PHILADELPHIA HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

"We have 43 patients and they are all healthy," says senior author Carl June, MD, a professor of Pathology and Laboratory Medicine at Penn Medicine. "And out of those, 41 patients show long term persistence of the modified T cells in their bodies."

Early gene therapy studies raised concern that gene transfer to cells via retroviruses might lead to leukemia in a substantial proportion of patients, due to mutations that may arise in genes when new DNA is inserted. The new long-term data, however, allay that concern in T cells, further buoying the hope generated by work June's team published in 2011 showing the eradication of tumors in patients with chronic lymphocytic leukemia using a similar strategy.

"If you have a safe way to modify cells in patients with HIV, you can potentially develop curative approaches," June says. "Patients now have to take medicine for their whole lives to keep their virus under control, but there are a number of gene therapy approaches that might be curative." A lifetime of anti-HIV drug therapy, by contrast, is expensive and can be accompanied by significant side effects.

They also note that the approach the Penn Medicine team studied may allow patients with cancers and other diseases to avoid the complications and mortality risks associated with more conventional treatments, since patients treated with the modified T cells did not require drugs to weaken their own immune systems in order for the modified cells to proliferate in their bodies after infusion, as is customary for cancer patients who receive stem cell transplants.

To demonstrate the long-term safety of genetically modified T cells, June and colleagues have followed HIV-positive patients who enrolled in three trials between 1998 and 2002. Each patient received one or more infusions of their own T cells that had been genetically modified in the laboratory using a retroviral vector. The vector encoded a chimeric antigen receptor that recognizes the HIV envelope protein and directs the modified T cell to kill any HIV-infected cells it encounters.

As is standard for any trial, the researchers carefully monitored patients for any serious adverse events immediately after infusion -- none of which were seen. Additionally, because of the earlier concerns about long-term side effects, the U.S. Food and Drug Administration also asked the team to follow the patients for up to 15 years to ensure that the modified T cells were not causing blood cancers or other late effects. Therefore, each patient underwent an exam and provided blood samples during each of the subsequent years.

Now, with more than 500 years of combined patient safety data, June and colleagues are confident that the retroviral vector system is safe for modifying T cells. By contrast, June notes, the earlier, worrying side effects were seen when viral vectors were used to modify blood stem cells. The new results show that the target cell for gene modification plays an important role in long-term safety for patients treated. "T cells appear to be a safe haven for gene modification," June says.

The multi-year blood samples also show that the gene-modified T cell population persists in the patients' blood for more than a decade. In fact, models suggest that more than half of the T cells or their progeny are still alive 16 years after infusion, which means one treatment might be able to kill off HIV-infected cells for decades. The prolonged safety data means that it might be possible to test T cell-based gene therapy for the treatment of non-life threatening diseases, like arthritis.

"Until now, we've focused on cancer and HIV-infection, but these data provide a rationale for starting to focus on other disease types," June says. "What we have demonstrated in this study and recent studies is that gene transfer to T cells can endow these cells with enhanced and novel functions. We view this as a personalized medicine platform to target disease using a patient's own cells."

Read more here:
Genetically Modified T Cell Therapy Shown to be Safe, Lasting in Decade-Long Penn Medicine Study of HIV Patients

By Elizabeth Lopatto - Wed May 02 18:00:00 GMT 2012

HIV patients given gene therapy more than a decade ago are healthy and the altered DNA they received remains stable in their bodies, according to a study that scientists say proves the treatment may safely be tested as a way to attack other illnesses.

All except two of 43 people treated with genetically- altered versions of their own infection-fighting T cells were healthy as many as 11 years later, according to the research reported today in the journal Science Translational Medicine.

Previous uses of gene therapy in experiments have suggested that leukemia caused by the viruses that transfer the genes to the cells might be a risk. Todays finding allays that concern, enabling researchers to move beyond immediately life-threatening illnesses, such as HIV and cancer, said Bruce Levine, a study author and researcher at the University of Pennsylvania.

We turned those cells into heat-seeking missiles directed against HIV-infected cells, said Levine, head of the Clinical Cell and Vaccine Production Facility at the Philadelphia universitys Perelman School of Medicine. What really surprised us was when we got those samples, not only could we detect the gene-modified cells but they appeared to be present at relatively stable levels.

Because the therapy has been found to work safely over a significant period of time, the designer cells should be considered a platform technology that can also be used by scientists researching other diseases besides HIV, Levine in a telephone interview.

Each patient in the study cited today received at least one transfusion of their own immune cells between 1998 and 2005. The T cells were designed to look for an HIV protein and kill any infected cells they encountered, before the virus has a chance to mature.

Its like a controlled burn, Levine said.

The U.S. Food and Drug Administration required the patients be followed for 15 years to see if any late-developing side- effects, such as cancer, might arise from the therapy. The patients were followed every year after their initial dose.

No gene therapy has been approved by the FDA. The field almost halted in 1999, when 18-year-old Jesse Gelsinger died within hours of being injected. Earlier, in a French trial, two of 10 patients acquired leukemia following gene therapy for Bubble Boy disease, or severe combined immunodeficiency.

Read the original:
Gene Therapy Safe in Decade-Long HIV Study That May Widen Use

BANGALORE, India, April 30, 2012 /PRNewswire/ --

I-SMART (Indian Society For Molecular Advanced Regenerative Technologies) a conglomerate of Indian scientists from DRDO, DST, Dr.Agarwal Hospitals, Manacells, Gene Research Foundation has organized the first Gene Therapy Convention to be held at Bangalore on May 2nd2012.

People who are interestedare welcome to contact Dr.Agarwal Hospitals for registrations. Address: Dr.Agarwal Hospitals15, Eagle ST, Bangalore 560025, Phone 080-22240736, 22240200, 22221242, mobile +91-9845010510, 9845039271, 9844202364 email generesearchfoundation@gmail.comThe conference will shed new light into the frontiers of medicine where patients can be addressed with healthy DNA from their own blood.

I-SMART Millenium Awards will be presented to the national heroes, Dr.V.K.Saraswat (Chief of DRDO), Sri Oscar Fernandes (MP), Sreesanth (Cricketeer), Pujya Swamy Chidanand Saraswati (Parmarth Niketan, Rishikesh) Dr. Ramasami (Sec DST),On May 2nd4 pm 2012, Bangalore.

DNA-Gene therapyuses peripheral blood from the patientsfinger with Mana (DNA Activator) to generate the patients own healthy or fetal DNA.This is the molecule responsible for creating aparticular human body and thus it can also repair and regenerate the respective aging person.Thus customization of medical technologies has made it possible to treat various conditions associated with diseases of the eye, neurological disorders, diabetes, hypertension, cancer etc.

The work on this line of treatment was initiated over 20 years backby Dr.Agarwal Hospitals and Gene Research Foundation, with the help of The Department of Science & Technology, Govt. of India. For over 6 years Mana DNA gene therapy and the Defence Research Development Organization have added value to medical science.They have used high tech instrumentation and microscopes to show DNA formation within seconds of one drop of patients blood and Mana (DNA activator) coming together.

Through Dr.Agarwal Hospitals this medication has been used on eye patients (most of them are associated with a general disease) with great success. Over the last 8 years and 12000 patients using the patients own blood (autologous) shows no side effects or allergic reactions. This has taken a new step into medical technologies by giving it customization of each individual patient and seems to be one single major breakthrough in making the treatment a success.

After two days of debate and discussion the first Gene Therapy Convention I-SMART 2012 will be brought into mass productionto reach out to soldiers on the front (DRDO),and the masses (DST, through Manacells. An expansion plan to the tune of 300 cr is required and investors are welcome to come in at this stage. Over 100cr will go into a high end research facility which will monitor the mass production as well as be open to other sources.

Read more:
Gene Therapy Convention I-SMART on May 2nd 2012, 4 PM to 7 PM, at Bangalore Under the Aegis of DRDO, DST, Dr.Agarwal ...

THURSDAY, April 19 (HealthDay News) -- Scientists say they've identified the first gene directly linked to the most common form of psoriasis, known as plaque psoriasis.

"We have searched for almost two decades to find a single gene linked to plaque psoriasis," study senior author Anne Bowcock, professor of genetics at Washington University School of Medicine in St. Louis, said in a university news release. "Individually, the rare mutations we have found likely confer a high risk for the disease, and we think they will be important in the search to find new, more effective treatments."

In conducting the study, researchers used cutting-edge DNA technology to uncover a rare mutation in the CARD14 gene in a large family of European descent with a high prevalence of plaque psoriasis and psoriatic arthritis. They also found the mutation among multiple members of an extended family from Taiwan who had the condition, which is characterized by dry, raised, red patches covered with silvery scales.

The genetic mutation was also identified in a 3-year-old girl with a severe and rare form of psoriasis, but in this case the condition was not inherited. She developed the condition after being treated for a staph infection.

"This is significant because it tells us that CARD14 alone plus an environmental trigger is enough to cause psoriasis," Bowcock explained. "You don't need anything else. This really highlights the importance of finding rare mutations for common diseases like psoriasis."

The findings suggest that immune cells are only a secondary cause of psoriasis. Skin defects, the researchers stated, are the main culprit behind the condition.

Noting that the family members studied who had psoriatic arthritis also had the CARD14 mutation, the study authors suggested the rare mutation may also be involved in at least one other form of psoriasis as well as a debilitating form of arthritis.

"Now, we have a much clearer picture of what is happening in psoriasis," Bowcock concluded. "And now with all kinds of new therapeutic targets that lie within the CARD14 pathway, the field is wide open."

The research was released online in advance of print publication in two separate papers in the May 4 issue of the American Journal of Human Genetics.

About 7.5 million Americans have psoriasis, the study authors noted.

See the rest here:
Gene Behind Psoriasis Identified, Researchers Say

Washington, April 14 : Researchers have discovered that changes in the gene expression of a key enzyme may contribute to high blood pressure and increase susceptibility to forming blood clots in pregnant women with preeclampsia.

These findings could provide clues to the best treatment approaches for high blood pressure and the formation of blood clots that can block blood flow to a pregnant woman's internal organs and lead to organ failure.

Virginia Commonwealth University School of Medicine researchers have been working to determine the root cause of preeclampsia on the molecular level and have now identified that epigenetic mechanisms may be at play.

Epigenetics refers to changes in gene expression that are mediated through mechanisms other than changes in the DNA sequence.

The VCU team reported that thromboxane synthase an important inflammatory enzyme is increased in the blood vessels of expectant mothers with preeclampsia.

The thromboxane synthase gene codes for this enzyme, which is involved in several processes including cardiovascular disease and stroke. This enzyme results in the synthesis of thromboxane, which increases blood pressure and causes blood clots.

"The present work is unique because it opens up a new concept as to the cause and subsequent consequences of preeclampsia relating to epigenetics," said corresponding author Scott W. Walsh, Ph.D., professor in the VCU Department of Obstetrics and Gynecology.

"It is the first study to show that epigenetic alterations in the blood vessels of the mother are related to preeclampsia," Walsh stated.

According to Walsh, one of the main epigenetic mechanisms is methylation of the DNA, which controls the expression of genes. The increase of this enzyme in the blood vessels is related to reduced DNA methylation and the infiltration of neutrophils into the blood vessels. Neutrophils are white blood cells that normally help fight infection.

In the future, Walsh said some potential treatments for preeclampsia may include inhibition of thromboxane synthase, blockade of thromboxane receptors or dietary supplementation with folate. He said that folate supplementation could increase methylation donors to protect against adverse changes in DNA methylation that affect expression of the thromboxane synthase enzyme.

The rest is here:
Changes in gene expression may cause high blood pressure in pregnancy

ScienceDaily (Apr. 15, 2012) The key to treating one of the most common types of human leukemia may lie within mutations in a gene called FLT3, according to new research led by physician-scientists at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center.

Published this week in the journal Nature, the work validates certain activating mutations in the FLT3 gene as targets for acute myeloid leukemia therapy -- a critically important finding for developing drugs.

"These mutations are critically important for the survival of leukemia cells that harbor them," said Neil Shah, MD, PhD, who led the research, and is co-leader of the Hematopoietic Malignancies Program at the Helen Diller Family Comprehensive Cancer Center at UCSF and the Edward S. Ageno Distinguished Professor of Hematology/Oncology. "Our results also identify drug-resistant mutations in FLT3 that represent high-value targets for future drug development, and will hopefully rekindle interest in developing potent FLT3 inhibitors for the treatment of acute myeloid leukemia."

The new work also suggests why a handful of older drugs developed to treat acute myeloid leukemia by targeting FTL3 have previously failed in clinical trials. The problem with these drugs was not lack of precision but of power -- they were aimed at the right target needed to stop the cancer, but most likely did not hit this target hard enough.

Patients in the future may be better served by therapies that involve combinations of multiple, more potent drugs that can suppress all drug-resistant forms of FLT3, said Shah, whose lab is working to identify such compounds and bring them to the clinic as quickly as possible.

Common and deadly form of cancer

Acute myeloid leukemia occurs when the precursors of our own blood cells become corrupted by mutations in their DNA. The mutant precursors then fail to produce several critical components of blood: white cells, which fight infections; red cells, which carry the blood's oxygen supply; and platelets, which clog vessels when they are cut and help minimize blood loss.

Instead, the mutant precursors give rise to leukemia cells, which accumulate in the bone marrow and bloodstream, crowding out the healthy blood components, and commonly lead to life-threatening infections, anemia, and bleeding.

Over the last several decades, the five-year survival for acute myeloid leukemia has not improved, even as better diagnostic tests, imaging techniques and treatments have driven down mortality for other forms of cancer. According to the National Cancer Institute, 1 in 256 Americans will be diagnosed with acute myeloid leukemia in their lifetime and today nearly four out of five people with the disease die within five years of their diagnosis.

The goal of therapy is to eliminate cancerous cells altogether from the bone marrow, and the discovery several years ago that many people with acute myeloid leukemia have activating mutations in the FTL3 gene, coupled with the relationship of these mutations to poor prognosis, led scientists to speculate that targeting this mutated gene might be an effective way to fight the cancer -- but only if the gene was critically important for the survival of leukemia cells.

Continued here:
Gene mutations play critically important role in acute myeloid leukemia; Promising development for new treatments

Public release date: 1-Apr-2012 [ | E-mail | Share ]

Contact: Bonnie Prescott bprescot@bidmc.harvard.edu 617-667-7306 Beth Israel Deaconess Medical Center

BOSTON -- In a finding that may challenge popular notions of body fat and health, researchers at Beth Israel Deaconess Medical Center (BIDMC) have shown how fat cells can protect the body against diabetes. The results may lead to a new therapeutic strategy for preventing and treating type 2 diabetes and obesity-related metabolic diseases, the authors say.

In the last decade, several research groups have shown that fat cells in people play a major role in controlling healthy blood sugar and insulin levels throughout the body. To do this crucial job, fat cells need a small portion of the sugars derived from food. Obesity often reduces the dedicated sugar transport molecules on fat cells, blocking the glucose from entering fat cells. As a result, the whole body becomes insulin resistant, and blood sugar rises, leading to diabetes.

The new study shows why glucose is so important to fat cells. The team discovered a new version of a gene inside fat cells that responds to sugar with a powerful systemic effect.

"If we change that one gene, that makes the animal more prone to or more protected from diabetes," said senior author Barbara Kahn MD, the George R. Minot Professor of Medicine at Harvard Medical School and Vice Chair of the Department of Medicine at BIDMC. "Many foods get converted into sugar, so there is no need to eat more sugar."

The paper is published online April 1 in the journal Nature. In the study, the BIDMC researchers pinpointed the fat gene and its effect in mouse models of human obesity and insulin resistance and reported supporting evidence from fat tissue samples from both lean and obese people.

"Two things were surprising first, that a lone gene could shift the metabolism of the fat cell so dramatically and then, that turning on this master switch selectively in adipose tissue is beneficial to the whole body," Kahn said. Twelve years ago, Kahn first demonstrated that fat cells are a master regulator of healthy levels of glucose and insulin in mice and require sugar to do the job.

"The general concept of fat as all bad is not true," said first author Mark Herman MD, an investigator in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Instructor of Medicine at Harvard Medical School (HMS). "Obesity is commonly associated with metabolic dysfunction that puts people at higher risk for diabetes, stroke and heart disease, but there is a large percentage of obese people who are metabolically healthy. We started with a mouse model that disassociates obesity from its adverse effects."

In the latest study, evidence suggests the newfound gene also may account for the protective effect of glucose uptake in human fat. German collaborators found more gene activity in people with greater insulin sensitivity, based on 123 adipose tissue samples from non-diabetic, glucose tolerant people. The fat gene activity also correlated highly with insulin sensitivity in obese, non-diabetic people, as measured in 38 fat samples by another pair of co-authors based in St. Louis.

Continue reading here:
Study finds protective gene in fat cells

Public release date: 15-Apr-2012 [ | E-mail | Share ]

Contact: Mount Sinai Press Office newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Through a groundbreaking new gene sequencing technology, researchers have demonstrated that the gene FLT3 is a valid therapeutic target in Acute Myeloid Leukemia, AML, one of the most common types of leukemia.

The technique, developed by Pacific Biosciences, allows for the rapid and comprehensive detection of gene mutations in patients with AML. The findings, published online April 15 in Nature, are a result of collaboration among scientists at the University of California, San Francisco, Pacific Biosciences and Mount Sinai School of Medicine. The discovery may help lead to the development of new drugs to treat AML.

"By sequencing the FLT3 gene in AML patients who have relapsed on therapy targeted against FLT3, we have determined that FLT3 is a valid therapeutic target, and this will certainly help us better understand the physiology of this type of leukemia in order to help us develop new therapies in the future," said Andrew Kasarskis, PhD, who performed the research with colleagues at Pacific Biosciences prior to becoming Vice Chair of the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine. "In addition, sequencing hundreds of single molecules of FLT3 allowed us to see drug resistance mutations at low frequency. This increased ability to see resistance will let us identify the problem of the resistance sooner in a patient's clinical course and help us take steps to address it."

Historically, DNA sequencing of individual molecules in a mixture has been difficult and time-consuming to achieve. However, Pacific Bioscience's single molecule real-time sequencer, the PacBio RS, identified mutations in the sequence reads obtained in a single run even at low levels, on the order of 1 to 3 percent of total sequence reads.

"This finding may have great utility for drug development, as we can begin to test drugs or a combination of drugs in patients with AML who have relapsed," added Kasarskis, who is also Co-Director of the Institute for Genomics and Multiscale Biology at Mount Sinai. "Furthermore, if we can find out when the drug resistant mutations occur exactly, clinicians may be able to prescribe another drug more quickly."

In this era of personalized medicine, many drugs have been developed to target the mutations in genes that cause cancer - in an effort to attack the cancer with minimal side effects. Oftentimes, patients develop resistance to drugs and new therapeutic strategies must be applied, so physicians use a second line drug, or combination of drugs, in an effort to target the new gene mutations that develop. Knowing exactly when this mutation and subsequent resistance occurs may be very helpful in identifying when new therapies may be prescribed.

In this study, researchers worked with eight leukemia patients who had participated in a clinical trial involving a compound known as AC220, the first clinically-active FLT3 inhibitor. All eight patients relapsed after first achieving deep remissions with AC220. The relapse indicated that patients had developed a resistance to the drug.

AML is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Treatment includes chemotherapy in order to eliminate leukemic cells and stem cell transplantation. However, through the identification of a valid therapeutic target (FLT3), scientists can begin to develop new and more effective therapies in the future.

Read more:
Scientists identify FLT3 gene as a valid therapeutic target in acute myeloid leukemia

Ingenuity iReport for Real-Time PCR, optimized for TaqMan Gene Expression Assays provides a quick and reliable way for bench biologists to understand gene expression data.

REDWOOD CITY, Calif., April 2, 2012 /CNW/ - Ingenuity Systems, a leading provider of information and analysis solutions for life science researchers, and Life Technologies Corporation (NASDAQ: LIFE - News) today announced Ingenuity iReport for Real-Time PCR optimized for TaqMan Gene Expression Assays. The new solution is an interactive report that extends analysis beyond Ct or fold-changes to an accurate and dynamic view of the biological information most relevant to a gene expression experiment.

Dr. Mikael Kubista , founder of TATAA Biocenter in Goteborg , Sweden , studies gene expression in single-cell astrocytes. "In our research, we have developed specific strategies for analyzing single-cell data and defining important sets of genes based on correlation between the genes' expressions as measured by qPCR. Uploading this data to iReport, we were able to immediately see the biology underlying our statistical results, and develop new hypotheses based on the differentially expressed pathways involved in our single cell experiments."

In contrast to time consuming manual searches for relevant publications and gene relationships, Ingenuity iReport for Real-Time PCR provides a more rapid and comprehensive understanding of pathways, processes, and diseases relevant to gene expression results. With its engaging and intuitive design, iReport for Real-Time PCR can be used by bench scientists to easily and accurately understand the biological meaning of their experiment within minutes. Peer-reviewed literature is cited throughout the report, allowing the underlying evidence to be easily accessed and referenced. iReport for Real-Time PCR has been optimized for several TaqMan Gene Expression assay formats, including TaqMan Array Card and OpenArray file types.

"Ingenuity iReport for Real-Time PCR is the perfect complement to our industry-leading PCR portfolio," said Chris Linthwaite, Head of Genetic Analysis, Life Technologies. "Our Real-Time PCR products produce data that is highly sensitive and specific with a broad dynamic range and at a cost-effective price per data point. Integrating iReport into our portfolio will enable our customers to accelerate the pace of scientific discovery quickly connecting data to biological meaning."

"Life Technologies is focused on creating a complete user experience for their PCR customers," said Jake Leschly, CEO of Ingenuity Systems. "With iReport for Real-Time PCR we have designed a revolutionary product that will help researchers identify relevant biology from gene expression experiments and we have gone to great lengths to design a fully integrated marketing, e-commerce and customer support experience to ensure that the combined Real-Time PCR iReport experience is as seamless and easy as the products themselves."

Free iReport for a Limited Time

To learn more about Ingenuity iReport for Real-Time PCR or to receive a free report, please go to http://www.lifetechnologies.com/ireport. Additional product information will also be available from Ingenuity (booth 1602) and Life Technologies (booth 4419) at the American Association of Cancer Research (AACR) meeting, March 31-April 4th, in Chicago , Illinois.

About Ingenuity Systems

Ingenuity Systems is a leading provider of information and analysis solutions for life science researchers, computational biologists and bioinformaticists, and life science industry suppliers. For more information visit: http://www.ingenuity.com.

See the original post here:
Ingenuity Systems and Life Technologies Introduce Complete End-to-End Solution for Real-Time PCR Gene Expression ...

ScienceDaily (Apr. 1, 2012) University of North Carolina at Chapel Hill researchers working as part of the International Cystic Fibrosis Consortium have discovered several regions of the genome that may predispose cystic fibrosis (CF) patients to develop an intestinal blockage while still in the uterus.

A report of this international study appears online April 1, 2012 in the journal Nature Genetics. It was the work of the North America CF Gene Modifier Consortium, which brought together dozens of investigators from the United States, Canada, and from France, to identify genetic variations that could be linked with meconium ileus (MI), an intestinal obstruction that usually requires emergency surgery for treatment, and can result in a substantially increased rate of serious health problems.

MI affects roughly 15-20 percent of all patients with CF, a genetic condition that causes scarring throughout the body, especially the lungs and pancreas. Though every CF patient carries mutations in both copies of the same gene -- coding for a protein called cystic fibrosis transmembrane conductance regulator, or CFTR -- symptoms can vary widely from patient to patient.

The genome-wide association study (GWAS) of more than 3,700 CF patients identified non-CFTR genetic variants in the cell membrane that separates the interior of cells from the outside environment. More specifically, the variants involved genes responsible for ion transport in the lower end of the small intestine.

"These variants involve cells in the small intestine that predispose CF patients to develop MI while still in the womb," said one of the senior study authors Michael Knowles, MD, professor of pulmonary and critical care medicine at UNC and a member of UNC's Cystic Fibrosis-Pulmonary Research and Treatment Center.

"The discovery provides new understanding of the pathogenic mechanisms underlying MI. In addition, it offers the possibility of developing therapies to intervene in utero," Knowles said. "Further, it provides molecular insight into the role of genetic variation in ion transporters in CF, which may be applicable to more commonly, and severely, involved organs such as the lungs."

Other UNC study coauthors are Wanda K. O'Neal, Rhonda G. Pace, Jaclyn R. Stonebraker, Sally D. Wood, and Fred A. Wright. In the U.S., the study was funded by the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Cystic Fibrosis Foundation.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

Read this article:
Gene variations linked to intestinal blockage in newborns with cystic fibrosis

Rice University and IBM today have announced a partnership to build the first award-winning IBM Blue Gene supercomputer in Texas. Rice also announced a related collaboration agreement with the University of Sao Paulo in Brazil to initiate the shared administration and use of the Blue Gene supercomputer, which allows both institutions to share the benefits of the new computing resource.

Rice faculty will use the Blue Gene to further their own research and to collaborate with academic and industry partners on a broad range of science and engineering questions related to energy, geophysics, basic life sciences, cancer research, personalized medicine and more.

The collaborative agreement securing Brazil's share of time on Rice's Blue Gene was signed in Sao Paulo March 27 by a delegation that included Rice President David Leebron and USP President Joo Grandino Rodas. Leebron is traveling with a delegation led by Houston Mayor Annise Parker. The delegation includes Rice Provost George McLendon, Greater Houston Partnership (GHP) President and CEO Jeff Moseley and other GHP members.

"Collaboration and partnership have a unique place in Rice's history as a pre-eminent research university, and it is fitting that Rice begins its second century with two innovative partnerships that highlight the university's commitments to expanding our international reach, strengthening our research and building stronger ties with our home city," Leebron said.

USP is Brazil's largest institution of higher education and research, and Rodas said the agreement represents an important bond between Rice and USP. "The joint utilization of the supercomputer by Rice University and USP, much more than a simple sharing of high-tech equipment, means the strength of an effective partnership between both universities," he said.

Mayor Parker, a 1978 Rice alumna, said, "When I was at Rice, it looked inward. Today it looks outward through this agreement. It strengthens not only Rice University but also the city of Houston."

Rice's new P series Blue Gene supercomputer, which has yet to be named, is slated to become operational in May. It is based on IBM's POWER processor technology, which was developed in part at the company's Austin, Texas labs. Rice and IBM shared the cost of the system.

"High-performance computers like the IBM Blue Gene/P are critical in virtually every discipline of science and engineering, and we are grateful for IBM's help in bringing this resource to Rice," McLendon said. "For individual faculty, the supercomputer will open the door to new areas of research. The Blue Gene also opens doors for Rice as the university seeks to establish institutional relationships both in our home city and with critical international partners like USP."

Unlike the typical desktop or laptop computer, which have a single microprocessor, supercomputers typically contain thousands of processors. This makes them ideal for scientists who study complex problems, because jobs can be divided among all the processors and run in a matter of seconds rather than weeks or months. Supercomputers are used to simulate things that cannot be reproduced in a laboratory -- like Earth's climate or the collision of galaxies -- and to examine vast databases like those used to map underground oil reservoirs or to develop personalized medical treatments.

USP officials said they expect their faculty to use the supercomputer for research ranging from astronomy and weather prediction to particle physics and biotechnology.

View post:
Rice, IBM partner to build Texas’ first Blue Gene supercomputer

29-03-2012 12:24 More LXBN TV interviews at: While talk this week of course focuses on the oral arguments in the Affordable Care Act case, the Supreme Court last week ruled in a very important and influential intellectual property case. In Mayo Collaborative Services v. Prometheus Laboratories, Inc., the court ruled that the patent Prometheus had obtained for correlations between blood test results and patient health is not eligible for a patent because it incorporates laws of nature. Not only does this have a big impact on the medical community, but also another major case—the Myriad "gene patenting" case. To explain the background of Mayo v. Prometheus, whether or not these types of patents slow medical research and what this means for the Myriad case, we bring in Foley & Lardner Partner Antoinette Konski, who has covered this case exceptionally on the Personalized Medicine Bulletin--

Read more here:
Mayo v. Prometheus and Its Impact on Myriad "Gene Patenting" Case—Antoinette Konski - Video

OMAHA, Neb.--(BUSINESS WIRE)--

Transgenomic, Inc. (OTCBB: TBIO.OB - News) today announced that Jeana DaRe, Ph.D., Assistant CLIA Laboratory Director at Transgenomic, presented clinical findings from patients tested for nuclear mitochondrial disorders using Transgenomics NuclearMitome Test on Thursday, March 29, at the 2012 Annual Meeting of the American College of Medical Genetics (ACMG) in Charlotte, North Carolina. The discussion, titled Clinical re-sequencing of over 410 genes to diagnose mitochondrial disorders included details of both the technical performance of the NuclearMitome Test as well as the wide variety of clinically revealing results discovered through its use. The NuclearMitome Test employs next-generation sequencing technology to identify mutations in 448 genes, and represents the most comprehensive genetic test available for mitochondrial disorders.

In her presentation, Dr. DaRe highlighted two case studies. In both cases, patients achieved a definitive diagnosis through the identification of genetic mutations far outside the normal spectrum of genetic testing. These results concluded the patients diagnostic odysseys, which had encompassed wide-ranging genetic and non-genetic tests as well as consultation with various medical specialties, all of which had failed to pinpoint the underlying disease. These results are a typical occurrence in patients sent for NuclearMitome testing.

The NuclearMitome Test is a cutting-edge technology that is reshaping the process for accurately diagnosing and effectively treating patients with mitochondrial disorders, said Craig Tuttle, CEO of Transgenomic. Since its launch in June 2011, clinicians have embraced this test as a way to simultaneously assay the hundreds of genes relevant to mitochondrial-based developmental disorders and achieve otherwise impossible diagnoses. The NuclearMitome test is rapidly becoming an important asset for the medical and patient communities and for Transgenomic.

About Mitochondrial Diseases

Mitochondrial diseases are the most common metabolic diseases of childhood with an estimated frequency of 1 in 2000 births. They are characterized by multi-organ involvement, particularly neuromuscular symptoms, and often follow a rapidly progressive course. The variability in clinical presentation makes diagnosis tremendously challenging, as it traditionally relies on often-inconclusive enzymatic analyses that do not pinpoint the underlying molecular defect. Knowledge of the specific cause of disease can be important for developing personalized treatment strategies.

About Transgenomic, Inc.

Transgenomic, Inc. (www.transgenomic.com) is a global biotechnology company advancing personalized medicine in cancer and inherited diseases through its proprietary molecular technologies and world-class clinical and research services. The company has three complementary business divisions: Transgenomic Pharmacogenomic Services is a contract research laboratory that specializes in supporting all phases of pre-clinical and clinical trials for oncology drugs in development. Transgenomic Clinical Laboratories specializes in molecular diagnostics for cardiology, neurology, mitochondrial disorders, and oncology. Transgenomic Diagnostic Tools produces equipment, reagents, and other consumables that empower clinical and research applications in molecular testing and cytogenetics. Transgenomic believes there is significant opportunity for continued growth across all three businesses by leveraging their synergistic capabilities, technologies, and expertise. The company actively develops and acquires new technology and other intellectual property that strengthen its leadership in personalized medicine.

Forward-Looking Statements

Certain statements in this press release constitute forward-looking statements of Transgenomic within the meaning of the Private Securities Litigation Reform Act of 1995, which involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Forward-looking statements include, but are not limited to, those with respect to management's current views and estimates of future economic circumstances, industry conditions, company performance and financial results, including the ability of the Company to grow its involvement in the diagnostic products and services markets. The known risks, uncertainties and other factors affecting these forward-looking statements are described from time to time in Transgenomic's filings with the Securities and Exchange Commission. Any change in such factors, risks and uncertainties may cause the actual results, events and performance to differ materially from those referred to in such statements. Accordingly, the Company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 with respect to all statements contained in this press release. All information in this press release is as of the date of the release and Transgenomic does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

View post:
Transgenomic, Inc. Announces Presentation of Results from 448-Gene NuclearMitome Test in 78 Patients at the 2012 ...

IBM Inks Blue Gene Supercomputer Deals With Rice, Rutgers Universities ( Page 1 of 3 )

IBM has had a busy week with academia, announcing partnerships with both Rice University and Rutgers University to advance supercomputing at their institutions and in their home states of Texas and New Jersey, respectively.

On March 30, IBM (NYSE: IBM) and Rice University announced a partnership to build the first IBM Blue Gene supercomputer in Texas. Rice also announced a related collaboration agreement with the University of Sao Paulo (USP) in Brazil to initiate the shared administration and use of the Blue Gene supercomputer, which allows both institutions to share the benefits of the new computing resource.

IBM officials said Rice faculty will use the Blue Gene to further their own research and to collaborate with academic and industry partners on a broad range of science and engineering questions related to energy, geophysics, basic life sciences, cancer research, personalized medicine and more.

The collaborative agreement securing Brazil's share of time on Rice's Blue Gene was signed in Sao Paulo March 27 by a delegation that included Rice President David Leebron and USP President Joao Grandino Rodas. Leebron is traveling with a delegation led by Houston Mayor Annise Parker. The delegation includes Rice Provost George McLendon, Greater Houston Partnership (GHP) President and CEO Jeff Moseley and other GHP members.

"Collaboration and partnership have a unique place in Rice's history as a pre-eminent research university, and it is fitting that Rice begins its second century with two innovative partnerships that highlight the university's commitments to expanding our international reach, strengthening our research and building stronger ties with our home city," Leebron said in a statement.

USP is Brazil's largest institution of higher education and research, and Rodas said the agreement represents an important bond between Rice and USP. "The joint utilization of the supercomputer by Rice University and USP, much more than a simple sharing of high-tech equipment, means the strength of an effective partnership between both universities," he said.

Mayor Parker, a 1978 Rice alumna, said, "When I was at Rice, it looked inward. Today, it looks outward through this agreement. It strengthens not only Rice University but also the city of Houston."

Rice's new Blue Gene supercomputer, which has yet to be named, is slated to become operational in May. It is based on IBM's POWER processor technology, which was developed in part at the company's Austin, Texas, labs. Rice and IBM shared the cost of the system.

Next: High-Performance Computers Are Crucial in Science, Engineering >>

Read the rest here:
IBM Inks Blue Gene Supercomputer Deals With Rice and Rutgers Universities

(Ivanhoe Newswire)-- A ravenous appetite may be what causes many overweight people to be obese. Researchers have found a mutation in a single gene is responsible for the inability of neurons to effectively send out appetite suppressing signals from the body to the correct area of the brain.

A study suggests that there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.

Researchers found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to adequately pass leptin and insulin chemical signals through the brain. In humans, these hormones are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues.

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," Baoji Xu, Ph.D., study's senior investigator, an associate professor of pharmacology and physiology at Georgetown, was quoted as saying.

"This discovery may open up novel strategies to help the brain control body weight," he said.

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons.

Xu also found that the mice with the same Bdnf mutation grew to be severely obese.

Other researchers began to look at the Bdnf gene in humans, and large-scale genome-wide association studies showed Bdnf gene variants are, were also linked to obesity.

However, until this study, no one has been able to describe exactly how BDNF controls body weight.

Xu's data shows that both leptin and insulin stimulate synthesis of BDNF in neuronal dendrites in order to move their chemical message from one neuron to another through synapses. The intent is to keep the leptin and insulin chemical signals moving along the neuronal pathway to the correct brain locations, where the hormones will turn on a program that suppresses appetite.

The rest is here:
Single Gene Could Play Role in Obesity

HOUSTON, March 30, 2012 /PRNewswire/ --Rice University and IBM (NYSE: IBM) today announced a partnership to build the first award-winning IBM Blue Gene supercomputer in Texas. Rice also announced a related collaboration agreement with the University of Sao Paulo (USP) in Brazil to initiate the shared administration and use of the Blue Gene supercomputer, which allows both institutions to share the benefits of the new computing resource.

(Logo: http://photos.prnewswire.com/prnh/20090416/IBMLOGO )

Rice faculty will use the Blue Gene to further their own research and to collaborate with academic and industry partners on a broad range of science and engineering questions related to energy, geophysics, basic life sciences, cancer research, personalized medicine and more.

The collaborative agreement securing Brazil's share of time on Rice's Blue Gene was signed in Sao Paulo March 27 by a delegation that included Rice President David Leebron and USP President Joao Grandino Rodas. Leebron is traveling with a delegation led by Houston Mayor Annise Parker. The delegation includes Rice Provost George McLendon, Greater Houston Partnership (GHP) President and CEO Jeff Moseley and other GHP members.

"Collaboration and partnership have a unique place in Rice's history as a pre-eminent research university, and it is fitting that Rice begins its second century with two innovative partnerships that highlight the university's commitments to expanding our international reach, strengthening our research and building stronger ties with our home city," Leebron said.

USP is Brazil's largest institution of higher education and research, and Rodas said the agreement represents an important bond between Rice and USP. "The joint utilization of the supercomputer by Rice University and USP, much more than a simple sharing of high-tech equipment, means the strength of an effective partnership between both universities," he said.

Mayor Parker, a 1978 Rice alumna, said, "When I was at Rice, it looked inward. Today it looks outward through this agreement. It strengthens not only Rice University but also the city of Houston."

Rice's new Blue Gene supercomputer, which has yet to be named, is slated to become operational in May. It is based on IBM's POWER processor technology, which was developed in part at the company's Austin, Texas labs. Rice and IBM shared the cost of the system.

"High-performance computers like the IBM Blue Gene/P are critical in virtually every discipline of science and engineering, and we are grateful for IBM's help in bringing this resource to Rice," McLendon said. "For individual faculty, the supercomputer will open the door to new areas of research. The Blue Gene also opens doors for Rice as the university seeks to establish institutional relationships both in our home city and with critical international partners like USP."

Unlike the typical desktop or laptop computer, which have a single microprocessor, supercomputers typically contain thousands of processors. This makes them ideal for scientists who study complex problems, because jobs can be divided among all the processors and run in a matter of seconds rather than weeks or months. Supercomputers are used to simulate things that cannot be reproduced in a laboratory -- like Earth's climate or the collision of galaxies -- and to examine vast databases like those used to map underground oil reservoirs or to develop personalized medical treatments.

Follow this link:
Rice University, IBM Partner to Bring First Blue Gene Supercomputer to Texas

Worried about cybertheft? Thats so 20th century. Tonights NOVA (8 p.m., PBS) explores a brave new world thats now upon us: the era of the genetic code and the powerful and potentially dangerous information it can reveal.

Our genetic blueprints can become the starting point for aggressive preventive medicine, allowing doctors to understand a cancers genome and learn how to attack it. We may soon be able to pinpoint medications to particular genes and diseases, methods that will make the medical carpet bombing of chemotherapy seem crude by comparison. If were going to switch to prevention, then your own genome sequence may be one of the most critical tools you could imagine, says Francis Collins, director of the National Institutes of Health.

But knowledge of peoples genetic makeup and defects could lead to a kind of DNA-based discrimination. Will insurance companies and potential employers start to shun people whose DNA pinpoints expensive maladies? Will it lead to a master-race-breeding mentality, affecting how individuals choose a potential spouse? Will political candidates be compelled to reveal their genetic code the way they now must release their tax statements?

Sequencing an individuals human genome used to be the stuff of science fiction. And until quite recently its prohibitive price tag (upward of $350,000) kept it out of reach. Now companies can do it for less than $1,000 and the price continues to fall, bringing this powerful information within reach of those who could help you, or spy upon your innermost vulnerabilities.

Whitechapel (9 p.m., BBC America), the stylish British detective series where criminals always hearken back to the murderous misdeeds of history, returns for a third season.

Tonights other highlights

An expired license trips up a trip down the aisle on the season finale of Whitney (7 p.m., NBC).

Two hours of live performances on American Idol (7 p.m., Fox).

Americas Next Top Model: British Invasion (8 p.m., CW) travels to Canada. Banality without borders.

Woodys career path could turn on the determination of a victims cause of death on Psych (9 p.m., USA).

See the original post here:
Gene genie out of the bottle

By Bloomberg News

An experimental drug from Sanofi and Regeneron Pharmaceuticals Inc. lowered patients so-called bad cholesterol by as much as 72 percent on top of Lipitor in a company-funded study.

(Last year, French drug maker Sanofi bought Genzyme Corp. of Cambridge for $20.1 billion.)

The medicine, one in a class of drugs targeting the PCSK9 gene, reduced patients average LDL cholesterol levels to as little as 34 milligrams per deciliter after 12 weeks in the mid- stage study, presented today at the American College of Cardiology meeting in Chicago. Less than 100 mg/dL is considered optimal for LDL, according to the Mayo Clinic.

Its a wow study, said James McKenney, the trials lead investigator and chief executive officer of National Clinical Research, a Virginia-based company that runs studies. Instantly youre seeing all those patients you could not get to the level youd like for them to be at, now you have a medicine that unquestionably can.

About 25 percent of US adults 45 and over take cholesterol-lowering statins, according to the National Center for Health Statistics. Statins include pills such as Pfizer Inc.s Lipitor, the worlds best-selling medicine in 2010 with revenue of $10.7 billion. Almost a third of statin users dont get enough of a benefit, leaving them more vulnerable to heart disease and in need of additional therapy, McKenney said in a telephone interview.

The 183-patient trial, funded by Paris-based Sanofi and Tarrytown, N.Y.-based Regeneron, produced results reminiscent of the cholesterol-lowering advances achieved by statins two to three decades ago, McKenney said. Patients for whom statins work can see their cholesterol reduced by as much as 50 percent, lowering heart risks, he said.

Amgen Inc., in Thousand Oaks, Calif., New York-based Pfizer, and Whitehouse Station, N.J.-based Merck & Co. are also developing treatments targeting PCSK9, said Chris Raymond, an analyst with Robert W. Baird & Co. in Chicago. The gene creates a protein that disrupts the ability of liver cells to remove bad cholesterol from blood, enabling it to accumulate.

The study presented today evaluated five doses of Regeneron and Sanofis medicine, dubbed REGN727 or SAR236553, compared with a placebo. It found that 50 milligrams of the drug injected once every two weeks lowered LDL cholesterol by 40 percent, while 300 milligrams dosed every four weeks reduced LDL by 48 percent. The most-effective dose was 150 milligrams injected every two weeks, shown to lower LDL by 72 percent.

Patients took Lipitor at doses of 10, 20, or 40 milligrams for at least six weeks before starting the study, and still had LDL levels higher than 100 mg/dL. All groups continued taking Lipitor throughout the trial. Those on placebo -- Lipitor with no additional therapy -- had an LDL decline of 5 percent.

See original here:
Sanofi-Regeneron drug lowers cholesterol up to 72 percent in study

ScienceDaily (Mar. 27, 2012) A team of researchers led by scientists at Weill Cornell Medical College has designed what appears to be a powerful gene therapy strategy that can treat both beta-thalassemia disease and sickle cell anemia. They have also developed a test to predict patient response before treatment.

This study's findings, published in PLoS ONE, represents a new approach to treating these related, and serious, red blood cells disorders, say the investigators.

"This gene therapy technique has the potential to cure many patients, especially if we prescreen them to predict their response using just a few of their cells in a test tube," says the study's lead investigator, Dr. Stefano Rivella, Ph.D., an associate professor of genetic medicine at Weill Cornell Medical College. He led a team of 17 researchers in three countries.

Dr. Rivella says this is the first time investigators have been able to correlate the outcome of transferring a healthy beta-globin gene into diseased cells with increased production of normal hemoglobin -- which has long been a barrier to effective treatment of these disease.

So far, only one patient in France has been treated with gene therapy for beta thalassemia, and Dr. Rivella and his colleagues believe the new treatment they developed will be a significant improvement. No known patient has received gene therapy yet to treat sickle cell anemia.

A Fresh Approach to Gene Therapy

Beta-thalassemia is an inherited disease caused by defects in the beta-globin gene. This gene produces an essential part of the hemoglobin protein, which, in the form of red blood cells, carries life-sustaining oxygen throughout the body.

The new gene transfer technique developed by Dr. Rivella and his colleagues ensures that the beta-globin gene that is delivered will be active, and that it will also provide more curative beta-globin protein. "Since the defect in thalassemia is lack of production of beta-globin protein in red blood cells, this is very important," Dr. Rivella says.

The researchers achieved this advance by hooking an "ankyrin insulator" to the beta-globin gene that is carried by a lentivirus vector. During the gene transfer, this vector would be inserted into bone marrow stem cells taken from patients, and then delivered back via a bone marrow transplant. The stem cells would then produce healthy beta-globin protein and hemoglobin.

This ankyrin insulator achieves two goals. First, it protects delivery of the normal beta-globin gene. "In many gene therapy applications, a curative gene is introduced into the cells of patients in an indiscriminate fashion," Dr. Rivella explains. "The gene lands randomly in the genome of the patient, but where it lands is very important because not all regions of the genome are the same." For example, some therapeutic genes may land in an area of the genome that is normally silenced -- meaning the genes in this area are not expressed. "The role of ankyrin insulator is to create an active area in the genome where the new gene can work efficiently no matter where it lands," Dr. Rivella says. He adds that the small insulator used in his vector should eliminate the kind of side effects seen in the French patient treated with beta-thalassemia gene therapy.

Link:
New gene therapy approach developed for red blood cell disorders

TAMPA, Fla.--(BUSINESS WIRE)--

Innovaro, Inc (NYSE Amex: INV), The Innovation Solutions Company, is pleased to announce that its client Inven2, the technology transfer office at Oslo University Hospital and University of Oslo, has entered into an exclusive licensing agreement with Oxford Gene Technology (OGT) for 12 highly promising colorectal cancer tissue biomarkers through Innovaros Pharmalicensing Partnering Search & Profiling division.

The exclusive license allows OGT to commercialize any resulting test developed using these biomarkers and to sublicense the markers to other parties. The DNA methylation biomarkers were developed in the laboratory of Professor Ragnhild A. Lothe, in the department of Cancer Prevention, the Norwegian Radium Hospital, part of the Oslo University Hospital.

OGT has validated the results obtained in Professor Lothes laboratory showing sensitivity of 93% and specificity of 90% when using tissue biopsies. Further work investigating the efficacy of these biomarkers in blood and fecal samples is ongoing.

We fully support the collaboration with Oxford Gene Technology to develop a new method of detecting colorectal cancer using these biomarkers. This agreement demonstrates the importance of industry and academic collaboration in turning scientific excellence into products that address medical needs, commented Benedicte Bakke, Business Development Manager at Inven2. The Innovaro Pharmalicensing Profiling service was able to bring this high quality potential partner to our attention that we may not otherwise have met.

This licensing agreement gives OGT exclusive access to genetic markers which are associated with colorectal cancer, stated Mike Evans, CEO of OGT. We believe that developing tests that include these genetic markers will permit the earlier identification of patients at risk of this disease and allow for more timely diagnosis and clinical interventions. He added, The higher specificity of this new panel of markers could prove a more robust screening tool than the tests currently used, while eventually lowering overall costs, which would be of significant benefit for both patients and the clinicians using them.

We are delighted that Inven2 was able to identify Oxford Gene Technology as an appropriate candidate partner, using Innovaro Pharmalicensings Profiling service, clearly leading to this important licensing agreement, confirmed Mark McBride, Senior VP Fulfilment Services, Innovaro, Inc. This agreement also demonstrates the effectiveness of Innovaros Pharmalicensing Profiling service for the life sciences alongside our already well recognized proficiency in Partnering Search services.

About Inven2

Inven2 is the Technology Transfer Office for the University of Oslo and Oslo University Hospital, Norway's largest and leading university and hospital representing pioneering research. Inven2 is the largest contributor in Norway within the field of commercialization of research across Life Sciences. For more information on Inven2, please visit its website at http://www.inven2.com.

About Oxford Gene Technology

See the original post here:
Innovaro Announces Completion of Licensing Agreement between Inven2 and Oxford Gene Technology