance genes to deactivate them in situ and re-sensitise virulent bacteria making existing antibiotics effective again. Dr Frank Massam, CEO at Nemesis Biosciences explains, Killing bacteria stimulates resistance mutations we reasoned it would make more sense to inactivate bacterias ability to resist antibiotics and therefore make existing antibiotics work again. This approach would also mean that newly developed antibiotic assets could be protected from resistance, thereby increasing pharmas ROI and so making antibiotic development attractive again.

Nemesis Biosciences Symbiotics are based on modified CRISPR-Cas9 which enables highly multiplexed guide RNA targeting. Our first expression cassettes encode the S. pyogenes Cas9 plus a CRISPR array encoding guide RNAs that can target for inactivation members of 8 families of beta-lactamase genes. We call them the VONCKIST families, these are: VIM, OXA, NDM, CTX-M, IMP, SHV and TEM. The beta-lactamases encoded by these families are able to degrade >100 different types of beta-lactam antibiotics saidDr Massam.

The symbiotics are delivered by phage Transmids delivery vehicles based on phage architecture that deliver the DNA and then drop off. Once the Symbiotic is inside the bacteria, it can then spread further by conjugation from the edited bacteria to others it encounters, remaining invisible to the immune system. This provides both therapeutic applications as well as prophylactic ones in a probiotic delivery system to disarm the microbiome of antimicrobial-resistant bacteria. The technology is applicable to all bacteria, all antibiotic classes and all known resistance mechanisms and Nemesis have initially targeted resistant E. coli for in vivo testing.

Traditional small-molecule antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Eligo Biosciences flagship technology SSAMS eligobiotics, uses reprogrammed Cas9 targeted to bacterial virulence or resistance genes delivered by phagemids to produce selective killing of virulent and antibiotic resistant bacteria, leaving all other bacteria unaffected. The Eligo platform is being adapted for other microbial applications including in situ detection of specific live bacterial strains in complex microbiome samples and in situ expression of therapeutics protein to modulate and engineer host-microbiome interactions.

CRISPR-based therapies for human diseases could bring profound benefits to medicine, but there are many hurdles still to overcome. Despite the high degree of specificity of the CRISPR system, the induction of off-target mutations, at sites other than the intended target, is still a major concern especially in the context of therapeutic applications for heritable disease, and there are still considerable safety concerns about using CRISPR in humans. Assays for investigating the intended (on-target) and unintended (off-target) effects of CRISPR guides on in vitro and in vivo models are still in their infancy. The second major challenge is the development of safe carrier systems for CRISPR-Cas9 delivery to human cells in vivo.

Nonetheless, exciting progress is being made in the application of CRISPR gene editing to the treatment of heritable diseases for which there are only symptomatic treatments available, such as retinal myopathy where demonstrated recovery has been reported in a mouse model, and Duchenne muscular dystrophy, where the disease phenotype is reversed in mouse cells in vivo. We will also soon see the completion of the first clinical trials using CRISPR to try and correct genetic defects in vivo, the results of which are eagerly awaited.

There are a growing number of researchers from many disciplines collaborating to bring ambitious CRISPR-based insight, technology and therapeutics into the clinic. As CRISPR continues to undergo technical improvements, the prospects for these applications continues to look promising and as they move rapidly towards reality.

References

1. Yin, C., Zhang, T., Qu, X., Zhang, Y., Putatunda, R., Xiao, X., ... & Qin, X. (2017). In vivo excision of HIV-1 provirus by saCas9 and multiplex single-guide RNAs in animal models. Molecular Therapy.)

2. Hough SH, Kancleris K, Brody L, Humphryes-Kirilov N, Wolanski J, Dunaway K, Ajetunmobi A, Dillard V. Guide Picker is a comprehensive design tool for visualizing and selecting guides for CRISPR experiments. BMC bioinformatics. 2017 Mar 14;18(1):167.

3. Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., Essletzbichler, P., ... & Koonin, E. V. (2015). Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell, 163(3), 759-771.

4. Kleinstiver, B. P., Tsai, S. Q., Prew, M. S., Nguyen, N. T., Welch, M. M., Lopez, J. M., ... & Joung, J. K. (2016). Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells. Nature biotechnology, 34(8), 869-874.

5. Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Dy AJ, Joung J, Verdine V, Donghia N, Daringer NM, Freije CA, Myhrvold C. Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017 Apr 13:eaam9321

6. Bikard, D., Euler, C. W., Jiang, W., Nussenzweig, P. M., Goldberg, G. W., Duportet, X., ... & Marraffini, L. A. (2014). Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nature biotechnology, 32(11), 1146-1150.

7. Zhang, X. H., Tee, L. Y., Wang, X. G., Huang, Q. S., & Yang, S. H. (2015). Off-target effects in CRISPR/Cas9-mediated genome engineering. Molecular Therapy-Nucleic Acids, 4, e264.

8. Yu, W., Mookherjee, S., Chaitankar, V., Hiriyanna, S., Kim, J. W., Brooks, M., ... & Swaroop, A. (2017). Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice. Nature Communications, 8.

9. Long, C., Amoasii, L., Mireault, A. A., McAnally, J. R., Li, H., Sanchez-Ortiz, E., ... & Olson, E. N. (2016). Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science, 351(6271), 400-403.

10. Nelson, C. E., Hakim, C. H., Ousterout, D. G., Thakore, P. I., Moreb, E. A., Rivera, R. M. C., ... & Asokan, A. (2016). In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science, 351(6271), 403-407.

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CRISPR: Emerging applications for genome editing technology - Technology Networks

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June 26, 2017 The researchers used the engineered viral vector AAV-PHP.S to label neurons lining the digestive tract with a cocktail of three distinct fluorescent proteins. Due to the stochastic uptake of viruses encoding either a blue, green or red fluorescent protein, cells are labeled with a wide range of hues. This multicolor approach can be used to differentiate neighboring neurons for morphology and tracing studies. Credit: Chan et al., Gradinaru Lab; Nature Neuroscience

Viruses have evolved to be highly effective vehicles for delivering genes into cells. Seeking to take advantage of these traits, scientists can reprogram viruses to function as vectors, capable of carrying their genetic cargo of choice into the nuclei of cells in the body. Such vectors have become critical tools for delivering genes to treat disease or to label neurons and their connective fibers with fluorescent colors to map out their locations. Because viral vectors have been stripped of their own genes and, thereby, of their ability to replicate, they are no longer infectious. Therefore, achieving widespread gene delivery with the vectors is challenging. This is especially true for gene delivery to hard to reach organs like the brain, where viral vectors have to make their way past the so-called blood-brain barrier, or to the peripheral nervous system, where neurons are dispersed across the body.

Now, to enable widespread gene delivery throughout the central and peripheral nervous systems, Caltech researchers have developed two new variants of a vector based on an adeno-associated virus (AAV): one that can efficiently ferry genetic cargo past the blood-brain barrier; and another that is efficiently picked up by peripheral neurons residing outside the brain and spinal cord, such as those that sense pain and regulate heart rate, respiration, and digestion. Both vectors are able to reach their targets following a simple injection into the bloodstream. The vectors are customizable and could potentially be used as part of a gene therapy to treat neurodegenerative disorders that affect the entire central nervous system, such as Huntington's disease, or to help map or modulate neuronal circuits and understand how they change during disease.

The work was done in the laboratory of Viviana Gradinaru, assistant professor of biology and biological engineering, Heritage Medical Research Institute Investigator, director of the Center for Molecular and Cellular Neuroscience in the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech, and principal investigator of the Beckman Institute's CLOVER (CLARITY, Optogenetics, and Vector Engineering Research) Center.

A paper describing the research appears online in the June 26 issue of Nature Neuroscience.

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"We have now developed a new collection of viruses and tools to study the central and peripheral nervous systems," says Gradinaru. "We are now able to get highly efficient brain-wide delivery with just a low-dose systemic injection, access neurons in difficult-to-reach regions, and precisely label cells with multiple fluorescent colors to study their shapes and connections."

Gradinaru and her team modified the external surface of an AAV developed in 2016, engineering the virus's shell, or capsid, to allow it to more efficiently deliver genes to cells in the brain and spinal cord following intravenous injection. They named the new virus AAV-PHP.eB.

The team also developed an additional capsid variant they call AAV-PHP.S, which is able to transduce peripheral neurons.

"Neurons outside of the central nervous system have many functions, from relaying sensory information to controlling organ function, but some of these peripheral neural circuits are not yet well understood," says Ben Deverman, senior research scientist and director of the Beckman Institute's CLOVER Center. "The AAV-PHP.S vector that we developed could help researchers study the activity and function of specific types of neurons within peripheral circuits using genetically-encoded sensors and tools to modulate neuronal firing with light or designer drugs, respectively."

The new AAV vectors can also deliver genes that code for colorful fluorescent proteins; such proteins are useful in identifying and labeling cells. In this process, multiple AAVseach carrying a distinct colorare mixed together and injected into the bloodstream. When they reach their target neurons, each neuron receives a unique combination of colors, thereby giving it a visually distinct hue that makes it easier for the researchers to distinguish its fine details from those of its neighbors. Furthermore, the team devised a technique to control the number of neurons labeledlabeling too many neurons makes it impossible to distinguish individual onesthat allows researchers to visualize individual neuron shapes and trace their connecting fibers through intact tissues using another technology the Gradinaru laboratory has helped develop, known as tissue clearing.

"Usually, when researchers want a mouse or other animal model to express fluorescent proteins in certain cells, they need to develop genetically modified animals that can take months to years to make and characterize," says former graduate student and first author Ken Chan (PhD '17). "Now with a single injection, we can label specific cells with a variety of colors within weeks after the injection."

"For our new systemic viral vectorsAAV PHP.S and AAV PHP.eBthere are many potential uses, from mapping circuits in the periphery and fast screening of gene regulatory elements to genome editing with powerful tools such as CRISPR-Cas9," says Gradinaru. "But perhaps the most exciting implication is that our tools, when paired with appropriate activity modulator genes, could enable non-invasive deep brain modulation for the treatment of neurological diseases such as Parkinson's disease."

The paper is titled "Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems."

Explore further: Delivering genes across the blood-brain barrier

More information: Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems, Nature Neuroscience (2017). DOI: 10.1038/nn.4593

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It may be true that Brain is Far Away. Rather than on Brains, Work on Intestines first. Just Feed Viruses through Mouth. Find Viruses That can Specifically line up Only The Interior of Mouse Intestines; Each TYPE of Virus should act as MAGNET for a Huge Collection of DIFFERENT TYPE OF BACTERIUM. Then, See Differences in their Effects on Mice! Also, in a Negative Way...i.e Driving Them Away...Making the Intestines Unlivable for those Bacteria that felt it as their home until then. Of course, Start working with Bacteria Natural to Intestinal Mucosa of Mice ONLY First !

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Novel viral vectors deliver useful cargo to neurons throughout the brain and body - Medical Xpress

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OK, today I want to talk about hormones which ones are important and why. Hormones have just as much impact on your health as the three other big pieces of the puzzle physical health, mental health and nutrition. Dont believe me? Well, you will by the end of this, so keep reading! This will be a very broad overview and I havent included all hormones, just what I call the big hitters. In later columns, well dive deeper into individual hormones.

Vitamin D

Vitamin D is technically a pro-hormone that we get mainly from being out in the sun. Other sources include cod liver oil, calcium-rich foods, egg yolk and supplementation. Almost everyone is deficient in Vitamin D. I take a Vitamin D. The biggest areas of benefit include significantly decreasing risk of cancer (by blocking progression of pre-cancerous cells) and lowering heart disease rates. It can also improve testosterone levels, calcium absorption, bone health, blood pressure control and lower autoimmune disease rates. Its one of the first areas I recommend for a quick improved health intervention in most of my patients.

Thyroid

Your thyroid is important, and low levels of thyroid hormones can significantly impact health. Your thyroid regulates metabolism, energy and body temperature. When its healthy, it increases protein synthesis, lowers cholesterol, increases fat breakdown and improves cognition. When its low, there are over 200 symptoms you could have. The most significant include fatigue, depression, weight gain, dry skin, brittle nails, thin hair, brain fog, constipation and high cholesterol. Women, especially those ages 40-60, are more prone to low thyroid levels compared to men although we do see it in men as well.

Adrenal

Another common area impacting health is your adrenals (you have two of them they rest just above your kidneys). When you are startled and have that body shock feeling, thats the adrenals releasing adrenaline. When there is longer term stress, the adrenals release cortisol. When stress continues and cortisol gets depleted, you move towards what we call adrenal fatigue. Unfortunately, due to our inherent culture of go-go-go, adrenal fatigue syndrome is very common. Also, it usually takes a long time (4-12 months) to resolve once addressed. Stress management is a key to reducing your risk for adrenal fatigue and improving your health. Well discuss stress management techniques in a later column.

Sex hormones

Testosterone, estrogen, and progesterone are all considered sex hormones. The name is misleading as these hormones are definitely not just about sex. Thats not even how the word sex is meant here. Anyway, I could go on for many moons on this subject as Im passionate about it but well hit some highlights here. In general, women need estrogen, progesterone and testosterone. Men need testosterone and estrogen. People usually think of testosterone as only for men and estrogen as only for women but thats not the case. Men and women need estrogen and testosterone to benefit their health but the levels needed are different. As an aside, sex hormone optimization is complex and you need a healthcare provider who specializes in this to address and manage it properly as there are risks to mismanagement. Testosterone helps your body with sex drive, erections (in men), muscle strength, mood, energy, bone strength, as well as decreasing heart disease, cholesterol and diabetes risks to name a few benefits. Estrogen and progesterone can affect mood, sex drive, breast growth (particularly in women), urinary tract infection risk, cholesterol, bone strength, cognition, Alzheimers risk, skin health and sleep...again, to name just a few areas. Progesterone, in particular, is good at helping with sleep.

For women, these sex hormones can be deficient before menopause, but definitely deficient after. Ten to 15 years ago, there was concern for hormone replacement after menopause and several post-menopausal women abruptly stopped hormone replacement. We now know that likely put them in a higher health risk category than if theyd stayed on them. Also, since then, weve learned more and really see where theres a benefit in maintaining these hormone levels with appropriate surveillance by a qualified healthcare provider.

For men, testosterone, in particular, got a bad rap 4-8 years ago with a concern for worsening heart disease risk, and historically there has been a concern for prostate cancer risk. We will address these individually at length in upcoming columns but the short of it is this: there does not appear to be an increased risk for prostate cancer with normal compared to low testosterone levels (the data actually shows an increasing incidence in the low testosterone groups) and, in most patients, theres an improvement in heart health and lowering of heart disease risk with normal testosterone levels compared to low (similar to above, the data points towards increased heart disease risk at low testosterone levels compared to normal).

I know I threw a lot at you here, but thats a super-high bird's eye look at the impact of hormones on health. Keeping hormone levels optimized naturally, or if needed through supplementation, improves your chance for more functional years and an improved quality of life!

Dr. Thomas is a board-certified physician who operates Complete Health Integrative Wellness Clinic and Thomas Urology Clinic in Starkville, Mississippi.

This newspaper column is for informational purposes only and is, under no circumstances, intended to constitute medical advice or to create or continue a physician-patient relationship. If you have a medical emergency, you should immediately seek care from your nearest emergency room, and if you have specific health questions, you should consult your own physician.

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Important hormones for your health - Meridian Star

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AUGUSTA, Ga. (WJBF)-Augusta Pride Weekend 2017 has arrived.

This is the eighth annual pride celebration in Augusta, and this year, organizers are hoping between 12,000 and 15,000 people attend the weekend of celebration.

Alyssa Fredericks of Thomson came to Beats on Broad, the Friday night celebration at the common, with her girlfriend, andshe says she feels the CSRA is a pretty welcoming place for the LGBTQ community.

Its good to be out here with everybody, Fredericks said. Its like a community as one.

Even though its a party, some groups are taking advantage of the celebration to offer important health services, includingfree HIV testing.

We caught up with a volunteer from the Equality Clinic of Augusta, which is a free student-run clinic for uninsured and underinsured people.

A lot of our patients are from the LGBTQ population, said Matthew Luo, who is treasurer of the Equality Clinic of Augusta.

Luo says about 70 percent of their patients are transgender people seeking hormone replacement therapy. He says they are one of the only clinics in the region that provides that service to those in need.

We have people coming from Charleston, from Mississippi from like Kentuckyall over the Southeast to come, he said. They drive hours and hours to come to our clinic because were one of the only people that offers this service.

Its a reflection of what Augusta pride is trying to dooffering people in the CSRA and beyond a chance to be themselves.

Its about love, respect, tolerance, being able to live your most authentic life, said Augusta Pride President Lonzo Smith.

The pride parade kicks off on Broad Street at 10:30 a.m. Saturday.After that the pride festival will be at the Augusta Common till 5 p.m.

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Ottawa Sun

Jonathan Pitre still ailing as doctors search for answers Ottawa Sun Pitre checked back into hospital earlier this month just three days after being released following a stem cell transplant that had successfully taken root in his bone marrow. Bone marrow stem cells produce most of the body's blood cells, and are ... and more »

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Jonathan Pitre still ailing as doctors search for answers - Ottawa Sun

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