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Scooped by Dr. Stefan Gruenwald!

Immune Engineering to Approach a Cure for Cancer

Immune Engineering to Approach a Cure for Cancer | Amazing Science |
Genetically engineered immune cells are saving the lives of cancer patients. That may be just the start.


Cellectis began developing the treatment in 2011 after doctors in New York and Philadelphia reported that they’d found a way to gain control over T cells, the so-called killer cells of the immune system. They had shown that they could take T cells from a person’s bloodstream and, using a virus, add new DNA instructions to aim them at the type of blood cell that goes awry in leukemia. The technique has now been tested in more than 300 patients, with spectacular results, often resulting in complete remission. A dozen drug firms and biotechnology companies are now working to bring such a treatment to market.


The search to expand immune therapy now involves not only the world’s largest drug companies but also tech firms. Sharp says that last year Google held two summits at MIT of top immune oncologists and bioengineers to determine what parts of the problem could be “Googlified.” Attendees say the search giant paid special attention to new research techniques that fingerprint cells from a tumor biopsy in rapid-fire fashion. These methods might generate big data about what immune system cells are actually doing inside a tumor, and new clues about how to influence them. So far, Google’s life science unit, named Verily, hasn’t revealed its plans in cancer immunotherapy. But in New York’s Union Square, I met Jeffrey Hammerbacher, a former Facebook employee who now runs a lab that is part of Mount Sinai, the hospital and medical school. With 12 programmers in a light-soaked loft—the nearest thing to blood and guts is a photo of an exhausted surgeon on the wall—he’s also spending time on T cells. He’s developing software to interpret the DNA sequence in a patient’s cancer and predict from it how to goose the response of killer T cells.


A clinical trial by Mount Sinai should start this year. The patients receive a dose of abnormal protein fragments that Hammerbacher’s software predicts will train T cells to attack the cancer. “What was fun was that what we submitted to the [U.S. Food and Drug Administration] was not a molecule but an algorithm,” he says. “It might be one of the first times the output of a program is the therapy.”


In January, Juno Therapeutics (see “Biotech’s Coming Cancer Cure”) paid $125 million to acquire AbVitro, a Boston-area company that specializes in sequencing the DNA inside single T cells. Now Juno is trying to locate T cells that are active inside cancers and study their receptors. Juno’s chief scientist, Hyam Levitsky, says an experiment that used to take seven months now takes seven days. And data is piling up: an average experiment generates 100 gigabytes of information. “A lot of what is happening is technology-driven,” he says. “The questions have been there for a while, but there was no way to get at the answers. Now we’re visualizing them with new technology in ways we never could before.”  


In March Pfizer appointed John Lin to head its San Francisco biotech unit, which develops cancer drugs and recently started making engineered T cells. He says the company had been negotiating with Cellectis well before the news of Layla’s treatment and that no one there was even aware the girl had been treated before it hit the news. “The publicity was a big surprise,” he says.


Lin says years of scientific work have finally resulted in a level of mastery that makes therapeutic products seem practical. He thinks the treatments will go beyond leukemia, and beyond cancer. “We think that this fundamental principle, engineering human cells, could have broad implications,” he says, “and the immune system will be the most convenient vehicle for it, because they can move and migrate and play such important roles.”


Researchers are already working on autoimmune disorders, like diabetes, multiple sclerosis, and lupus. Infectious disease is also in the sights of T-cell engineers. Edward Berger, a virologist at the National Institutes of Health who helped discover how HIV enters human cells, thinks it may be possible to permanently keep the virus in check, a so-called “functional cure.” In February, he says, he will start giving monkeys T cells genetically programmed to find and destroy any cell in which the simian version of HIV is replicating.

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Wearable Artificial Kidney Completes First Clinical Trial, Could Free People From Dialysis

Wearable Artificial Kidney Completes First Clinical Trial, Could Free People From Dialysis | Amazing Science |
Positive results from the first clinical trial on a wearable artificial kidney may soon replace dialysis.For anyone suffering from kidney disease, their only course of treatment is hemodialysis—a costly, time consuming, and cumbersome method that requires a patient being hooked up to a machine. Through the years, researchers have sought to find a wearable and portable alternative that could allow for more mobility and more sessions, but minus the hassle.

Now, the results of an FDA-approved human trial of a wearable artificial kidney have just been published. The device is essentially a miniature version of the traditional, stationary hemodialysis machine, and it could one day change current methods of dialysis.

Russell R. Roberts, Jr.'s curator insight, June 18, 12:55 AM
This development could almost be called a medical miracle. An artificial kidney could allow an almost "normal" life for thousands of dialysis patients.  Medical research dollars well spent.
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Ultrasound Opens the Blood-Brain Barrier to Promising Drugs in Brain Cancer

Ultrasound Opens the Blood-Brain Barrier to Promising Drugs in Brain Cancer | Amazing Science |

The protective sheath surrounding the brain’s blood supply—known as the blood-brain barrier—is a safeguard against nasty germs and toxins. But it also prevents existing drugs that could potentially be used to treat brain cancer or Alzheimer’s disease from reaching the brain. That’s why scientists want to unchain the gates of this barrier. Now a new study shows it’s been done in cancer patients.


Alexandre Carpentier, a neurosurgeon at the Pitié-Salpêtrière Hospital in Paris, used ultrasound to open the blood-brain barrier in patients with recurrent glioblastoma—the most common and deadly tumor originating in the adult brain—allowing for delivery of chemotherapy that would otherwise reach the tumor in miniscule amounts. The preliminary results of the early phase clinical trial were reported Wednesday in Science Translational Medicine.


The procedure works by first injecting microbubbles into the bloodstream, and then using a device implanted near patients’ tumors to send ultrasonic soundwaves into the brain, exciting the bubbles. The physical pressure of the bubbles pushing on the cells temporarily opens the blood brain barrier, letting an injected drug cross into the brain.


“People for years have been trying to open the blood-brain barrier,” said Neal Kassell, founder of the Focused Ultrasound Foundation. The device, called SonoCloud, was implanted and used on 15 patients during monthly chemotherapy administration with no ill effects after six months.


Although this is the first published study using ultrasound to open the blood-brain barrier in humans, it is not the first study to hit the news. In November, a team at the Sunnybrook Health Sciences Centre in Toronto announced the start of a clinical trial to open the blood-brain barrier using ultrasound in a single brain cancer patient. Carpentier’s trial, on the other hand, began in July 2014, and Kassell said the French study “is the first time they’ve shown the safety of repetitively opening the blood-brain barrier in humans.” Both clinical trials are ongoing.


The Sunnybrook trial used a focused ultrasound device, which is good for pinpointing localized cancers. In contrast, SonoCloud emits ultrasound more diffusely, which is useful for glioblastomas that blend into surrounding brain tissue. “It seems a little more aggressive to implant something,” Carpentier said, but the wider-ranging ultrasound opens a larger swath of the blood-brain barrier. This enables chemotherapy drugs to reach cancer cells around the periphery of the main tumor, hopefully reducing the chance that the cancer will grow back.

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First teleoperated endolumenal robot from secretive startup Auris cleared for use by FDA

First teleoperated endolumenal robot from secretive startup Auris cleared for use by FDA | Amazing Science |

Teleoperated endolumenal bot can navigate inside the body, image and treat conditions without making incisions.


The U.S. Food and Drug Administration (FDA) has just approved the first medical robot from Auris Surgical, a stealthy startup led by the co-founder of industry leader Intuitive Surgical, makers of the widely-used da Vinci robot.


The teleoperated ARES robot (the acronym stands for Auris Robotic Endoscopy System), was cleared by the FDA at the end of May, and could now be used for diagnosing and treating patients.


Auris, which describes itself only as a “technology company based in Silicon Valley,” was previously thought to be working on a robotic microsurgical system designed to remove cataracts, and the company has in fact filed several patent applications along those lines.


However, an investigation by IEEE Spectrum suggests that the company has greater ambitions, including, according to current and former employees, “building the next generation of surgical robots… capable of expanding the applicability of robotics to a broad spectrum of medical procedures.”


A close reading of recent patent applications filed by Auris scientists shows that the company is focusing on so-called endolumenal (or endoluminal) surgery. This involves surgeons introducing flexible robots via the body’s natural openings (the mouth in particular), to address conditions of the throat, lungs and gastrointestinal system. IEEE Spectrum can reveal that Auris has already carried out at least one successful human trial of such a robot, outside the United States.


Because endolumenal surgery does not involve large incisions or (usually) general anesthesia, it benefits fragile patients who cannot withstand the trauma of normal surgery. The Society for American Gastrointestinal and Endoscopic Surgeons estimates that effective endolumenal therapies for obesity and reflux diseases alone could help more than 1 million patients a year in the United States.

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Stem cell gene Oct4 helps to prevent heart attack, stroke, and counteracts aging

Stem cell gene Oct4 helps to prevent heart attack, stroke, and counteracts aging | Amazing Science |

University of Virginia School of Medicine have discovered that a gene called Oct4 — which scientific dogma insists is inactive in adults — actually plays a vital role in preventing ruptured atherosclerotic plaques inside blood vessels, the underlying cause of most heart attacks and strokes.


The researchers found that Oct4 controls the conversion of smooth muscle cells into protective fibrous “caps” inside plaques, making the plaques less likely to rupture. They also discovered that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques. In addition, the researchers believe it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a way to reduce the incidence of heart attacks or stroke.


The researchers are also currently testing Oct4′s possible role in repairing cellular damage and healing wounds, which would make it useful for regenerative medicine.


Oct4 is one of the “stem cell pluripotency factors” described by Shinya Yamanaka, PhD, of Kyoto University, for which he received the 2012 Nobel Prize. His lab and many others have shown that artificial over-expression of Oct4 within somatic cells grown in a lab dish is essential for reprogramming these cells into induced pluripotential stem cells, which can then develop into any cell type in the body or even an entire organism.


“Finding a way to reactivate this pathway may have profound implications for health and aging,” said researcher Gary K. Owens, director of UVA’s Robert M. Berne Cardiovascular Research Center. “This could impact many human diseases and the field of regenerative medicine. [It may also] end up being the ‘fountain-of-youth gene,’ a way to revitalize old and worn-out cells.”

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Bionic Spinal Cord Lets You Move Robotic Limbs With Power of Thought

Bionic Spinal Cord Lets You Move Robotic Limbs With Power of Thought | Amazing Science |

Australian researchers have created a “bionic spinal cord.” They claim that this device could give paralyzed people significant hope of walking again. And if that’s not enough, it could do it utilizing the power of thought and without the necessity of open brain surgery.


A research team from the Vascular Bionics Laboratory at the University of Melbourne developed the novel neural-recording device, which both eschews invasive surgery and decreases the risks of a blood-brain barrier breach by being implanted into the brain’s blood vessels.


Developed under DARPA’s Reliable Neural-Interface Technology (RE-NET) program, the Stentrode can potentially safely expand the use of brain-machine interfaces (BMIs) in the treatment of physical disabilities and neurological disorders.


The researchers describe their “proof-of-concept results” which come from a study conducted on sheep, demonstrating high-fidelity measurements taken from the region of the brain responsible for controlling voluntary movement (called the motor cortex) with the use of the novel device which, as it happens, is just about the size of a paperclip.


Notably, the device records neural activity that has been shown in pre-clinical trials to move limbs through an exoskeleton.


The team, led by neurologist Thomas Oxley, M.D., published their study in an article in the journal Nature Biotechnology.

Via Mariaschnee
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Using Natural Killer Cells within us to Fight Cancer

Using Natural Killer Cells within us to Fight Cancer | Amazing Science |

Our bodies are constantly and successfully fighting off the development of cells that lead to tumors - but when there is disruption to this process cancer is free to develop.

Walter and Eliza Hall Institute researchers, led by Dr Sandra Nicholson and Dr Nicholas Huntington, together with colleagues from the Queensland Institute of Medical Research, are investigating ways to 'switch on' our Natural Killer (NK) cells.


Natural Killer cells exist to detect and then destroy any deviant cells in our bodies before those cells go on to develop into tumors or before infection spreads, Dr Nicholson said. "Natural Killer cells are a key part of our immune system that locate other cells posing a danger to health either because they are infected or because they are becoming a cancer cell," she said. However, it is known that abnormal cells sometimes escape the immune system and develop into a cancer.


The researchers identified a protein 'brake' within Natural Killer cells that controls their ability to destroy their target tumor cells.

In their paper published today in Nature Immunology, they showed that when the brake was removed in an experimental model, the NK cells were better able to protect the body against metastatic melanoma.


Natural Killer cells rely on a growth factor called Interleukin 15 (IL15) to activate. Dr Nicholson and Dr Huntington's research has shown that an inhibitor protein made inside the Natural Killer cells limits the ability of the NK cell to respond to IL15 and therefore kill cancer cells. By identifying for the first time how this protein inhibits NK cell responses, they now hope that a drug can be developed that will improve the NK cells' response to this growth factor and help patients fight cancer with their own immune system. "This is about learning how to activate the NK cells of the individual patient and boost their immune system to tackle the disease," Dr Huntington said.

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Biochemistry and Cell Biology of Tau in Neurofibrillary Degeneration

Biochemistry and Cell Biology of Tau in Neurofibrillary Degeneration | Amazing Science |

The tau protein is a subunit of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications (phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming β structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.

Via Krishan Maggon
Krishan Maggon 's curator insight, May 18, 2:01 AM
Cold Spring Harb Perspect Med. 2012 Jul; 2(7): a006247. 
doi: 10.1101/cshperspect.a006247 PMCID: PMC3385935 

Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration 

Eva-Maria Mandelkow and Eckhard Mandelkow

Image   Visualization of Tau and kinesin bound to microtubules.
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Gamma-retroviruses preferentially integrate near cancer-associated genes

Gamma-retroviruses preferentially integrate near cancer-associated genes | Amazing Science |

Identifying the sites where gamma-retroviruses commonly insert into the genome may help to identify genes associated with specific cancer types, according to a study published April 20, 2016 in the open-access journal PLOS ONE by Kathryn Gilroy at the University of Glasgow, UK, and colleagues.


Gamma-retroviruses, such as feline leukaemia virus, tend to cause mutations when they insert into a host’s genome, and have been used as a tool to discover genes associated with cancer. However, this discovery process can be time consuming, requiring the collection of multiple tumors from animals and comparative genomic analyses. The authors of the present study sought to investigate the pattern of gamma-retrovirus insertion using deep sequencing to analyse common insertion sites for feline leukaemia virus in cell culture. The study was also expanded to analyze published genome insertion profiles of other gamma-retroviruses.


The authors found that the gamma-retroviruses preferentially inserted into cancer-driving genes, regardless of transcription levels, in a cell type-specific manner. This authors suggest that gamma-retrovirus integration profiling in vitro may be a tool to identify potential therapeutic target genes in different human cancer types.

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Penn Bioengineers Show Why Lab-made Stem Cells Might Fail: Errors in DNA Folding

Penn Bioengineers Show Why Lab-made Stem Cells Might Fail: Errors in DNA Folding | Amazing Science |

Induced pluripotent stem cells hold promise for regenerative medicine because they can, in theory, turn into any type of tissue and because they are made from a patient’s own adult cells, guaranteeing compatibility. However, the technique that turns adult cells into these iPS cells is not foolproof; after reverting to their pluripotent state, these cells don’t always correctly differentiate back into adult cells. 


Researchers from the University of Pennsylvania have now discovered one of the reasons why: the reversion process does not always fully capture the way a cell’s genome is folded up inside its nucleus. This folding configuration directly influences gene expression and therefore the functionality of the cell.


The new study shows that current techniques might not produce iPS cells that are equivalent to the pluripotent stem cells found in embryos, as some clones retain folding patterns that partially resemble those found in the adult cells from which they are made.  


Led by Jennifer Phillips-Cremins, assistant professor in the School of Engineering and Applied Science’s Department of Bioengineering, and Jonathan Beagan, a graduate student in her lab, the study, published in the journal Cell Stem Cell, also suggests ways of minimizing these folding errors.


Though techniques for reverting adult cells into iPS cells have existed for a decade and avoid the issues surrounding the use of embryonic stem cells that have stymied research into regenerative medicine, clinical investigations of these cells have been cautious and slow. IPS cells can fail to correctly differentiate into the desired tissue. Moreover, there are also concerns that the resulting tissue could have unforeseen genetic abnormalities or could become cancerous.


Even outside the clinical applications, many researchers are interested in iPS cells as a way of generating a “disease in a dish.” Rather than taking a tissue sample from a patient with a genetic disorder, which is especially challenging when the affected organ is the brain, researchers could use iPS cells derived from that patient’s skin cells to grow model organs as needed. Observing the development of those tissues could provide clues to the progression of the disease, as well as serve as ideal test-beds for treatments not yet approved for use in humans.


In both clinical and research applications, however, the traits that allow for the generation of “high quality” iPS cells capable of correctly differentiating into the desired tissue with no genetic abnormalities is unclear. “We know there is a link between the topology of the genome and gene expression,” Phillips-Cremins said, “so this motivated us to explore how the genetic material is reconfigured in three dimensions inside the nucleus during the reprogramming of mature brain cells to pluripotency. We found evidence for sophisticated configurations that differ in important ways between iPS cells and embryonic stem cells.”

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Scientists find link between genome and microbiome in Crohn’s disease patients

Scientists find link between genome and microbiome in Crohn’s disease patients | Amazing Science |
Genes linked to Crohn’s disease, an inflammatory bowel disease, might make people’s immune cells miss out on helpful messages sent by friendly gut bacteria.


Good gut bacteria might not help people with Crohn’s disease.

Protective microbial messages go unread in mice and in human immune cells with certain defective genes, researchers report online May 5 in Science. The findings are the first to tie together the roles of genes and beneficial microbes in the inflammatory bowel disease, says biologist Brett Finlay of the University of British Columbia in Vancouver, who was not involved in the new work.


“This is a major step forward in this area,” he says. Human genes and friendly microbes work together to control inflammation, he says. “And when you muck that up, things can go awry.”


In Crohn’s disease, the immune system riles up too easily, trigging chronic inflammation. Scientists don’t know why exactly people’s immune systems go haywire. But researchers have linked the disease to glitches in nearly 200 genes, including ATG16L1 and NOD2, which typically help kill bad bacteria in the gut.


Researchers have also reported that people with Crohn’s have a different collection of gut microbes compared with that of healthy people, says study coauthor and Caltech microbiologist Sarkis Mazmanian.But though “there’s a huge body of literature on the genome and on the microbiome,” he says, “no one knew what the interplay was between the two.”


So his team explored a potential link using a friendly gut microbe called Bacteroides fragilis. The bacteria send out calming messages that tell the immune system to tone down inflammation. Like letters inside envelopes, these messages travel in protective pouches called outer membrane vesicles, or OMVs.


Feeding OMVs to mice typically protects them from developing inflamed colons, or colitis — but not mice lacking the Crohn’s-linked genes ATG16L1 and NOD2. When researchers treated those mice with a colitis-causing chemical, they succumbed to the disease, even after eating OMVs.


Mice with defective versions of ATG16L1 and NOD2 “can’t reap the benefits of the beneficial microbiota,” Mazmanian says.Immune cells from human patients with the defective genes didn’t respond to OMVs either.


The findings suggest that the genes that kill bad bacteria also work with good bacteria to keep people’s immune systems from going out of control, says gastroenterologist Balfour Sartor of the University of North Carolina School of Medicine in Chapel Hill. The work “opens up a new mechanism for protection,” he says.

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Intestinal worms boost immune system in a surprising way

Intestinal worms boost immune system in a surprising way | Amazing Science |

In order to fight invading pathogens, the immune system uses “outposts” throughout the body, called lymph nodes. These are small, centimeter-long organs that filter fluids, get rid of waste materials, and trap pathogens, e.g. bacteria or viruses. Lymph nodes are packed with immune cells, and are known to grow in size, or ‘swell’, when they detect invading pathogens. But now, EPFL scientists have unexpectedly discovered that lymph nodes also produce more immune cells when the host is infected with a more complex invader: an intestinal worm.


The discovery is published in Cell Reports, and has significant implications for our understanding of how the immune system responds to infections. The discovery was made by the lab of Nicola Harris at EPFL. Her postdoc and first author Lalit Kumar Dubey noticed that the lymph nodes of mice that had been infected with the intestinal worm Heligmosomoides polygyrus bakeri had massively grown in size. This worm is an excellent tool for studying how the worm interacts with its host, and is therefore used as a standard throughout labs working in the field.

Lymph nodes have microscopic compartments called “follicles”, where they store a specific type of immune cells, the B-cells. Stored in the follicles, B-cells pump out antibodies into the bloodstream to attack invading pathogens.


The researchers found that the mouse lymph nodes were actually producing more follicles, suggesting they were producing more B-cells in response to the worm infection. Of course, this is not a simple event. Like many biological processes, it involves an entire sequence of molecular signals that result in the formation of new cells and tissue.


The EPFL scientists were able to reconstruct the molecular sequence, which is fairly complex: when the mouse is infected with the intestinal worm, a “cytokine” molecule is produced. This cytokine then stimulates B-cells in the lymph nodes to produce a molecule called a lymphotoxin. The lymphotoxin then interacts with the cells that form the foundation of the actual lymph node – the so-called “stromal cells”. The stromal cells then produce another cytokine, which stimulates the production of new follicles in the lymph node.

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Immune cells glue broken blood vessels back together

Immune cells glue broken blood vessels back together | Amazing Science |

"As we age, tiny blood vessels in the brain stiffen and sometimes rupture, causing "microbleeds." This damage has been associated with neurodegenerative diseases and cognitive decline, but whether the brain can naturally repair itself beyond growing new blood-vessel tissue has been unknown.  


A zebrafish study published on May 3 in Immunity describes for the first time how white blood cells called macrophages can grab the broken ends of a blood vessel and stick them back together. "

Via Mariaschnee
ANDREAS SOFRONIOU's curator insight, May 5, 1:02 AM
Watch immune cells 'glue' broken blood vessels back together
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Facebook, Napster billionaire Parker to fund first-ever CRISPR-CAS9 trial

Facebook, Napster billionaire Parker to fund first-ever CRISPR-CAS9 trial | Amazing Science |
In all the talk of “disruption” and “hacking cancer,” you’d be forgiven for not taking internet billionaire Sean Parker seriously in the life sciences world. But he just got federal backing to run the world’s first-ever CRISPR/Cas9 trial, which could alter the way many diseases, especially cancer, are treated.


You’d be hard-pressed to find another first-in-human trial gain so much attention because, yes, despite all the column inches it’s generated, CRISPR has not yet entered the clinic. But its preclinical activity has caused much hype given its gene-editing capabilities, with its core tech centering on a simple method for reengineering DNA--which may well have profound consequences in treating a number of diseases. 


Recently, a National Institutes of Health (NIH) panel ruled unanimously (but with one abstention) to let the first trial for a CRISPR candidate run. This is just the first step, however, as the FDA as well as the medical centers where it’ll be run will still need to clear the study before it can actually start recruiting and testing patients. So who’s the first pioneer? CRISPR Therapeutics, Caribou Biosciences, Editas ($EDIT), or maybe Intellia ($NTLA)? Surely Novartis ($NVS) must be involved?


Nope, it’s Sean Parker, founder of Napster and the first president of Facebook, who, not short of a few bucks (net worth estimated at $2.4 billion), has stolen a march on the CRISPR pioneers. (Editas was in fact down 7% at the end of play yesterday after the news, with Intellia down 4.5%.) 


The trial, should it gain the regulatory nod, will be run by a group of University of Pennsylvania researchers and funded by the Parker Institute. The study would also be conducted at MD Anderson Cancer Center in Texas and the University of California, San Francisco. Penn will be its spiritual home, however, as Penn’s Dr. Carl June is one of the major innovators in T cell biology. 


Speaking at the Forbes Philanthropy Summit earlier this month, June said the idea is to make T cells, a type of white blood cell, “better than nature made them.” The cells will be edited to lack several genes, including one that allows them to respond to a protein called PD-1, which acts as an off switch that some cancers hijack to evade the immune system.


PD-1 was the last next big thing in cancer, with Merck ($MRK) gaining the first approval for its PD-1 drug Keytruda in 2014, although the market leader, despite being approved second, is Bristol-Myers Squibb’s ($BMY) Opdivo. Roche ($RHHBY) also joined the party earlier this year with its PD-L1 drug Tecentriq.

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Thalidomide Malformations, Anti-cancer Effects Mechanism Finally Found

Thalidomide Malformations, Anti-cancer Effects Mechanism Finally Found | Amazing Science |

Thalidomide was marketed as a sedative in West Germany and some other countries under the brand name “Contergan”. 55 years ago, in 1961, it hit the headlines after having caused horrific deformations in unborn children. Between 5,000 and 10,000 children were affected worldwide. Up to now, the reasons for these disastrous birth defects have remained unclear. Researchers at the Technical University of Munich have at last identified the molecular mechanism of thalidomide.


To this day, more than 2,000 victims across the world still live with the consequences of this tragedy. Soon after the discovery of these devastating side effects, the drug was withdrawn from the market. More recently, however, thalidomide is experiencing a kind of renaissance, as it was coincidentally discovered to inhibit the growth of certain tumors. That is why these latest findings are highly relevant to current cancer therapies, as related substances are essential components of modern cancer treatment regimens.


Two follow-up substances, lenalidomide and pomalidomide, have been approved for cancer treatment. Both thalidomide-derivatives are successfully used to treat certain bone-marrow cancers such as multiple myeloma. While showing stronger anti-tumor potential, they have fewer side effects than thalidomide. Despite this, they still pose a risk of causing severe birth defects and must not be taken during pregnancy.


Thalidomide, lenalidomide and pomalidomide are also known as immunomodulatory drugs (IMiDs). The name is derived from their ability to modify the body’s immune response. Cereblon, a cellular protein, plays an important role in the function of IMiDs. Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Researchers now identified a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147–MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. The researchers found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147–MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, the scientists were able to show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.

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New material kills E. coli bacteria in 30 seconds

New material kills E. coli bacteria in 30 seconds | Amazing Science |

A new material that can kill E. coli bacteria within 30 seconds has been developed by researchers at the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR in Singapore.


Triclosan, a common antibacterial ingredient found in many products such as toothpastes, soaps, and detergents to reduce or prevent bacterial infections, has been linked to making bacteria resistant to antibiotics, with adverse health effects. The European Union has restricted the use of triclosan in cosmetics, and the U.S. FDA is conducting an ongoing review of this ingredient.


To find a more suitable alternative, IBN Group Leader Yugen Zhang, PhD, and his team synthesized a chemical compound made up of molecules linked together in a chain (“imidazolium oligomers”), which they found can kill 99.7% of the E. coli bacteria within 30 seconds. The chain-like structure helps to penetrate the cell membrane and destroy the bacteria.

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First gene mutation explaining development of multiple sclerosis found

First gene mutation explaining development of multiple sclerosis found | Amazing Science |

MS is a neurodegenerative disease in which the immune system attacks the myelin that protects nerve fibers, upsetting the flow of information between the brain and the body. It affects about 2 million people worldwide, and in its more severe, progressive form, no good treatments are available.


About 10% to 15% of MS cases appear to have a hereditary component, but until now researchers conducting genetic studies have found only weak associations between the risk of developing MS and particular gene variants. In contrast, people who carry the newly discovered mutation have a 70% chance of developing the disease, the team determined.


In the current study, the investigators reviewed materials from the Canadian Collaborative Project on Genetic Susceptibility to MS, a large database that contains genetic material from almost 2,000 families across Canada. They looked at a family that had multiple cases of the disease--five cases over two generations--and did exome sequencing to look for rare coding mutations that were present in all family members who had the disease.


After identifying a gene of interest, they went back to the database and found the same mutation in another family with multiple cases of MS. Interestingly, all patients in these families with the mutation presented with the progressive form of MS. "The mutation we found, in a gene called NR1H3, is a missense mutation that causes loss of function of its gene product, LXRA protein," says neuroscientist Weihong Song, Canada Research Chair in Alzheimer's Disease at UBC and the study's other senior author. Together with other members of the same family, LXRA controls transcriptional regulation of genes involved in lipid homeostasis, inflammation, and innate immunity.


Mice with this gene knocked out are known to have neurological problems, including a decrease in myelin production. "There is clear evidence to support that this mutation has consequences in terms of biological function, and the defective LXRA protein leads to familial MS development," Song says.


"One thing that's important to note is that although this mutation is present in only about 1 in 1,000 people with MS, by doing association analysis we've also found common variants in the same gene that are risk factors for progressive MS," Vilariño-Güell adds. "So even if patients don't have the rare mutation, treatments that target this pathway would likely be able to help them."

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Cancer-patient big data can save lives if shared globally

Cancer-patient big data can save lives if shared globally | Amazing Science |

Sharing genetic information from millions of cancer patients around the world could revolutionize cancer prevention and care, according to a paper in Nature Medicine by the Cancer Task Team of the Global Alliance for Genomics and Health (GA4GH). Hospitals, laboratories and research facilities around the world hold huge amounts of this data from cancer patients, but it’s currently held in isolated “silos” that don’t talk to each other, according to GA4GH, a partnership between scientists, clinicians, patients, and the IT and Life Sciences industry, involving more than 400 organizations in over 40 countries. GA4GH intends to provide a common framework for the responsible, voluntary and secure sharing of patients’ clinical and genomic data.


“Imagine if we could create a searchable cancer database that allowed doctors to match patients from different parts of the world with suitable clinical trials,” said GA4GH co-chair professor Mark Lawler, a leading cancer expert fromQueen’s University Belfast. “This genetic matchmaking approach would allow us to develop personalized treatments for each individual’s cancer, precisely targeting rogue cells and improving outcomes for patients.


“This data sharing presents logistical, technical, and ethical challenges. Our paper highlights these challenges and proposes potential solutions to allow the sharing of data in a timely, responsible and effective manner. We hope this blueprint will be adopted by researchers around the world and enable a unified global approach to unlocking the value of data for enhanced patient care.”


GA4GH acknowledges that there are security issues, and has created a Security Working Group and a policy paper that documents the standards and implementation practices for protecting the privacy and security of shared genomic and clinical data.


Examples of current initiatives for clinico-genomic data-sharing include the U.S.-based Precision Medicine Initiative and the UK’s 100,000 Genomes Project, both of which have cancer as a major focus.


Herve Moal's curator insight, May 26, 4:47 AM

l'enjeu du partage des données

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Five genes identified that give your nose its shape

Five genes identified that give your nose its shape | Amazing Science |

Whether you have a huge honker, a puny proboscis, or a snubbed schnoz, the shape of your nose is in your genes. Now, researchers have sniffed out five of those stretches of DNA that control nose and chin shape. The team sequenced the genomes of more than 6000 men and women in Central and South America and used photographs of the participants to categorize 14 of their facial features—from cheekbone protrusion to lip shape. Then, the scientists analyzed whether any of the features were associated with certain genes. GLI3 and PAX1, both known to be involved in cartilage growth, were linked to the breadth of a person’s nostrils;DCHS2, also related to cartilage, controlled nose pointiness; RUNX2, which drives bone development, was associated with the width of the nose bridge, the upper area of the nose; and EDAR, which has previously been linked to ear and tooth shape and hair texture, affected chin protrusion. The results, published online today in Nature Communications, may help shed light on how the human face evolved and why different ethnicities have distinct facial features. Moreover, the research could help forensic scientists reconstruct faces based on genetic samples.

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Duke's Poliovirus Oncolytic Therapy Wins "Breakthrough" Status

Duke's Poliovirus Oncolytic Therapy Wins "Breakthrough" Status | Amazing Science |

The recombinant poliovirus therapy developed at the Preston Robert Tisch Brain Tumor Center at Duke Health has been granted “breakthrough therapy designation” from the U.S. Food and Drug Administration.


Duke’s poliovirus therapy is an immunotherapy developed in the laboratory of Matthias Gromeier, M.D., a professor in the departments of Neurosurgery, Molecular Genetics and Microbiology, and Medicine at Duke University School of Medicine. 


Using a modified form of poliovirus that has been altered to eliminate harm, the therapy preferentially attacks cancer cells, which have an abundance of receptors that work like magnets to attract the poliovirus. The modified poliovirus then kills the infected tumor cells while also igniting an additional immune response.


A phase I clinical trial using the therapy was launched in 2012 to determine an optimal dose of the novel treatment among adult patients with glioblastoma whose cancer had returned after receiving traditional therapy.


Early testing found that lower doses of the treatment were superior to higher doses. Of 23 glioblastoma patients enrolled at the optimal dose level, 15 are still alive and enrollment is ongoing. Three patients treated early using different dosages are still alive more than 36 months after treatment. With current standard therapy, the median survival time for people with glioblastoma is 14.6 months. 


The Duke team is moving to expand its work and open a clinical trial for children with brain tumors, which is expected to begin enrollment before year’s end. The researchers have also received federal grants to explore the therapy’s effect on solid tumors. Laboratory studies are already underway in breast cancer models.

Via Krishan Maggon
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Genetically Modified Crops Are Safe, National Academies Report Finds

Genetically Modified Crops Are Safe, National Academies Report Finds | Amazing Science |

Genetically modified crops on the market are not only safe, but appear to be good for people and the environment, experts determined in a report released Tuesday.


But the National Academies of Sciences, Engineering, and Medicine are not just asking people to take their word for it. They're putting the evidence up on a website so skeptics — and they know there are plenty of them — can check for themselves.


"The committee delved into the relevant literature, heard from 80 diverse speakers, and read more than 700 comments from members of the public to broaden its understanding of issues surrounding GE crops," the report reads. Panel members read more than 900 reports.


"It was tiring but worthwhile, because it really brought to our attention a lot of studies we would not have looked at," said Dominique Brossard, chair of the department of Life Sciences Communication at the University of Wisconsin.


"Our process was really, really inclusive and attempted to address as much as possible the concerns that were raised by public comments."


A lot of concern centered on health effects. "The committee received a number of comments from people concerned that GE food consumption may lead to higher incidence of specific health problems including cancer, obesity, gastrointestinal tract illnesses, kidney disease, and such disorders as autism spectrum and allergies," the report reads. "The committee also examined epidemiological data on incidence of cancers and other human-health problems over time and found no substantiated evidence that foods from GE crops were less safe than foods from non-GE crops."


Their conclusions:

  • There is no evidence of large-scale health effects on people from genetically modified foods
  • There is some evidence that crops genetically engineered to resist bugs have benefited people by reducing cases of insecticide poisoning
  • Genetically engineered crops to benefit human health, such as those altered to produce more vitamin A, can reduce blindness and deaths die to vitamin A deficiency
  • Using insect-resistant or herbicide-resistant crops did not damage plant or insect diversity and in some cases increased the diversity of insects.
  • Sometimes the added genes do leak out to nearby plants - a process called gene flow - but there is no evidence it has caused harm.
  • In general, farmers who use GM soybean, cotton, and corn make more money but it does depend on how bad pests are and farming practices.
  • GM crops do reduce losses to pests
  • If farmers use insect-resistant crops but don't take enough care, sometimes pest insects develop resistance

Outside experts said the report was very thorough and scientifically sound. It clearly shows that the anti-GMO hype is non-justified.


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Aggregated SOD1 protein in nerve cells can cause ALS

Aggregated SOD1 protein in nerve cells can cause ALS | Amazing Science |

Persons with the serious disorder ALS, can have a genetic mutation that causes the protein SOD1 to aggregate in motor neurons in the brain and spinal cord. Researchers at Umeå University have discovered that, when injected into mice, the SOD1 aggregation spreads rapidly leading to ALS. The discovery has been described in theJournal of Clinical Investigation.


ALS, Amyotrophic lateral sclerosis, is a disorder which causes death of motor neurons in the brain and the spinal cord in charge of controlling muscles. This leads to progressive paralysis and death, often due to carbon dioxide narcosis.

“The occurrence of SOD1 aggregates in nerve cells in ALS patients has been known for a while,” says Thomas Brännström, professor of Pathology at Umeå University and one of the authors of the article.


“But it has long been unclear what role the SOD1 aggregates play in the disease progression in humans carrying hereditary traits for ALS. We have now been able to show that the SOD1 aggregates start a domino effect that rapidly spreads the disease up through the spinal cord of mice. We suspect that this could be the case for humans as well.”


Researchers at the Departments of Medical Biosciences and Pharmacology and Clinical Neuroscience at Umeå University have examined whether the accumulation of the SOD1 aggregates inside nerve cells drives the ALS disease or if it is a harmless side-effect. The research team has been able to identify two different kinds of SOD1 aggregates in mice. The results showed that both kinds caused a spread of SOD1 aggregation when a small amount was injected into the spinal cord of mice. The accumulation of aggregates progressed in nerve cells along the entire spinal cord of the mice at the same time as it led to a rapid and eventually mortal outcome of the disease.


“The results show that the aggregation of SOD1 plays a critical role in the disease progression – a research hypothesis that ALS researchers in Umeå long has based its work upon,” says Stefan Marklund, professor of Clinical Chemistry. “More research is necessary, but our aim is to develop interventions that prevent or stop the fatal course of the disease in carriers of hereditary traits of ALS.”

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Zika anniversary: What has been learned?

Zika anniversary: What has been learned? | Amazing Science |

One year ago, Brazil reported the first laboratory-confirmed cases of Zika. The virus had cropped up elsewhere in a few earlier outbreaks, too, but it didn’t seem all that threatening at the time. Zika symptoms were generally pretty mild — or even nonexistent, the Pan American Health Organization and the World Health Organization reported in an epidemiological alert May 7, 2015. The alert made no mention of pregnant women, babies or microcephaly. In fact, it noted: “Complications (neurological, autoimmune) are rare.”


What a difference a year makes. Now scientists have convincingly tied Zika infection to birth defects, and suspect it’s behind an uptick in neurological disorders in adults, too. But researchers are still figuring out how the virus acts, and how to stop it. A vaccine is in the works, but could take years.


So Zika-fighting tactics have gotten creative. A new billboard in Brazil lures mosquitoes in with spritzes of humanlike scent, and then traps them inside a chamber to die. (It kills hundreds of mosquitoes a day, the billboard’s makers tout, but scientists have yet to weigh in.) Researchers have recently explored other methods to rein in Zika.


This and more from recent research:

  • The best weapon against Zika may be a mosquito-infecting bacteria. Mosquitoes harboringWolbachia pipientis resisted infection from two strains of Zika virus circulating in Brazil, researchers report May 4 in Cell Host & Microbe. And if Wolbachia-carrying mosquitoes do get infected, they’re less likely to transmit the virus. Releasing these mosquitoes in the wild could help halt Zika’s spread
  • An antimalarial drug called chloroquine could also work against Zika. When added to human brain cells and mouse minibrains in the lab, the drug helped prevent Zika infection. It also kept minibrains looking somewhat healthy, researchers report May 2 at Chloroquine is a promising candidate for clinical trials, the authors write, because it’s safe for use in pregnant women.
  • Zika kills brain cells by cranking up production of a protein that triggers cellular self-destruction, researchers report May 6 in Cell Stem Cell. Scientists knew that infection with the virus could kill cells, shrinking minibrains grown in the lab, but until now, they didn’t understand how. The protein, an immune molecule called TLR3, could act as a target for therapies.
  • A new paper-based Zika test could offer doctors a quick and easy way to detect the virus. The test senses Zika RNA and can differentiate between African and American strains, scientists report May 6 in Cell. Though still in the proof-of-concept stage, the test was able to confirm Zika’s presence in samples from an infected macaque. The news comes on the heels of the FDA’s recent approval of a commercial test for Zika.
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Second skin: Transparent polymer film smoothes sagging skin back into shape

Second skin: Transparent polymer film smoothes sagging skin back into shape | Amazing Science |

Materials scientists working with cosmetics firms have developed a transparent film that, for the first time, mimics the skin’s youthful elasticity. The silicone-based coating can be smeared onto the face or other areas of the body through two gel applications. Once hardened, it clings closely to the skin for more than 16 hours, says Robert Langer, a bioengineer at the Massachusetts Institute of Technology in Cambridge, who co-led development of the material.


The film — which Langer’s team dubs ‘second skin’ — can reduce the appearance of bags under the eyes and wrinkles, and can increase the elastic recoil of skin when it is pinched, he and colleagues report in a paper published in Nature Materials1.


It also acts as a barrier that prevents water loss from dry skin, they report, suggesting that besides its cosmetic use, the film might offer an alternative to greasy ointments for people with skin complaints such as eczema, although it hasn't yet been trialled for that idea.


A version of the film has been on sale as a daily treatment through dermatologists since 2014, marketed by a firm called Living Proof in Cambridge, Massachusetts, that Langer co-founded — and which film star Jennifer Aniston has invested in. Beauty bloggers writing about the product two years ago said that it was like ‘shapewear for skin’.


Langer calls that product a "very early version" of the material described in the research paper, which marks the first time that the film has been detailed in the scientific literature. “Up until now, there has been nothing that could restore the elastic property of skin, and this material does that,” says Barbara Gilchrest, a dermatologist at Harvard Medical School in Boston, Massachusetts, and a co-author of the report. John Rogers, a biomaterials scientist at the University of Illinois at Urbana–Champaign, says that the team’s results are “impressive”.


The team screened more than 100 variant polymers to create the elastic yet transparent film. Users first smear on a gel-like polymer that is based on siloxanes (chains of molecules containing silicon and oxygen), and then add another gel that contains a platinum-based catalyst. This cross-links the polymer chains together to toughen up the material — effectively ‘setting’ the film — which is only 40–70 micrometres thin; Langer says it is "essentially invisible".

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Scientists hail 'milestone' genomic breast cancer study

Scientists hail 'milestone' genomic breast cancer study | Amazing Science |
Scientists say they now have a near-perfect picture of the genetic events that cause breast cancer, which they hope will unlock new ways of treating the disease.


The study, published in Nature, has been described as a "milestone" moment that could help unlock new ways of treating and preventing the disease. The largest study of its kind unpicked practically all the errors that cause healthy breast tissue to go rogue.


Cancer Research UK said the findings were an important stepping-stone to new drugs for treating cancer. To understand the causes of the disease, scientists have to understand what goes wrong in our DNA that makes healthy tissue turn cancerous. The international team looked at all 3 billion letters of people's genetic code - their entire blueprint of life - in 560 breast cancers. They uncovered 93 sets of instructions, or genes, that if mutated, can cause tumours. Some have been discovered before, but scientists expect this to be the definitive list, barring a few rare mutations.


Prof Sir Mike Stratton, the director of the Sanger Institute in Cambridge which led the study, said it was a "milestone" in cancer research. "There are about 20,000 genes in the human genome. It turns out, now we have this complete view of breast cancer - there are 93 of those genes that if mutated will convert a normal breast cell into a breast cancer cell. That is an important piece of information," he stated. "We hand that list over to the universities, the pharmaceuticals, the biotech companies to start developing new drugs because those mutated genes and their proteins are targets for new therapeutics. There are now many drugs that have been developed over the last 15 years against such targets which we know work."

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