#New gene therapy success in a rare disease of the immune system Wiskott-Aldrich syndrome is a rare congenital immune and platelet deficiency
which is linked X and has estimated an prevalence of 1/250,000. It is caused by mutations in the gene encoding the was expressed protein (WASP in hematopoietic cells.
This disease, which primarily affects boys, causes bleeding, severe and recurrent infections, severe eczema and in some patients autoimmune reactions and the development of cancer.
The only treatment available today is bone marrow transplantation, which requires a compatible donor and can itself cause serious complications.
The Phase I/II study with Genethon as the promoter, was launched in December 2010 and conducted in Paris
and London to treat severely ill patients without a compatible donor. This study, which is ongoing,
assesses the feasibility and efficacy of gene therapy in this indication. The article published in JAMA reports the results for the first six patients, aged 8 months to 16 years,
where the monitoring period allowed assessment of the initial effects of the treatment. The treatment involves collected blood stem cells carrying the genetic anomaly of patients
and corrected them in the laboratory by introducing a healthy WAS gene using a lentiviral vector developed
and produced by Genethon. The corrected cells were reinjected into patients who in parallel were treated with chemotherapy to suppress their defective stem cells
and autoimmune cells to make room for new corrected cells. After reinjection, these cells were differentiated then into the various cell lines that make up the blood (red and white cells, platelets.
To date treated patients showed significant clinical improvement. Severe eczema and severe infection disappeared in all cases.
Arthritis was eliminated in one patient and another saw major improvement in vasculitis of the lower limbs and was able to return to normal physical activity without a wheelchair.
However, the rate of corrected platelets varies from one patient to another. Fulvio Mavilio, Chief Scientific Officer Genethon:"
"We are all very happy and encouraged by the results of this study. It is the first time that a gene therapy based on genetically modified stem cells is tested in a multicenter, international clinical trial that shows a reproducible and robust therapeutic effect in different centers and different countries.
For very rare diseases such as WAS, multicenter clinical trials are the only effective way of proving the safety
and efficacy of gene therapy and having it rapidly approuved and made available to all patients.
We are following the same approach for other rare and less rare blood diseases.""Frdric Revah, CEO of Genethon, the laboratory of the AFM-Telethon and the trial sponsor, said"These first results of our clinical trial for the treatment of Wiskott Aldrich syndrome are very encouraging.
They illustrate not only the ability of Genethon to carry out the upstream research to develop treatments for these rare and complex diseases,
but also to construct and conduct international clinical trials, to produce these advanced therapy products, to work with international teams and to manage the regulatory aspects of the trials in France and abroad.
These are skills that we implement for other international trials of gene therapy for rare genetic diseases of the immune system
blood, muscle, vision or liver...We will continue the current study with the objective of providing treatment for patients."
"Marina Cavazzana:""The results obtained in this multicenter clinical trial constitute an important therapeutic advance (overhang)
because they concern a complex pathology which affects almost all of blood cells with dramatic clinical consequences.
After transfer of gene, the patients showed a significant clinical improvement due to the reexpression of the protein WASP in the cells of the immune system.
The efficiency of the treatment of such a deficit for which a high level of correction of hematopoietic stem cells is required,
indicates that it is from now on justifiable to hope to treat other complex genetic diseases as those affecting red blood cells."
"Professor Thrasher says:""This is a very powerful example of how gene therapy can offer highly effective treatment for patients with complex and serious genetic disease.
It also excitingly demonstrates the potential for treatment of a large number of other diseases for
which existing therapies are either unsatisfactory or unavailable
#Printing silicon on paper, with lasers Recently, a group of researchers at Delft University of Technology,
in The netherlands, has pioneered a method that allows silicon itself, in the polycrystalline form used in circuitry,
to be produced directly on a substrate from liquid silicon ink with a single laser pulse--potentially ousting its pale usurpers.
The capacity for printing silicon ink onto substrates has existed for some time, but necessitated a 350 C thermal annealing step--far too hot for many of the flexible surfaces that made production appealing in the first place.
The researcher's new method completely bypasses this step transforming the liquid silicon directly into polysilicon.
They discuss their research this week in Applied Physics Letters, from AIP Publishing.""It was said very simple
Ryoichi Ishihara, the professor who led the research team at Delft University of Technology, with collaborators at the Japan Advanced Institute of Science and Technology in Ishikawa, Japan."
"We coated liquid polysilane directly on paper by doctor-blading, or skimming it by a blade directly in an oxygen-free environment.
Then we annealed the layer with an excimer laser a conventional tool used for manufacturing smartphone displays.
And it worked, "Ishihara said. The laser blast only lasted a few tens of nanoseconds, leaving the paper completely intact.
In testing its conductive performance, Ishihara and his colleagues found that thin-film transistors using the laser-printed layer exhibited mobilities as high as those of conventional poly-silicon conductors.
The most immediate application of this printing capacity is in wearable electronics as it allows for the production of fast, low-power and flexible transistors at a remarkably low cost.
Ishihara believes the future of the project, which involves improving the production process of the thin-film transistors to include additional non-silicon layers,
will hold a wealth of possible further applications.""The process can be expanded to biomedical sensor and solar-cell areas,
"Ishihara said, "and will also realize stretchable--and even edible--electronics
#Frequent genomic alteration is identified in a rare subset of breast cancer Genomic profiling identifies genomic mutations in a gene associated with a rare subset of breast cancer,
research shows--mutations that cannot otherwise be identified with standard clinical analysis of cells and tissue.
The findings could have therapeutic implications specific to this rare form of the disease, say the authors.
Research from Rutgers Cancer Institute of New jersey shows genomic profiling identifies genomic mutations in a gene associated with a rare subset of breast cancer--mutations that cannot otherwise be identified with standard clinical analysis of cells and tissue.
The findings being presented as part of a poster presentation at the Annual Meeting of the American Association for Cancer Research (AACR) being held in Philadelphia,
could have therapeutic implications specific to this rare form of the disease, say the authors.
Invasive lobular carcinoma is a cancer that starts in the lobules, an area of the breast where milk is produced.
It is normally very sensitive to estrogen-targeting therapies because of high expression of the estrogen receptor protein,
but rarely shows high expression of the HER2 protein. Pleomorphic invasive lobular carcinoma is a unique subset of lobular breast cancer that has abnormally aggressive tumor cells and results in poorer outcomes than the classic lobular breast cancer.
Recently alterations were found in the ERBB2 gene in lobular breast cancers that recur after initial treatment.
The ERBB2 gene directs the cancer cell to make the HER2 protein which is tested routinely for using standard pathologic techniques.
As part of the precision medicine initiative at the Cancer Institute of New jersey, investigators--which include colleagues from Rutgers Robert Wood Johnson Medical school and RUCDR Infinite Biologics, the world's largest university-based biorepository,
located within the Human genetics Institute of New jersey--wanted to define the relationship of ERBB2 alterations in the pleomorphic form of the disease."
"Figuring out specific differences that are not visible under the microscope allows us to intervene with more appropriate and potentially lifesaving therapy.
With genomic sequencing detecting ERBB2 alterations in this form of cancer, we have an opportunity to identify anticancer therapies that would specifically target that abnormality
and that would otherwise not be given to those patients who could benefit. These genomic abnormalities would be overlooked with current,
standard of care laboratory testing for breast cancer,"says lead author Kim M. Hirshfield, MD, Phd, breast medical oncologist at the Cancer Institute and assistant professor of medicine at Rutgers
Robert Wood Johnson Medical school. Utilizing the invasive breast cancer data set of 962 cases in The Cancer Genome Atlas
all breast cancers with alterations in the CDH1 gene (that gives instructions to make a protein that causes cancer cells to stick to one another
and defines lobular breast cancers) were identified. Tumors were evaluated by a pathologist at the microscopic level to classify them as either classic or pleomorphic lobular breast cancer.
Independent identification of ERBB2 gene alterations was completed and frequency of that alteration, as well as others in the PTEN, PIK3CA and TP53 genes, were determined.
An additional 16 cases from the Cancer Institute were evaluated using an advanced form of tumor DNA sequencing at RUCDR.
Of 116 eligible breast cancers from The Cancer Genome Atlas 86 were invasive lobular breast cancer. Of that number, 21 cases were found to be the pleomorphic type.
Nine ERBB2 mutations (42.9 percent) and three amplifications (14.3 percent) were found in the pleomorphic type
and none were found in the classic type. There were no significant differences in the frequency of the other gene alterations examined between the two types of cancer.
With that, investigators say the alterations in the ERBB2 gene strongly associate with pleomorphic lobular breast cancer but not the classic form of the disease.
Data from the additional 16 cases from the Cancer Institute validate the findings observed on breast cancers from The Cancer Genome Atlas."
"In identifying a specific abnormality in a patient's cancer instead of the overall organ where it first presented,
the opportunity exists to provide tailored therapies for patients,"notes Lorna Rodriguez, MD, Phd, director of the precision medicine initiative at the Cancer Institute and professor of obstetrics, gynecology and reproductive sciences
at Robert Wood Johnson Medical school.""Advances in genomic sequencing are helping clinicians go beyond a'one size fits all'approach for treatment.""
""Along with helping to guide the use of existing treatments, such findings can also aid in developing the next generation of therapies through clinical trials.
It is our aim at Rutgers Cancer Institute of New jersey to build upon this work,"notes senior author of the work, Shridar Ganesan, MD, Phd, associate director for translational science at the Cancer Institute
and associate professor of medicine and pharmacology at Robert Wood Johnson Medical school l
#Natural reparative capacity of teeth elucidated These results are published in the journal Stem Cells. The tooth is a mineralised organ, implanted in the mouth by a root.
The"living"part of the tooth or dental cavity is the dental pulp (in yellow in the photograph shown opposite) composed of vessels and nerves.
Around it is a hard substance, the dentine or ivory, which is covered in turn by an even harder tissue, the enamel.
When a dental lesion appears, the dormant stem cells in the pulp awaken and try to repair the tooth by an unknown process.
In this study the researchers from Inserm and Paris Descartes University at Unit 1124,"Toxicology, Pharmacology and Cellular Signaling,"have succeeded in extracting
and isolating tooth stem cells by working on the pulp from the mouse molar. The researchers were
thus able to analyse the cells in detail, and identify 5 specific receptors for dopamine and serotonin on their surface,
two neurotransmitters that are essential to the body (see schema on page 2). The presence of these receptors on the surface of these stem cells indicated that they had the ability to respond to the presence of dopamine and serotonin in the event of a lesion.
The researchers naturally wondered what cells might be the source of these neurotransmitters a warning signal.
It turns out that the blood platelets, activated by the dental lesion, are responsible for releasing a large quantity of serotonin and dopamine.
Once released, these neurotransmitters then recruit the stem cells to repair the tooth by binding to their receptors (see schema on page 2). The research team was able to confirm this result by observing that dental repair was absent in rats with modified platelets that do not produce serotonin or dopamine,
i e. in the absence of the signal.""In stem cell research, it is unusual to be simultaneously able to isolate cell lines,
In this work, we have been able, unexpectedly, to explore the entire mechanism, "explains Odile Kellermann, leader of the team from Inserm and Paris Descartes University,
and the main author of this work. To take things a stage further, the researchers tried to characterise the different receptors they found.
One of the 5 receptors does not seem to affect the repair process. On the other hand, the other 4 turn out to be involved strongly in the repair process.
"Currently, dentists use pulp capping materials (calcium hydroxide) and tricalcium phosphate-based biomaterials to repair the tooth and fill lesions.
Our results lead us to imagine unprecedented therapeutic strategies aimed at mobilising the resident pulpal stem cells
in order to magnify the natural reparative capacity of teeth without use of replacement materials, "concludes Odile Kellermann.
#Researchers discover new drugs to combat the root cause of multiple sclerosis At the pathological level,
MS is a disease in which the immune system attacks the protective myelin sheath, a type of insulation that covers nerves,
"Current therapies focus on stopping immune system attacks, slowing the progression of the disease. Our research is focused on trying to repair the brain itself,
to stop the disease rather than slow it, "said Robert Miller, Ph d.,co-author of the study and senior associate dean for research, Vivian Gill Distinguished Research Professor,
and professor of anatomy and regenerative biology at the George washington University School of medicine and Health Sciences."
"While successful in vivo, we're looking forward to continuing our research through further testing of miconazole and clobetasol,
taking the next steps to finding treatments for MS."Performed at Case Western Reserve University, researchers discovered the therapeutic compounds for enhancing myelination from oligodendrocyte progenitor cells through screening a library of bioactive small molecules.
Oligodendrocyte progenitor cells are stem cells found in the central nervous system and the principal source of myelinating oligodendrocytes.
Finding this cellular target for pharmacological intervention, Miller and co-author Paul Tesar, Ph d.,the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics
and associate professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of medicine, found seven drugs that enhance generation of mature oligodendrocytes
and found that miconazole and clobetasol could promote myelination. Miconazole was found to function directly as a remyelinating drug with no effect on the immune system,
much of the stem cell field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine,
"said Tesar, also a New york Stem Cell Foundation Robertson Investigator and member of the National Center for Regenerative medicine."
#Researchers develop Ebola treatment effective 3 days after infection The study results, in the April 22 edition of Nature Journal, demonstrated that the treatment is the first to be shown effective against the new Makona outbreak strain of Ebola in animals that were infected with the virus
and exhibited symptoms of the disease. The treatment uses a sequence specific short strand of RNA, known as sirna,
"said UTMB's Thomas Geisbert, professor of microbiology and immunology.""We were able to protect all of our nonhuman primates against a lethal Makona Ebola infection
when treatment began three days following infection. At this point, those infected showed clinical signs of disease
and had detectable levels of virus in their blood.""Although all infected animals showed evidence of advanced disease,
those receiving treatment had milder symptoms and recovered fully. The untreated controls succumbed to the disease on days eight and nine,
which is reported similar to that in the field after patients begin showing symptoms of Ebola. This treatment also protected against liver
and kidney dysfunction and blood disorders that occur during an Ebola infection. These results indicate that the treatment may confer protective benefits that go beyond improving survival rates and effective control of virus levels in the body."
"This study demonstrates that we can rapidly and accurately adapt our sirna-LNP technology to target genetic sequences emerging from new Ebola virus outbreaks,
"said Dr. Mark Murray, president and CEO of Tekmira Pharmaceuticals. The Tekmira sirna-based therapeutic is now being evaluated in Ebola-infected patients in Sierra leone e
#Discovery could impact study of chronic pain conditions Researchers at the IRCM led by Artur Kania,
Phd, uncovered the critical role in pain processing of a gene associated with a rare disease.
Mutations in this gene also cause a rare human disease called the Nail-patella syndrome (NPS
"By studying mouse models, we first showed this gene is essential for the survival of neurons
Phd student in the same laboratory and co-author of the article.""Our results demonstrate the critical role of Lmx1b for mechanical and thermal pain processing.""
"Our work also provides invaluable knowledge for the study of chronic pain and other pain conditions
#From metal to insulator and back again Metals are compounds that are capable of conducting the flow of electrons that make up an electric current.
Other materials, called insulators, are not capable of conducting an electric current. At low temperatures, all materials can be classified as either insulators or metals.
New work homes in on the physics underlying the recently discovered fact that some metals stop being metallic under pressure.
New work from Carnegie's Russell Hemley and Ivan Naumov hones in on the physics underlying the recently discovered fact that some metals stop being metallic under pressure.
Their work is published in Physical Review Letters. Metals are compounds that are capable of conducting the flow of electrons that make up an electric current.
Other materials, called insulators, are not capable of conducting an electric current. At low temperatures, all materials can be classified as either insulators or metals.
Insulators can be pushed across the divide from insulator to metal by tuning their surrounding conditions,
particularly by placing them under pressure. It was believed long that once such a material was converted into a metal under pressure,
it would stay that way forever as the pressure was increased. This idea goes back to the birth of quantum mechanics in the early decades of the last century.
But it was discovered recently that certain groups of metals become insulating under pressure-a remarkable finding that was thought not previously possible.
For example lithium goes from being a metallic conductor to a somewhat resistant semiconductor under around 790,000 times normal atmospheric pressure (80 gigapascals)
and then becomes fully metallic again under around 1. 2 million times normal atmospheric pressure (120 gigapascals).
Sodium enters an insulating state at pressures of around 1. 8 million times normal atmospheric pressure (180 gigapascals.
Hemley and Naumov wanted to determine the unifying physics framework underlying these unexpected metal-to-insulator-to-metal transitions."
when metals will become insulators under pressure, as well as the reverse, the when-insulators-can-become-metals transition,
"Naumov said. The onsets of these transitions can be determined by the positions of electrons within the basic structure of the material.
Hemley and Naumov demonstrated that for a metal to become an insulator, these reduced-spacing overlaps must be organized in a specific kind of asymmetry that was recognized not previously.
The work will have implications for the search for new energy materials.""Hemley said d
#Metamaterials shine bright as new terahertz source Metamaterials allow design and use of light-matter interactions at a fundamental level.
An efficient terahertz emission from two-dimensional arrays of gold split-ring resonator metamaterials was discovered as a result of excitation by a near-infrared pulsed laser.
Terahertz waves are used in noninvasive imaging and sensing technology, in addition to information, communication, processing, and data storage technologies.
Despite their widely recognized importance, however, there are few terahertz sources presently available due to the limitations of natural materials.
This discovery opens new ways to use metamaterials for these important applications. Broadband terahertz sources offer exciting possibilities to study fundamental physics principles
To solve these challenges consider metamaterials; materials that allow control of the properties of light-matter interactions at the fundamental level.
The building blocks of metamaterials, known as split-ring resonators, can be designed to exhibit strong electric and magnetic response to electromagnetic fields over a wide frequency range, from terahertz to infrared.
when a two-dimensional array of nanometer-sized gold metamaterial resonators is illuminated by a tunable near-infrared femtosecond laser,
with wavelengths matching the magnetic resonance of the metamaterial, a strong broadband of terahertz electromagnetic waves is emitted.
Further, these new metamaterials could allow integration of terahertz optoelectronics with high-speed telecommunications. DOE Office of Science, Basic energy Sciences (experiments.
Theory research was supported by the US Office of Naval Research and the National Science Foundation.
and the Karlsruhe Institute of technology (KIT) through the DFG-Center for Functional Nanostructures (CFN
#Ultra-sensitive sensor detects individual electrons In the same Cambridge laboratory in the United kingdom where The british physicist J. J. Thomson discovered the electron in 1897,
European scientists have developed just a new ultra-sensitive electrical-charge sensor capable of detecting the movement of individual electrons."
"The device is much more compact and accurate than previous versions and can detect the electrical charge of a single electron in less than one microsecond,"M. Fernando Gonzlez Zalba,
and its authors predict that these types of sensors, dubbed'gate sensors, 'will be used in quantum computers of the future to read information stored in the charge or spin of a single electron."
"We have called it a gate sensor because, as well as detecting the movement of individual electrons, the device is able to control its flow
as if it were an electronic gate which opens and closes, "explains Gonzlez Zalba. The researchers have demonstrated the possibility of detecting the charge of an electron with their device in approximately one nanosecond,
the best value obtained to date for this type of system. This has been achieved by coupling a gate sensor to a silicon nanotransistor where the electrons flow individually.
In general, the electrical current which powers our telephones fridges and other electrical equipment is made up of electrons:
minuscule particles carrying an electrical charge travelling in their trillions and whose collective movement makes these appliances work.
However, this is not the case of the latest cutting-edge devices such as ultra-precise biosensors, single electron transistors, molecular circuits and quantum computers.
These represent a new technological sector which bases its electronic functionality on the charge of a single electron,
a field in which the new gate sensor can offer its advantages s
#Researchers add a new wrinkle to cell culture Using a technique that introduces tiny wrinkles into sheets of graphene,
researchers from Brown University have developed new textured surfaces for culturing cells in the lab that better mimic the complex surroundings in
"said Ian Y. Wong, assistant professor of engineering and one of the study's authors.""We've shown that you can make textured environments for cell culture fairly easily using graphene."
"Traditionally, cell culture in the lab has been done in petri dishes and on other flat surfaces. But in the body, cells grow in considerably more complex environments.
Research has shown that a cell's physical surroundings can influence its shape, physiology, and even the expression of its genes.
So the Brown team turned to a darling of the nanotech world: graphene, the carbon nanomaterial.
To make their textured surfaces, the researchers used graphene oxide dispersed in a solution and dabbed onto a substrate made from a rubbery silicon material.
says Mehrdad Kiani, a Brown undergraduate student and member of the research team.""Other methods are much more labor-intensive,
and mouse fibroblast cells (cells involved in wound healing) on flat graphene sheets and on wrinkled ones.
multipolar and not aligned,"said Evelyn Kendall Williams, another undergraduate member of the research team."
or perhaps as biomimetic surfaces for implantable tissue scaffolds or neural implants. The work was the result of collaboration between Wong's biomedical engineering lab and the lab of Robert Hurt, professor of engineering at Brown,
who focuses on carbon nanomaterials.""This is a new application for graphene, "Hurt said.""We are just beginning to realize all of the innovative ways one can use this atomically thin and flexible building block to make new materials and devices."
"The team recently received seed funding from Brown's Office of the Vice president for Research to continue the work.
Kiani and Williams both received undergraduate research funding from Brown to work on the project during the summer of 2014.
Kiani was funded through the Vincent and Ruby Dimase Undergraduate Summer Fellowship offered through the Brown School of engineering.
Williams received a Karen T. Romer Undergraduate Teaching and Research Award. Graduate students Zhongying Wang, Daniel Tonderys, Susan E. Leggett, Ruben Spitz Steinberg,
and Yang Qiu were coauthors on the paper. The initial work was supported by the National Science Foundation (CBET-1132446 and CBET-1344097) and National institutes of health (5t32es007272-23;
Wong received seed funding from Jason and Donna Mcgraw Weiss s
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