Category Archives: Gene Medicine

PUBLIC RELEASE DATE:

3-Nov-2014

Contact: Allison Hydzik hydzikam@upmc.edu 412-647-9975 University of Pittsburgh Schools of the Health Sciences @UPMCnews

PITTSBURGH, Nov. 3, 2014 Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against the development of colorectal cancer by inducing cell suicide pathways in intestinal stem cells that carry a certain mutated and dysfunctional gene, according to a new study led by researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine. The findings were published online today in the Proceedings of the National Academy of Sciences.

Scientists have long known from animal studies and clinical trials that use of NSAIDs, such as aspirin and ibuprofen, lowers the risk of developing intestinal polyps, which can transform into colon cancer. But they have not known why, said senior investigator Lin Zhang, Ph.D., associate professor, Department of Pharmacology and Chemical Biology, Pitt School of Medicine, and UPCI, a partner with UPMC CancerCenter.

"Our study identifies a biochemical mechanism that could explain how this preventive effect occurs," he said. "These findings could help us design new drugs to prevent colorectal cancer, which is the third leading cause of cancer-related deaths in the country."

The research team performed experiments in animal models and examined tumor samples from patients who had taken NSAIDs and those who hadn't. They found that NSAIDs activate the so-called death receptor pathway, which selectively triggers a suicide program in intestinal stem cells that have a mutation in the APC gene that renders the cells dysfunctional. Healthy cells lack the mutation, so NSAIDs cause them no harm. In that manner, the drugs instigate the early auto-destruction of cells that could lead to precancerous polyps and tumors.

"We want to use our new understanding of this mechanism as a starting point to design better drugs and effective cancer prevention strategies for those at high risk of colon cancer," Dr. Zhang said. "Ideally, we could harness the tumor-killing traits of NSAIDs and avoid possible side effects that can occur with their chronic use, such as gastrointestinal bleeding and ulcers."

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The research team included lead author Brian Leibowitz, Ph.D., and Jian Yu, Ph.D., of UPCI and the Pitt's Department of Pathology, as well as others from UPCI and Pitt School of Medicine; Sichuan University, China; INCELL Corp, San Antonio, Texas; and Indiana University School of Medicine. The project was funded by National Institutes of Health grants CA106348, CA121105, CA172136, CA129829 and DK085570, and the American Cancer Society.

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NSAIDs prevent colon cancer by inducing death of intestinal stem cells that have mutation

Published November 04, 2014

Workers prepare traditional Chinese herbal medicines at Beijing's Capital Medical University Traditional Chinese Medicine Hospital May 25, 2011. REUTERS/David Gray

Traditional Chinese medicine teaches that some people have hot constitutions, making them prone to fever and inflammation in parts of the body, while others tend to have cold body parts and get chills.

Such Eastern-rooted ideas have been developed over thousands of years of experience with patients. But they arent backed up by much scientific data.

Now researchers in some the most highly respected universities in China, and increasingly in Europe and the U.S., are wedding Western techniques for analyzing complex biological systems to the Chinese notion of seeing the body as a networked whole. The idea is to study how genes or proteins interact throughout the body as a disease develops, rather than to examine single genes or molecules.

Traditional Chinese medicine views disease as complete a pattern as possible, says Jennifer Wan, a professor in the school of biological sciences at the University of Hong Kong who studies traditional Chinese medicine, or TCM. Western medicine tends to view events or individuals as discrete particles. But one gene or biological marker alone typically doesnt yield comprehensive understanding of disease, she says.

To reach these goals, the overall quality of research on traditional Chinese medicine must improve. With studies of Chinese herbal remedies, for instance, rarely are scientists expected to provide authentication of herbs theyre studying, which makes it difficult to know whats really in the concoctions. This hurdle also makes it harder for other scientists to replicate the findings, says Qihe Xu, a professor in renal medicine at Kings College London. Dr. Xu served as the coordinator of a recent 200-scientist consortium to study good practices for studying traditional Chinese medicine, dubbed GP-TCM.

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Researchers push to back traditional Chinese medicine with more data

An Ottawa hospital is challenging the legality of gene patents that hamper the ability of doctors to freely screen for potentially deadly genetic diseases without fear of being sued forpatent violations.

On Monday, the Childrens Hospital of Eastern Ontario (CHEO) started a legal process in Federal Court that could decide if human genes can be patented in Canada.

"Its about whether Canadian hospitals can provide genetic testing to Canadian patients and really give them the top quality of care," said Richard Gold, a lawyer and intellectual property expert at McGill University in Montreal, who is advising the hospital pro bono.

Currently, some genetic tests cant be done in Canada because U.S. companies hold patents on the tests and the genes and have threatened legal action if the patents are violated by doing the tests in Canada, rather than the U.S.

The U.S. Supreme Court ruled last year that naturallyoccurring human genes cant be patented and threw out patents held by Myriad Genetics Inc. to look for mutations on the BRCA 1 and BRCA 2 genes associated with much greater risks of breast and ovarian cancer,including a mutation that actorAngelina Jolie revealed she inherited.

CHEOs case centres on patents for genes associated with long QT syndrome, an inherited heart rhythm disorder that typically presents for the first time as a fainting spell or seizure during exercise or tragically in sudden death, said Gail Graham, head of medicine genetics at the Ottawa hospital.

"Genetic technology is just exploding. It's increasingly embedding itself at the heart of medicine," Graham said.

Long QT syndrome is treatable, but it often results in sudden death of a young person. With genetic screening, doctors aim to treat it before tragedy strikes.

The hospital is not allowed to screen for genes associatedwith long QT syndrome because a U.S. company has patented the test and the genes.

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U.S. Gene Patents: Patient Care Stymied In Canada, Hospital Claims

Can genes be patented? An Ottawa hospital filed a legal challenge in federal court on Monday that will bring that thorny question to Canada.

The U.S. Supreme Court ruled in 2013 that it isnt possible to patent naturally occurring genes because they are products of nature, throwing out patents held by the company Myriad Genetics on the BRCA1 and BRCA2 genes. Carriers of harmful mutations in those genes have an increased risk of breast and ovarian cancer, and testing for it became cheaper and more widely available within hours of the U.S. ruling.

But the issue has not been considered by Canadian courts. Mondays legal case, brought by the Childrens Hospital of Eastern Ontario (CHEO), deals with five patents held in Canada by the University of Utah, Genzyme Genetics and Yale University on genes and tests for an inherited cardiac condition called Long QT syndrome.

The disorder can cause fainting, seizures and sudden death. Patients who are identified before they show symptoms can be treated with drugs and, in some cases, medical implants.

Long QT is just one of thousands and thousands of genetic conditions. So (the case) is specifically about Long QT, but really its a much broader issue about the future of medicine and delivering on the potential of recent technology, said Alex Munter, president and CEO of the hospital.

Yet proponents of gene patents have long argued that invalidating them will stifle medical innovation, since patents are meant to act as an incentive to create new and better technologies.

CHEO filed the suit Monday morning; the University of Utah and the other defendants have not yet had a chance to respond.

Currently, if an Ontario doctor suspects that their patient has Long QT syndrome, the diagnosis includes sending a blood sample to a lab in the U.S.

The two-tier test currently costs approximately $4,500 (U.S.) per person, CHEO estimates, whereas researchers at the hospital believe they could administer the same process in-house for about half the cost.

The collective impact (of this case) could easily be in the orders of millions of dollars for the healthcare system, said Gail Graham, a clinical geneticist at the hospital.

Originally posted here:
Gene patent lawsuit aims to clear up confusion in Canada

By Sheryl Ubelacker, The Canadian Press Published Monday, November 3, 2014 12:29PM EST Last Updated Monday, November 3, 2014 12:35PM EST

TORONTO -- A Canadian hospital is launching a court challenge with the ultimate goal of invalidating patents on human genes, saying such protection can adversely affect the health of patients and boost the country's health-care costs.

Lawyers for the Children's Hospital of Eastern Ontario, or CHEO, were in the process early Monday of filing the challenge in Federal Court in Ottawa, arguing that genes and other segments of the human genome should not be subject to patents for commercial or any other purposes.

"The core position really is that no one should be able to patent human DNA," said Alex Munter, president and CEO of the Ottawa-based CHEO. "It would be like patenting water or air."

Companies or other institutions that hold patents on genes or snippets of DNA and own the rights to diagnostic tests developed using that genetic information have a monopoly on what can be done with the information.

Last year, the U.S. Supreme Court ruled that naturally occurring human DNA cannot be patented, siding with advocates who argued that the multibillion-dollar biotechnology industry should not have exclusive control over genetic information found inside the human body.

But in Canada, there has been no similar court challenge to the country's Patent Act -- and hence no ruling, said Richard Gold, a professor of law at McGill University in Montreal.

"There's considerable lack of clarity in Canada, especially after the U.S. decision about exactly what can be patented," said Gold, who is consulting pro bono on the case, but is not involved in the actual court challenge.

"So we have companies not knowing whether their patents are valid. We have hospitals and governments not willing to take the risk, because it would cost a lot to defend one of these actions," he said, referring to potential law suits based on patent infringement.

"To take the risk, they may be violating the patents."

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CHEO launches lawsuit against owners of gene patent

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Newswise In a study led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Julian Martinez-Agosto, UCLA scientists have shown that two genes not previously known to be involved with the immune system play a crucial role in how progenitor stem cells are activated to fight infection. This discovery lays the groundwork for a better understanding of the role progenitor cells can play in immune system response and could lead to the development of more effective therapies for a wide range of diseases.

The two-year study was published online October 30, 2014 ahead of print in the journal Current Biology.

Progenitor cells are the link between stem cells and fully differentiated cells of the blood system, tissues and organs. This maturation process, known as differentiation, is determined in part by the original environment that the progenitor cell came from, called the niche. Many of these progenitors are maintained in a quiescent state or "standby mode" and are ready to differentiate in response to immune challenges (such as stress, infection or disease).

Dr. Gabriel Ferguson, a postdoctoral fellow in the lab of Dr. Martinez-Agosto and first author of the study, built upon the lab's previous research that utilized the blood system of the fruit fly species Drosophila, showing that a specific set of signals must be received by progenitor cells to activate their differentiation into cells that can work to fight infection after injury. Dr. Ferguson focused on two genes previously identified in stem cells but not in the blood system, named Yorkie and Scalloped, and discovered that they are required in a newly characterized cell type called a lineage specifying cell. These cells then essentially work as a switch, sending the required signal to progenitor cells.

The researchers further discovered that when the progenitor cells did not receive the required signal, the fly would not make the mature cells required to fight infection. This indicates that the ability of the blood system to fight outside infection and other pathogens is directly related to the signals sent by this new cell type.

"The beauty of this study is that we now have a system in which we can investigate how a signaling cell uses these two genes Yorkie and Scalloped, which have never before been shown in blood, to direct specific cells to be made," said Dr. Martinez-Agosto, associate professor of human genetics. "It can help us to eventually answer the question of how our body knows how to make specific cell types that can fight infection."

Drs. Martinez-Agosto and Ferguson and colleagues next hope that future studies will examine these genes beyond Drosophila and extend to mammalian models, and that the system will be used by the research community to study the role of the genes Yorkie and Scalloped in different niche environments.

"At a biochemical level, there is a lot of commonality between the molecular machinery in Drosophila and that in mice and humans," said Dr. Ferguson. "This study can further our shared understanding of how the microenvironment can regulate the differentiation and fate of a progenitor or stem cell."

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UCLA Gene Discovery Shows How Stem Cells Can Be Activated to Help Immune System Respond to Infection

By Danielle Ryan, Special to CNN

October 30, 2014 -- Updated 1846 GMT (0246 HKT)

Genetic research has been used to treat all kinds of disorders and diseases.

STORY HIGHLIGHTS

(CNN) -- Researchers have found dozens of new genes that may play a role in causing autism, according to two studies published Wednesday in the medical journal Nature.

Scientists identified 60 genes with a greater than 90% chance of increasing a child's autism risk. Previous research has yielded only 11 genes that had been confirmed with this level of certainty.

Though other studies have shown the importance of genetics in the development of autism, experts say these new studies zero in on the exact nature of the genetic mutations that cause the disorder.

The researchers say these genes appear to be clustering around three sets of key biological functions.

The first set focuses on the development of synapses in the brain, which are responsible for all kinds of communication between nerves. The second set is responsible for the creation of genetic instructions, and the third is responsible for DNA packaging within cells.

Each of these functions could have an effect on the individual that would cause the traits commonly associated with autism, according to one of the studies.

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Gene advance for spotting autism

PUBLIC RELEASE DATE:

29-Oct-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center @sumedicine

The ability to pop a working copy of a faulty gene into a patient's genome is a tantalizing goal for many clinicians treating genetic diseases. Now, researchers at the Stanford University School of Medicine have devised a new way to carry out this genetic sleight of hand.

The approach differs from that of other hailed techniques because it doesn't require the co-delivery of an enzyme called an endonuclease to clip the recipient's DNA at specific locations. It also doesn't rely on the co-insertion of genetic "on" switches called promoters to activate the new gene's expression.

These differences may make the new approach both safer and longer-lasting. Using the technique, the Stanford researchers were able to cure mice with hemophilia by inserting a gene for a clotting factor missing in the animals.

"It appears that we may be able to achieve lifelong expression of the inserted gene, which is particularly important when treating genetic diseases like hemophilia and severe combined immunodeficiency," said Mark Kay, MD, PhD, professor of pediatrics and of genetics. "We're able to do this without using promoters or nucleases, which significantly reduces the chances of cancers that can result if the new gene inserts itself at random places in the genome."

Using the technique, Kay and his colleagues were able to insert a working copy of a missing blood-clotting factor into the DNA of mice with hemophilia. Although the insertion was accomplished in only about 1 percent of liver cells, those cells made enough of the missing clotting factor to ameliorate the disorder.

Kay is the senior author of the research, which will be published Oct. 29 in Nature. The lead author is postdoctoral scholar Adi Barzel, PhD.

A possible alternative to CRISPR

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New way of genome editing cures hemophilia in mice; may be safer than older method

One kind of stem cell, those referred to as 'facultative', form part -- together with other cells -- of tissues and organs. There is apparently nothing that differentiates these cells from the others. However, they have a very special characteristic, namely they retain the capacity to become stem cells again. This phenomenon is something that happens in the liver, an organ that hosts cells that stimulate tissue growth, thus allowing the regeneration of the organ in the case of a transplant. Knowledge of the underlying mechanism that allows these cells to retain this capacity is a key issue in regenerative medicine.

Headed by Jordi Casanova, research professor at the Instituto de Biologa Molecular de Barcelona (IBMB) of the CSIC and at IRB Barcelona, and by Xavier Franch-Marro, CSIC tenured scientist at the Instituto de Biologa Evolutiva (CSIC-UPF), a study published in the journal Cell Reports reveals a mechanism that could explain this capacity. Working with larval tracheal cells of Drosophila melanogaster, these authors report that the key feature of these cells is that they have not entered the endocycle, a modified cell cycle through which a cell reproduces its genome several times without dividing.

"The function of endocycle in living organisms is not fully understood," comments Xavier Franch-Marro. "One of the theories is that endoreplication contributes to enlarge the cell and confers the production of high amounts of protein." This is the case of almost all larval cells of Drosophila.

The scientists have observed that the cells that enter the endocycle lose the capacity to reactivate as stem cells. "The endocycle is linked to an irreversible change of gene expression in the cell," explains Jordi Casanova, "We have seen that inhibition of endocycle entry confers the cells the capacity to reactivate as stem cells."

Cell entry into the endocycle is associated with the expression of the Fzr gene. The researchers have found that inhibition of this gene prevents this entry, which in turn leads to the conversion of the cell into an adult progenitor that retains the capacity to reactivate as a stem cell. Therefore, this gene acts as a switch that determines whether a cell will enter mitosis (the normal division of a cell) or the endocycle, the latter triggering a totally different genetic program with a distinct outcome regarding the capacity of a cell to reactivate as a stem cell.

Story Source:

The above story is based on materials provided by Institute for Research in Biomedicine (IRB Barcelona). Note: Materials may be edited for content and length.

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Mechanism that allows differentiated cell to reactivate as a stem cell revealed

For his contribution to the understanding of gene regulation and its potential ability to change agriculture and the treatment of disease and mental health, Professor Ryan Lister has been awarded the 2014 Frank Fenner Prize for Life Scientist of the Year.

Genes are not enough to explain the difference between a skin cell and a stem cell, a leaf cell and a root cell, or the complexity of the human brain. Genes dont explain the subtle ways in which your parents environment before you were conceived might affect your offspring.

Another layer of complexitythe epigenomeis at work determining when and where genes are turned on and off.

Ryan Lister is unravelling this complexity. Hes created ways of mapping the millions of molecular markers of where genes have been switched on or off, has made the first maps of these markers in plants and humans, and revealed key differences between the markers in cells with different fates.

Hes created maps of the epigenome in plants, which could enable plant breeders to modify crops to increase yields without changing the underlying DNA.

Hes explained a challenge for stem cell medicineshowing how, when we persuade, for example, skin cells to turn into stem cells, these cells retain a memory of their past. Their epigenome is different to that of natural embryonic stem cells. He believes this molecular memory could be reversed.

He has also recently explored the most complex system we knowthe human braindiscovering that its epigenome is extensively reconfigured in childhood during critical stages when the neural circuits are forming and maturing. These epigenome patterns may even underpin learning and memory. All of this in just 15 years since the beginning of his PhD.

For his contribution to the understanding of gene regulation and its potential ability to change agriculture and the treatment of disease and mental health, Professor Ryan Lister of the Australian Research Council Centre of Excellence in Plant Energy Biology at the University of Western Australia has been awarded the 2014 Frank Fenner Prize for Life Scientist of the Year.

The human body is composed of hundreds of different types of cells. Yet all are formed from the same set of instructions, the human genome. How does this happen?

On top of the genetic code sits another code, the epigenome. It can direct which genes are switched on and which are switched off, Ryan Lister says. The genome contains a huge volume of information, a parts list to build an entire organism. But controlling when and where the different components are used is crucial. The epigenetic code regulates the release of the genomes potential. Cells end up with different forms and functions through using different parts of the genome.

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Regulating genes to treat illness, grow food, and understand the brain