Category Archives: Molecular Medicine

A German research institute is offering scientists a 1,000 (847) bonus if they publish null results or a replication study as part of its bid to reshape academic incentives.

The unusual offer made to the Berlin Institute of Healths 7,000 researchers is part of a programme to boost research transparency and confidence in science amid international concerns that the pressure to produce positive experimental results that are more likely to be published by leading journals drives some scientists to manipulate data.

The institute, which combines the Charit Universittsmedizin Berlin university hospital and the Max Delbrck Center for Molecular Medicine, is also offering the 1,000 bonus if researchers publish a preregistered pre-clinical study or a paper that reuses data previously published by others.

There are also financial incentives available for scholars who publish their experiments raw data. Some might be disappointed to learn, however, that the money goes towards a scientists research funds rather than into their personal bank account.

Ulrich Dirnagl, director of Charits department of experimental neurology, told Times Higher Education that the bonuses which have been awarded over the past two years had sparked useful debate about research integrity.

You cannot do major research with 1,000, but it might help a student travel to a research conference, said Professor Dirnagl, who is the founding director of the Quest (Quality, Ethics, Open Science and Translation) Center for Transforming Biomedical Research.

It is mainly a way to start a conversation about the topic.

While scientists are invited to apply for the bonuses and normally get them, the institute has also recently been seeking out good practice to reward, Professor Dirnagl said.

We have been mining the publication records of our researchers, pulling out papers where open data has been provided and giving them the money, he said.

Such incentives helped to complement Germanys more traditional performance-oriented system, in which journal impact factors and the ability to attract third-party funding were prized by promotion and hiring panels, Professor Dirnagl explained.

Since we are not convinced this is the best way of doing things, we wanted to think how to complement this structure with rewards that are individually based, he said.

Those who accrue several bonuses could find they gain quite a nice supplement to their research funds, Professor Dirnagl added.

The Berlin institute has also applied the same principles to its promotion practices, with those applying for a professorial post having to outline how they have encouraged responsible science.

Applicants must describe their top five research papers without naming the publication in which they appeared, a move that seeks to combat over-reliance on journal reputation and to encourage engagement with the substance of the work.

We are trying to nudge the process to get them to consider different factors and ideas, said Professor Dirnagl. We are perhaps rewarding things that should be normal process, but it needs to be done.

We hope this programme can provide a model for widespread adoption by other research institutions globally.

The initiative is outlined in a paper published in Plos Biology on 11February.

jack.grove@timeshighereducation.com

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Scientists offered 1000 to publish null results - Times Higher Education (THE)

SALT LAKE CITY, Feb. 14, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (MYGN), a leader in molecular diagnostics and precision medicine, announced that it is presenting new data at the American Society of Clinical Oncology Genitouranary Cancer Symposium in San Francisco, California. The key finding is that Prolaris accurately predicts which men with intermediate or high-risk prostate cancer will benefit from multi-modality therapy and which can avoid unnecessary treatment.

While it has been demonstrated that multi-modality therapy can improve overall survival in prostate cancer, it comes at the risk of increased morbidity and increased cost to the healthcare system, said Jonathan Tward M.D., PhD, associate professor in the Department of Radiation Oncology at the University of Utah. Prolaris provides a unique tool that can accurately predict which patients with high-risk prostate cancer will truly benefit from multi-modality therapy and conversely which patients with lower risk can safely avoid such treatments.

The investigators evaluated 718 men with intermediate or high-risk prostate cancer. The Prolaris score predicted metastasis (HR=3.75; p=1.6x10-16) and remained highly predictive after adjusting for the effect of standard clinical and pathological features (HR=4.30; p=4.4x10-8). In the study, patients above the high-risk threshold with a Prolaris score of greater than 2.112, which comprised approximately 44 percent of the men in the study, saw a statistically significant benefit from multi-modality therapy leading to a reduction in risk of metastases. Patients below the high-risk threshold saw no benefit from multi-modality therapy, suggesting that such patients may be able to avoid additional morbidity associated with additional treatment.

AboutProlarisProlaris is a genetic test developed by Myriad that directly measures tumor cell growth. The Prolaris test paired with both prostate-specific antigen (PSA) and Gleason provides the level of aggressiveness of a patients individual prostate cancer. PSA and Gleason only have the ability to identify how far the cancer has progressed thus far. However, when these are combined with a Prolaris test score, patients get an accurate assessment of how aggressively that cancer will progress over the next ten years. For more information visit:www.prolaris.com

About Myriad GeneticsMyriad Genetics Inc. is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Lynparza is a registered trademark of AstraZeneca.

Safe Harbor StatementThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the Company presenting new data at the American Society of Clinical Oncology Genitouranary Cancer Symposium in San Francisco, California; patients below the high-risk threshold being able to avoid additional morbidity associated with additional treatment; and the Companys strategic imperatives under the caption About Myriad Genetics. These forward-looking statements are managements present expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those described or implied in the forward-looking statements. These risks include, but are not limited to: the risk that sales and profit margins of the Companys existing molecular diagnostic tests and pharmaceutical and clinical services may decline or will not continue to increase at historical rates; risks related to the Companys ability to successfully transition from its existing product portfolio to its new tests; risks related to changes in the governmental or private insurers reimbursement levels for the Companys tests or the Companys ability to obtain reimbursement for its new tests at comparable levels to its existing tests; risks related to increased competition and the development of new competing tests and services; the risk that the Company may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that the Company may not successfully develop new markets for its molecular diagnostic tests and pharmaceutical and clinical services, including the Companys ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying the Companys molecular diagnostic tests and pharmaceutical and clinical services tests and any future tests are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating the Companys laboratory testing facilities; risks related to public concern over the Companys genetic testing in general or the Companys tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to the Companys ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to the Companys ability to successfully integrate and derive benefits from any technologies or businesses that it licenses or acquires; risks related to the Companys projections about the potential market opportunity for the Companys products; the risk that the Company or its licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying the Companys tests; the risk of patent-infringement claims or challenges to the validity of the Companys patents; risks related to changes in intellectual property laws covering the Companys molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that the Company may be unable to comply with financial operating covenants under the Companys credit or lending agreements; the risk that the Company will be unable to pay, when due, amounts due under the Companys credit or lending agreements; and other factors discussed under the heading Risk Factors contained in Item 1A of the Companys most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in the Companys Quarterly Reports on Form 10-Q or Current Reports on Form 8-K.

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New Study Demonstrates the Ability of Prolaris to Predict Which Men With Prostate Cancer Will Benefit from Multi-Modality Therapy - Yahoo Finance

Nanotechnology will transform our lifes, our economy, our future. The book of the Oxford professor of biological physics, Sonia Contera, Nano Comes To Life: How Nanotechnology Is Transforming Medicine and the Future of Biology (Amazon.com, Amazon.co.uk, Amazon.de, Amazon.fr), explains why and how.

Nanotechnologies allow scientists to visualize, interact with, manipulate and create matter at the nanometer scale. Nanotechnology can manipulate the building blocks of life and, therefore, life itself because proteins and DNA are nano-size.

According to Sonia Contera, health and longevity will be affected. Nanoscale machines can target individual cancer cells and deliver drugs more effectively. Nanoantibiotics can fight resistant bacteria and makes it possible to engineer tissues and organs for research, drug discovery and transplantation.

Nanotechnology directly links the macroscopic world of our perceptions with the nanoscopic world of individual biomolecules. To restore humans to perfect health, we would need to know how molecules work in a specific environment, why and how they malfunction in a desease and who to reach them, target them, deactivate or activate them. To cure, we need to go from the macroscopic size of the doctor to the nanometer scale of biomolecules. Sonia Conteras book tries to show how far we have come so far.

Nanotechnology has attracted physical scientists to biology. In the last decades of the 20th century, artificial nanomaterials and the tools of nanotechnology came into existence. Physcial scientists sought to know how and why biology first constructed itself using nano-size building blocks in the medium of (salty) water. The coupling of physics and chemistry give rise to biological function. Scientists focused on using nanotechnologys methods to learn the workings of proteins, DNA and other important nano-size biomolecules. They became biological physicists. Others, more practical, saw opportunities to design nanomaterials that could be used to address disease, improving on current pharmacological treatments; they became nanomedicine scientists.

Cross-disciplinary activity led to the development of tools specifically built for studying biological processes and their nano-actors in physiological conditions. Nano-bioscientists eroded the boundaries between materials sciences, physics, chemistry and biology.

The last decades saw the emergence of quantitative biology. Physicists try to create mathematical models of biological processes. They try to predict the behavior of specific biological processes in the computer (in silico), without experiments. This shall allow to progressively abandon the trial-and-error methods of the traditional biological, medical and pharmacological sciences which are slow, costly and often lead to inefficient new drugs.

Biological physics, the help of algorithms, the analysis of biological big data and AI will lead to increasingly (more) accurate and smart models of life. However, knowing the workings of the building blocks (of life) is not enough to predict the behaviour of the whole: at larger scales, biology exhibits behaviors that the smaller constituents do not exhibit, or that cannot be explained from the relationships between their molecular building blocks. Sonia Contera explains that this is because complexly organized matter presents collective phenomena arising from cooperative interactions between the building blocks (these properties emerge). Examples are cellular movements, mechanical vibrations in the brain, electrical signaling across the membranes of cells, changes in the shape or stiffness, none of which can be predicted from just knowing the molecules that constitute a particular structure. For instance, nanotechnology would allow simultanously targeting the molecular, the cellular and the issue-level biology of a tumor.

Biology, mathematics, physics and engineering sciences used in nanotechnology will radically change, the way we find, interpret and treat disease. Nanotechnology will transform biology and medicine. Sonia Contera explores the complexity of biology, the birth of DNA technology, DNA nanorobotics, nanomedicine, recreating tissues and organs, addresses issues such as fear of technology, technology and equality. These are just a few take-aways from this substantial book written for non-specialists.

The author writes that we as human beings have no other choice than to mature to become part of the whole in a physical, economic and social sense. We have to advance into the construction of a new relationship with nature that allows our survival.

Sonia Contera: Nano Comes To Life: How Nanotechnology Is Transforming Medicine and the Future of Biology. Hardcover, Princeton University Press, November 2019, 216 pages. Order the book, the source for this article, from Amazon.com, Amazon.co.uk, Amazon.de, Amazon.fr.

For a better reading, quotations and partial quotations in this book review are not put between quotation marks.

Book review added on February 14, 2020 at 16:14 German time.

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How nanotechnology is transforming medicine and the future of biology - Cosmopolis

ROCKVILLE, Md., Feb. 13, 2020 /PRNewswire/ --National Foundation for Cancer Research (NFCR) (NFCR) announced today that Susan Band Horwitz, Ph.D., has been selected to receive the 2020 Szent-Gyrgyi Prize for Progress in Cancer Research. The Prize selection committee awarded Dr. Horwitz for pioneering the understanding, at the molecular level, of the mechanisms of action and resistance of multiple effective and widely utilized anti-tumor drugs, particularly Taxol, of natural product origin.

A Distinguished Professor and Rose C. Falkenstein Chair in Cancer Research at the Albert Einstein College of Medicine in New York, Dr. Horwitz most notably elucidated the mechanism of action of Taxol, a natural product obtained from the yew tree. Specifically, in the late 1970s and early 1980s, she discovered that the compound, whose generic name is paclitaxel, binds to microtubules in cells, stabilizing them, thereby leading to cell cycle arrest and subsequent cell death. This body of work enabled the successful translation of the drug into the clinic, and it is now one of the most frequently prescribed medications in the world for the treatment of ovarian, breast and lung cancers.

Her work with Taxol, which became a blockbuster drug, led to an interest in microtubule stabilizing agents, which has resulted in the U.S. Food and Drug Administration's approval of docetaxel (Taxotere), ixabepilone (Ixempra), carbazitaxal (Jevtana) and new formulations, including, most notably, nabpaclitaxel (Abraxane). Additionally, she has made major contributions to the understanding of many other naturally occurring molecules or their derivatives which serve as cancer treatments. These include camptothecin, bleomycin and the epipdophyllotoxins.

Funded continuously by NFCR for the past two decades, Dr. Horwitz's work now includes research into which isoforms of tubulin may have a role in resistance to Taxol, as well as efforts that may help predict which patients would be more likely to respond well to the drug.

The 2020 Szent-GyrgyiPrize's independent selection committee was unanimous in its decision to recognize Dr. Horwitz's contributions. She will be honored at an award ceremony held Saturday, April 25, at the National Press Club in Washington, D.C. Media are invited and encouraged to attend.

"Dr. Horwitz has made several seminal contributions, including the major finding of the mechanism of action of a drug that has been deployed in the treatment of over a million cancer patients," exclaimed Steven A. Rosenberg, M.D., Ph.D., chair of the 2020 Prize selection committee, surgery branch chief of the U.S. National Cancer Institute and winner of the 2019 Szent-Gyrgyi Prize. "She has profoundly impacted and improved the treatment of cancer patients."

"Matching the key criteria for this prestigious prizeher seminal and extensive scientific achievements and lasting impact in saving patients' livesplaces Dr. Horwitz in the uppermost tier of cancer researchers," said Sujuan Ba, Ph.D., co-chair of the 2020 Prize selection committee and president and CEO of NFCR. "We are so proud that Dr. Horwitz becomes the third National Foundation for Cancer Research supported scientist to be awarded the Szent-Gyrgyi Prize, after Dr. Web Cavenee in 2007 and Dr. Harold Dvorak in 2006."

"I am deeply honored by this award from the National Foundation for Cancer Research and the Szent-Gyrgyi Prize selection committee," stated Dr. Horwitz. "It is a real privilege to be among the winners of this prize, all of whom have greatly advanced cancer research and treatment. And this award is also a testament to all the students, fellows and visiting scientists who contributed to the research conducted in my lab over the years."

About the Szent-Gyrgyi Prize for Progress in Cancer ResearchThe Szent-Gyrgyi Prize for Progress in Cancer Research was established in 2006 by the National Foundation for Cancer Research in honor of its co-founder, Albert Szent-Gyrgyi, M.D., Ph.D., recipient of the 1937 Nobel Prize for Physiology and Medicine. The award recognizes and honors scientists who have made seminal discoveries or produced pioneering bodies of work that have resulted in, or led toward significant contributions to, cancer prevention, diagnosis and treatment with a high impact of saving people's lives. Its past recipients (and their associated institutions at the time of the award) are:

The 2020 Szent-Gyrgyi Prize's selection committee was comprised of the following persons, each an authority in the field of cancer research:

About the National Foundation for Cancer ResearchThe National Foundation for Cancer Research (NFCR) is a 501(c)(3) non-profit organization that provides scientists in the lab the funding they need to make and apply game-changing discoveries in cancer treatments, detection, prevention and, ultimately, a cure. It has distinguished itself in the cancer sector by emphasizing long-term, transformative research often overlooked by other major funding sources. With the help of more than 5.3 million individual donors over the last 47 years, NFCR has delivered more than $380 million in funding to public education and cancer research leading to several important, life-saving discoveries. For more information, visit http://www.nfcr.org.

CONTACT:National Foundation for Cancer ResearchBradley Gillenwater, Senior Director for Global Program DevelopmentE-mail: bgillenwater@nfcr.org / Phone: 301-961-9161

View original content:http://www.prnewswire.com/news-releases/2020-szent-gyorgyi-prize-awarded-to-a-pioneering-researcher-who-has-unlocked-workings-of-cancer-drugs-of-natural-product-origin-301003660.html

SOURCE National Foundation for Cancer Research

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2020 Szent-Gyrgyi Prize Awarded to a Pioneering Researcher Who Has Unlocked Workings of Cancer Drugs of Natural Product Origin - BioSpace

In August of 2011, Carl June and his team published a landmark paper showing their CART treatment had cleared a patient of cancer. A year-to-the-month later, Jennifer Doudna made an even bigger splash when she published the first major CRISPR paper, setting off a decade of intense research and sometimes even more intense public debate over the ethics of what the gene-editing tool could do.

Last week, June, whose CART work was eventually developed by Novartis into Kymriah, published in Sciencethe first US paper showing how the two could be brought together. It was not only one of the first time scientists have combined the groundbreaking tools, but the first peer-reviewed American paper showing how CRISPR could be used in patients.

June used CRISPR to edit the cells of three patients with advanced blood cancer, deleting the traditional T cell receptor and then erasing the PD1 gene, a move designed to unleash the immune cells. The therapy didnt cure the patients, but the cells remained in the body for a median of 9 months, a major hurdle for the therapy.

Endpoints caught up with June about the long road both he and the field took to get here, if the treatment will ever scale up, and where CRISPR and other advancements can lead it.

The interview has been condensed and edited.

Youve spoken in the past about howyou started working in this field in the mid-90s after your wife passed away from cancer. What were some of those early efforts? How did you start?

Well, I graduated from high school and had a low draft number [for the Vietnam War] and was going to go to study engineering at Stanford, but I was drafted and went into the Naval Academy in 1971, and I did that so I wouldnt have to go to the rice fields.

The war ended in 73, 74, so when I graduated in 1975, I was allowed to go to medical school, and then I had a long term commitment to the Navy because they paid for the Acadamy and Medical school. And I was interested in research and at the time, what the Navy cared about was a small scale nuclear disaster like in a submarine, and like what happened at Chernobyl and Fukushima. So they sent me to the Fred Hutchinson Cancer Center where I got trained in cancer, as a medical oncologist. I was going to open a bone marrow transplant center in Bethesda because the Navy wanted one in the event of a nuclear catastrophe.

And then in 1989, the Berlin Wall came down and there was no more Cold War. I had gone back to the Navy in 86 for the transplant center, which never happened, so then I had to work in the lab full time. But in the Navy, all the research has to be about combat and casualty. They care about HIV, so my first papers were on malaria and infectious disease. And the first CAR-T trials were on HIV in the mid-90s.

In 96, my wife got diagnosed with ovarian cancer and she was in remission for 3-4 years. I moved to the University of Pennsylvania in 1999 and started working on cancer because I wasnt allowed to do that with the Navy. My wife was obviously a lot of motivation to do that. She passed away in 2001. Then I started working with David Porter on adoptive transfer T cells.

I got my first grant to do CAR-T cells on HIV in 2004, and I learned a whole lot. I was lucky to have worked on HIV because we did the first trials using lentiviruses, which is an engineered HIV virus.

I was trained in oncology, and then because of the Navy forced to work on HIV. It was actually a blessing in disguise.

So if you hadnt been drafted, you wouldve become an engineer?

Yes. Thats what I was fully intending. My dad was a chemical engineer, my brother is an engineer. Thats what I thought I was going to do. No one in my family was ever a physician. Its one of those many quirks of fate.

Back then, we didnt have these aptitude tests. It was just haphazard. I applied to three schools Berkeley, Stanford and Caltech and I got into all three. It was just luck, fate.

And it turned out when I went to the Naval Academy, they had added a pre-med thing onto the curriculum the year before, so thats what I did when I started, I did chemistry.

I wouldve [otherwise] been in nuclear submarines. The most interesting thing in the Navy then was the nuclear sub technology.

You talked about doing the first CAR-T trials on HIV patients because thats where the funding was. Was it always in your head that this was eventually going to be something for cancer?

So I got out of the Navy in 99 and moved to Penn. I started in 98 working on treating leukemia, and then once I got to Penn, I continued working one day a week on HIV.

Its kind of a Back-to-the-Future thing because now cancer has paved out a path to show that CART cells can work and put down the manufacturing and its going to be a lot cheaper making it for HIV. I still think thats going to happen.

Jim Riley, who used to be a postdoc in my lab, has some spectacular results in monkeys with HIV models. They have a large NIH and NIAID research program.

So were going to see more and more of that. The CAR technology is going to move outside of cancer, and into autoimmune and chronic infections.

I want to jump over to cytotoxic release syndrome (CRS)because a big part of the CRISPR study was that it didnt provoke this potentially deadly adverse effect. When did you first become aware that CRS was going to be a problem?

I mean we saw it in the very first patient we treated but in all honesty, we missed it. Im an MD, but I dont see the patient and David Porter tookcare of the first three patients and our first pediatric patient,Emily Whitehead.

In our first patients, 2 out of 3, had complete remission and there were fevers and it was CRS but we thought it was just an infection, and we treated with antibiotics for 3 weeks and[eventually] it went away. And sort of miraculously he was in remission and is still in remission, 9 years later.

And then when we treated Emily. She was at a 106-degree fever over three days, and there was no infection.

Ive told this story before. My daughter has rheumatoid arthritis, and I had been president of the Clinical Immunologists Society from 2009 to 2010, and the first good drug for juvenile rheumatoid arthritisthat came out. I was invited to give the Japanese scientist Tadamitsu Kishimoto the presidential award for inventing the drug.

Then in 2012, Emily Whitehead was literally dying from CRS, she had multiple organ failures. And her labs came back and IL-6 levels were 1000x normal. It turns out the drug I was looking at for my daughter, it blocks IL-6 levels. I called the physician and I said, listen theres something actionable here, since its in your formulary to give it to her off-label.

And she gave her the appropriate dose for rheumatoid arthritis. It was miraculous. She woke up very rapidly.

Now its co-labeled. When the FDA approvedKymriah, it was co-labeled. It kind of saved the field.

How were you feeling during this time? Did you have any idea what was happening to her?

No, not until we got the cytokine levels, and then it was really clear. The cytokine levels go up and it exactly coincided. Then we retroactively checked out adults and they had adverse reactions and it easy to see. We hadnt been on the lookout because it wasnt in our mouse models.

And it appeared with those who got cured. Its one of the first on-target toxicities seen in cancer, a toxicity that happens when you get better. All the toxicities from chemotherapy are off-target: like leukopenia or hair loss.

I had a physician who had a fever of 106, I saw him on a fever when he was starting to get CRS. When the nurse came in and it said 106, they thought the thermometer must be broken. On Monday, I saw him, and said how are you feeling and he said fine. And I looked at the thermometer and histemperature was still 102.

People will willingly tolerate on-target toxicity thats very different from chemotherapy if they know it helps get them better. Thats a new principle in cancer therapy.

You had these early CART results almost at the same time that Doudna publishes the first CRISPR papers, then still in bacteria. When did you first start thinking about combining the two?

Yeah, it was published inSciencein 2012 and thats when Emily Whitehead got treated. Its an amazing thing.

Thats something so orthogonal. You think how in the heck can that ever benefit CART cells? but my lab had done the first edited cells in patients, published in 2012. And we used zinc-fingered nucleases, which were the predecessors to CRISPR. It knocked out one gene at a time, but we showed it was safe.

I was already into gene editing because it could make T cells resistant to HIV. So it was pretty obvious that there were candidates in T cells that you can knock out. And almost every lab started working on some with CRISPR, cause it was much easier.

We were the first to get full approval by the FDA, so we worked on it from 2012, had all the preclinical data by 2016, and then it takes a while to develop a lot of new assays for this as we were very cautious to optimize safety and it took longer than we wanted, but in the end, we learned a tremendous amount.

So what did we learn?

First of all our patients had advanced metastatic cancer and had had a lot of chemotherapy. The first patient had had 3 bone marrow transplants.

One thing is feasibility: could you really do all the complex engineering? So we found out we could. feasibility was passed.

Another was the fact that cas9 came out of bacteria, forms of strep and staph. Everyone has pre-existing immunity to Cas9 and we had experience from the first trial with Sangamo[with zinc-finger nucleases] where some patients had a very high fever. In that case, we had used adenoviruses, and it turned out our patients had very high levels of baseline immune response to adenoviruses, so we were worried that would happen with CRISPR, and it did not happen.

It did not have any toxicity. If it had, it would have really set the field back. If there was animmune response to cas9 and CRISPR, there couldve been a real barrier to the field.

And then, the cells survived in the patients. The furthest on, it was 9 months. The cells had a very high level of survival. In the previous trials, the cells survived less than 7 days. In our case, the half-life was 85 days. We dont know the mechanism yet.

And we found very big precision in the molecular scissors, and that was a good thing for the field. You could cut 3 different genes on 3 different chromosomes and have such high fidelity.

It [CRISPR] is living up to the hype. Its going to fix all these diseases.

Whats the potential in CAR-T, specifically?

Well theres many many genes that you can add. There are many genes that knocking outwill make the cells work better. We started with the cell receptor. There are many, I think, academics and biotechs doing this now and it should make the cells more potent and less toxic.

And more broadly, what else are you looking at for the future of CART? The week before your paper, there were the results from MD Anderson on natural killer cells.

Different cell types, natural killer cells, stem cells putting CAR molecules into stem cells, macrophages. One of my graduate students started a company to do CAR macrophages and macrophages actually eat tumor cells, as opposed to T cells that punch holes in them.

There will be different cell types and there will be many more ways to edit cells. The prime editing and base editing. All different new variations.

Youve talked about how people used to think the immuno-oncology, if it ever worked, would nevertheless be a boutique treatment. Despite all the advancements, Novartis and Gilead still have not met the sales they once hoped to grab from their CART treatments. Are you confident CART will ever be widely accessible?

Oh yeah, Novartis sales are going up. They had a hiccup launching.

Back in 96 or 97, when Genentech launched Herceptin, their commercial antibody, they couldnt meet the demand either and then they scaled up and learned how to do better cultures. So right now Novartis is using tech invented in my lab in the 1990s culture tech thats complex and requires a lot of labor, so the most expensive part is human labor. A lot can be made robotic. The scale problem will be much easier.

Thats an engineering problem that will become a thing of the past. The manufacturing problem will get a lot cheaper. Here in the US, we have a huge problem with how drugs are priced. We have a problem with pricing. Thats a political issue.

But in cell therapy, its just kind of the growth things you see in a new industry. Itll get worked out.

This article has been updated to reflect that Jim Riley conducted work on CAR in HIV.

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Carl June on CRISPR, CART and how the Vietnam War dropped him into medicine - Endpoints News

DUBLIN, Feb. 14, 2020 /PRNewswire/ -- The "Global In-Silico Drug Discovery Market: Focus on Products, Technologies, Workflow, End Users, Country Data (17 Countries), and Competitive Landscape - Analysis and Forecast, 2018-2029" report has been added to ResearchAndMarkets.com's offering.

The in-silico drug discovery industry analysis projects the market to grow at a significant CAGR of 12.92% during the forecast period, 2019-2029. The in-silico drug discovery market generated $2,094.5 million in revenue in 2018, in terms of value.

The global in-silico drug discovery market growth has been primarily attributed to the major drivers in this market such as an emphasis on the reduction in medical errors and readmission rates, growth in the biomarker identification market and advancements in In-silico drug discovery techniques, and computational technological advancements in the field of computational biology.

However, there are significant challenges that are restraining the market growth. These challenges include the high cost of methods and expensive procedures and their applications in medical treatments.

Expert Quote

North America is the leading contributor to the in-silico drug discovery market and contributed approximately 41.65% to the global market value in 2018. This region is anticipated to grow at a significant CAGR during the forecast period 2019-2029 and continue dominating the global market in 2029. However, the Asia-Pacific region is expected to grow at the highest CAGR of 13.29% during the forecast period. In addition, the region of Europe also contributed a significant share of 28.40% to the global market in 2018.

Scope of the Market Intelligence

The in-silico drug discovery research provides a holistic view of the market in terms of various factors influencing it, including regulatory reforms, and technological advancements.

The scope of this report is centered upon conducting a detailed study of the products and manufacturers allied with the service market. In addition, the study also includes exhaustive information on the unmet needs, perception of the new products, competitive landscape, market share of leading manufacturers, the growth potential of each underlying sub-segment, and company, as well as other vital information with respect to the global in-silico drug discovery market.

Key Companies in the Market

The key manufacturers who have been contributing significantly to the global in-silico drug discovery market include Albany Molecular Research Inc., Certara USA, Inc., Charles River, Chemical Computing Group ULC, Collaborative Drug Discovery Inc., Dassault System (Biovia), Evotec A.G., GVK Biosciences Private Limited, ICAGEN, INC., Novo Informatics Pvt. Ltd., Numerate Inc., PerkinElmer Inc, Schrdinger, LLC, Selvita, Simulation Plus, and WuXi AppTec, among others.

Key Questions Answered in the Report

Key Topics Covered

1 Product Definition1.1 Inclusion and Exclusion

2 Research Scope2.1 Scope of the Study2.2 Key Questions Answered in the Report

3 Research Methodology3.1 Global In-Silico Drug Discovery Market: Research Methodology3.2 Primary Data Sources3.3 Secondary Data Sources3.4 Market Estimation Model

4 Industry Analysis4.1 Regulatory Framework4.1.1 Regulatory Framework in North America4.1.2 Regulatory Framework in Europe4.1.3 Regulatory Framework in Asia-Pacific

5 Competitive Landscape5.1 Mergers and Acquisitions5.2 Product Launches and Product Updates5.3 Synergistic Activities5.4 Business Expansion Activities and Others5.5 Market Share Analysis

6 Market Dynamics6.1 Overview6.2 Impact Analysis6.3 Market Drivers6.3.1 Emphasis on Reduction in Medical Errors and Readmission Rates6.3.2 Growth in the Biomarker Identification Market and Advancements in In-Silico Drug Discovery Techniques6.3.3 Technological Advancements in the Field of Computational Biology6.4 Market Restraints6.4.1 Lack of High Complexity Testing Centers6.4.2 Expensive Procedures and Their Applications in Medical Treatments6.4.3 High Capital Requirement Hampering the Expansion of Global Reach6.5 Market Opportunities6.5.1 Massive Scope for Adoption of In-Silico Drug Discovery in Developing Nations6.5.2 Integration of Blockchain Technology in Interoperability6.5.3 Collaborations With Precision Medicine Providers

7 In-Silico Drug Discovery: Overview7.1 Introduction7.2 Market Availability for In-Silico Drug Discovery7.3 In-Silico Drug Discovery Market Technology Trends

8 Global In-Silico Drug Discovery Market (by Workflow)8.1 Overview8.2 Discovery8.2.1 Target Identification8.2.1.1 Bioinformatics8.2.1.2 Reverse Docking8.2.1.3 Protein Structure Prediction8.2.2 Target Validation8.2.3 Lead Discovery8.2.3.1 Library Design8.2.3.2 Pharmacophore8.3 Pre-Clinical Tests8.4 Clinical Trials

9 Global In-Silico Drug Discovery Market (by Product)9.1 Software9.2 Software as-a-Service (Cloud)9.3 Consultancy as-a-Service

10 Global In-Silico Drug Discovery Market (by Software Type)10.1 Molecular Modeling and de Novo Drug Design Software10.2 Pharmacophore Modeling Software

11 Global In-Silico Drug Discovery Market (by End-user)11.1 Contract Research Organizations11.2 Pharmaceutical Industry11.3 Academic and Research Institutes11.4 Other End-users (Hospitals and Other Care Facilities)

12 Global In-Silico Drug Discovery Market, by Region12.1 Overview12.2 North America12.2.1 U.S.12.2.2 Canada12.3 Europe12.3.1 Germany12.3.2 France12.3.3 U.K.12.3.4 Italy12.3.5 Spain12.3.6 Russia12.3.7 Rest-of-Europe12.4 Asia-Pacific12.4.1 China12.4.2 Japan12.4.3 Australia12.4.4 India12.4.5 South Korea12.4.6 Rest-of-APAC12.5 Latin America12.5.1 Brazil12.5.2 Mexico12.6 Rest-of-the-World

13 Company Profiles13.1 Overview13.2 Albany Molecular Research Inc.13.2.1 Company Overview13.2.2 Role of Albany Molecular Research in the Global In-Silico Drug Discovery Market13.2.3 SWOT Analysis13.3 Certara USA Inc.13.4 Charles River13.5 Chemical Computing Group ULC13.6 Collaborative Drug Discovery Inc.13.7 Dassault System (Biovia)13.8 Evotec AG13.9 GVK Biosciences Private Limited13.10 ICAGEN Inc.13.11 Novo Informatics Pvt. Ltd.13.12 Numerate Inc.13.13 PerkinElmer Inc.13.14 Schrdinger LLC13.15 Selvita13.16 Simulation Plus13.17 WuXi AppTec13.18 e-therapeutics plc (Snapshot)

For more information about this report visit https://www.researchandmarkets.com/r/2rpum3

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Global In-Silico Drug Discovery Industry Forecasts to 2029 - Integration of Blockchain Technology in Interoperability Presents Massive Opportunities -...

Human urinary bladder cancer is one of the most common cancers worldwide with the mortality rate of approximately 165,000 people annually. The modulation of extracellular matrix is a crucial event in the metastatic spread, among others in angiogenesis. It is initiated and prolonged by the cascade of matrix metalloproteinases. MMP-14 and MMP-15 are associated with a high degree of malignancy, aggressiveness, and survival prognosis by the activation of other matrix metalloproteinases (MMPs). This study was aimed at evaluating the expression and the activity of selected transmembrane metalloproteinases at different stages of human urinary bladder cancer.

Western blot and enzyme linked immunosorbent assay (ELISA) method were used to evaluate the expression and content of MMPs and TIMP-1. The activity of studied enzymes was determined with fluorometric method.

Both transmembrane metalloproteinases are found in healthy or cancerous tissue in high molecular complexes of human urinary bladder. MMP-14 dominates over MMP-15, particularly in high-grade urinary bladder cancer. Their contents significantly change with the grade of bladder tumor. The amount of MMP-14 increases with increasing grade of tumor. MMP-15 content decreases in high-grade bladder cancer. With increasing grade of urinary bladder cancer their actual activity (per kg of total protein content) is varying in different ways. In all examined tissues, the specific activity of MMP-15 (per kg of the enzyme content) is much higher in comparison to MMP-14. Human urinary bladder cancer contains higher TIMP-1 amounts than control tissue but with the decrease with an increase in tumor grade.

Comparison of investigated enzymes' activity and the inhibitor content suggests it opposite effects, higher suppression of MMP-14 than MMP-15 activity in low-grade bladder cancer and reverse TIMP-1 action in high-grade cancer. The MMP-14 activity determination in urinary bladder cancer tissue may be used as a predictor of a risk of metastasis.

Medicine. 2020 Feb [Epub]

Jacek Kudelski, Grzegorz Mynarczyk, Barbara Darewicz, Marta Bruczko-Goralewska, Lech Romanowicz

Department of Urology, Medical University of Biaystok, Poland., Department of Medical Biochemistry.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/32049862

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Dominative role of MMP-14 over MMP-15 in human urinary bladder carcinoma on the basis of its enhanced specific activity. - UroToday

NEW YORK, Jan. 16, 2020 (GLOBE NEWSWIRE) -- Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative targeted medicines and artificial intelligence to find, fight and follow cancer, today announced that an abstract highlighting data from its PSMA AI program has been selected for a moderated poster presentation at the 2020 Society for Nuclear and Molecular Medicine (SNMMI) Mid-Winter Meeting, which will be held from January 23 25, 2020 in Tampa, FL.

Date & Time:January 23, 2020 from 12:15 p.m. to 1:15 p.m. Eastern TimeTitle:Deep Learning-Enabled Automated Hotspot Detection from 18F-DCFPyL (PyL-PSMA) PET/CT in Metastatic Prostate Cancer

About PyL for PET Imaging of Prostate CancerPyL (also known as 18F-DCFPyL) is a fluorinated PSMA-targeted positron emission tomography (PET) imaging agent that enables visualization of both bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer.

About PROGENICS

Progenics is an oncology company focused on the development and commercialization of innovative targeted medicines and artificial intelligence to find, fight and follow cancer, including: therapeutic agents designed to treat cancer (AZEDRA, 1095, and PSMA TTC); prostate-specific membrane antigen (PSMA) targeted imaging agents for prostate cancer (PyL and 1404); and imaging analysis technology (aBSI and PSMA AI). Progenics has three commercial products, AZEDRA, for the treatment of patients with unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma (rare neuroendocrine tumors of neural crest origin) who require systemic anticancer therapy; and oral and subcutaneous formulations of RELISTOR (methylnaltrexone bromide) for the treatment of opioid-induced constipation, which are partnered with Bausch Health Companies Inc.

Forward Looking StatementsThis press release contains projections and other forward-looking statements regarding future events. Statements contained in this communication that refer to Progenics estimated or anticipated future results or other non-historical facts are forward-looking statements that reflect Progenics current perspective of existing trends and information as of the date of this communication and include statements regarding Progenics strategic and operational plans and delivering value for shareholders. Forward looking statements generally will be accompanied by words such as anticipate, believe, plan, could, should, estimate, expect, forecast, outlook, guidance, intend, may, might, will, possible, potential, predict, project, or other similar words, phrases or expressions. Such statements are predictions only and are subject to risks and uncertainties that could cause actual events or results to differ materially. These risks and uncertainties include, among others: risks associated with the proposed merger transaction with Lantheus Holdings, Inc.; market acceptance for approved products; the risk that the commercial launch of AZEDRA may not meet revenue and income expectations; the cost, timing and unpredictability of results of clinical trials and other development activities and collaborations; the unpredictability of the duration and results of regulatory review of New Drug Applications (NDA) and Investigational NDAs; the inherent uncertainty of outcomes in the intellectual property disputes such as the dispute with the University of Heidelberg regarding PSMA-617; our ability to successfully develop and commercialize products that incorporate licensed intellectual property; the effectiveness of the efforts of our partners to market and sell products on which we collaborate and the royalty revenue generated thereby; generic and other competition; the possible impairment of, inability to obtain and costs of obtaining intellectual property rights; possible product safety or efficacy concerns, general business, financial, regulatory and accounting matters, litigation and other risks; and risks related to changes in the composition of our Board of Directors following the delivery of shareholder consents in response to the recent consent solicitation conducted by one of our shareholders. More information concerning Progenics and such risks and uncertainties is available on its website, and in its press releases and reports it files with the Securities and Exchange Commission (the SEC), including those risk factors included in its Annual Report on Form 10-K for the year ended December 31, 2018, as updated in its subsequent Quarterly Reports on Form 10-Q. Progenics is providing the information in this press release as of its date and, except as expressly required by law, Progenics disclaims any intent or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or circumstances or otherwise.

Additional information concerning Progenics and its business may be available in press releases or other public announcements and public filings made after this press release. For more information, please visit http://www.progenics.com. Information on or accessed through our website or social media sites is not included in the companys SEC filings.

ContactMelissa DownsInvestor Relations(646) 975-2533mdowns@progenics.com

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Progenics Pharmaceuticals Announces Presentation at the 2020 SNMMI Mid-Winter Meeting - BioSpace

Food is more than the energy that fuels our bodies it is preventive medicine. Maybe not a cheesy chimichanga, but the type of food that is loaded with vitamins and proteins can maximize the benefits to the human body.

We need to look at the functional properties of food more closely so we can achieve the desired outcome, said Justin Siegel, associate professor of chemistry, biochemistry and molecular medicine, and faculty director for the Innovation Institute for Food and Health. Instead of focusing on the quantity of food which is a legitimate long-term concern globally lets hone in on creating quality food that possesses more active nutritional ingredients that deliver greater health benefits with every serving.

Siegel has a vision to transform the greater Sacramento region into the incubator pipeline for food science innovations. The initiative, dubbed Food Valley, would accelerate the commercialization of game-changing ideas across the food system by tapping into research, industry and policy. It would also prepare tomorrows food innovators and entrepreneurs through experiential learning programs.

Food Valley aims to patent its food innovations through developing technologies. These concepts can be grown into companies and potentially be a launchpad for Aggie entrepreneurs.

Siegel became interested in biotechnology as a kid. More recently, he thought about the possibilities of using biotech to disrupt the food systems industry. He co-founded PVP Biologics, a food biotech company, in 2016. PVP created a pill called KumaMax, which could help those who have celiac disease. KumaMax is currently in clinical trials, awaiting FDA approval.

Food Valley is about letting people experience freedom in what they are able to eat especially as it pertains to food allergies and restrictions, Siegel said. With modern technology we can both see the exact molecules that make up our food and manipulate those molecules to change how they interact with someones body.

No centralized hub for food innovations exists yet. Siegel said he believes UCDavis has the right ingredients to emerge as the leader.

Twenty years ago, this was science fiction, he said. Now we can do things we never thought possible. There is going to be a hub for food innovation, and UCDavis should be the place it happens.

This is one of several Big Ideas, forward-thinking, interdisciplinary programs and projects that will build upon the strengths of UCDavis to positively impact the world for generations to come. Learn more at bigideas.ucdavis.edu.

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The Future of Food - UC Davis

06 September 2019, Berlin: After a group music therapy session in a dementia residential community ... [+] in Berlin-Neuklln, which is looked after by the Unionhilfswerk, one resident holds hands. In Germany, the number of people suffering from dementia is increasing. Although the sick forget more and more, music can reawaken certain memories - at least for a moment. (to dpa "Dit one does not forget" - with music memories awaken) Photo: Christoph Soeder/dpa (Photo by Christoph Soeder/picture alliance via Getty Images)

Alzheimers is a devastating diagnosis for people suffering from the disease, as well as their families, but a group of researchers feels that they are one step closer to finding a cure.

Alzheimer's disease (AD) affects about 5.7 million people in the US and is the leading cause of age-related dementia today. Many people suffering from AD face a myriad of challenges including the lack of effective treatments, reliable biomarkers, or preventive strategies. Unfortunately, several promising drug candidates in the past have failed in clinical trials so researchers are still searching for new preventions or therapies to combat the development of AD. But there seems to be hope with a new vaccine that may proceed to clinical trials after successful animal testing.

A new paper in the journalAlzheimer's Research & Therapyis opening the door for further research in 2020, with medical researchers at the Institute for Molecular Medicine and University of California, Irvine (UCI) working with a successful vaccine formulated on adjuvants(1) developed by Flinders University Professor Nikolai Petrovsky in South Australia.

The causes of AD, in part, are believed to be tied to the role two proteins in the brain;

It is these two proteins that the US-led research team is looking to develop effective immunotherapy for via a new vaccine to remove brain plaques and tau protein tangles.

As explained in the research teams report, Alzheimer disease (AD) is characterised by the accumulation of beta-amyloid (A) plaques and neurofibrillary tangles composed of hyperphosphorylated(2) tau, which together lead to neurodegeneration and cognitive decline, continuing that, Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either A or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. The researchers contend that combinatorial therapies that concurrently target both A and tau might be needed for effective disease modification.

The research teams claims that recent success in their tests with mice supports progression to human trials in years to come, sparking hope in he field. "Our approach is looking to cover all bases and get past previous roadblocks in finding a therapy to slow the accumulation of A/tau molecules and delay AD progression in a the rising number of people around the world," says Professor Petrovsky.

However, one downside of the potential vaccine is thatit could not currently be used as a preventive measure in healthy subjects due to the need for frequent (monthly) administration of high concentrations of immunotherapeutic drugs, which are a class of drugs targeting the immune system to either kickstart or suppress immune function.

However, if future human trials are successful, the new paper concludes that the new combined vaccination approach could potentially be used to induce strong immune responses to both of the hallmark pathologies of AD in a broad population base of vaccinated subjects with high MHC (major histocompatibility complex(3)) class II gene polymorphisms, stating that, This synergistic model suggests that combinatorial/multi-target therapies directed at the accumulation of both amyloid and tau pathologies may be more effective in the treatment of AD than previously tested unimodal approaches.

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We May Be One Step Closer To A Vaccine Against Alzheimers Disease - Forbes