GM athletes could get their own events Scientists say they could be treated 'like racing cars' Power running, swimming and climbing could be first disciplines

PUBLISHED: 13:01 EST, 19 July 2012 | UPDATED: 13:01 EST, 19 July 2012

Superhuman athletes created by gene therapy and biomechanical engineering will one day be competing at the Olympics - but will need their own events, predict scientists.

Performance-enhancing technologies will advance to a point where they will not only extend human limits - but demand a events all of their own, similar to the Formula One version of car racing.

Professor Hugh Herr of the prestigious Massachusetts Institute of Technology said: 'For each one there will be a new sport - power running and power swimming and power climbing.

'Just like the invention of the bicycle led to the sport of cycling. What well see is the emergence of all kinds of new sports.'

Mechanical prosthetics will become much more proficient than the cheetah-style legs used by amputees including Oscar Pistorius from South Africa.

The first superhuman athlete? Oscar Pistorius trains at the track in South Africa.

The Paralympic gold medallist has now been approved to run in the London 2012 Olympics even though his prosthetics lack the stiffness of a human ankle and cant generate the same forces.

Prof Herrs lab at the Massachusetts Institute of Technology is currently working on a bionic running leg.

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Forget the Olympics - Here come the Superhuman games for genetically enhanced humans

Washington, July 9 (ANI): A new gene therapy approach capable of delivering full-length versions of large genes and improving skeletal muscle function may hold new hope for treating dysferlinopathies and other muscular dystrophies, scientists say.

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New gene transfer strategy shows promise to treat muscular dystrophies

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/kxltqj/gene_therapy_marke) has announced the addition of the "Gene Therapy Market to 2018 - Product Development Slowed by Clinical Failures, Close Regulatory Surveillance and High Compliance Standards" report to their offering.

Gene Therapy: the Next Big Step in Cancer Treatments.

The fight against cancer is leading a new movement in gene therapy, as the failure of conventional cancer therapies is fuelling demand for new treatments, according to a new report by healthcare experts GBI Research.

The new report* states that gene therapy technology is still in its nascent stage, and high levels of regulatory surveillance in clinical development is affecting progress. However, the increasing potential of upcoming treatments and shortcomings in traditional therapies is gradually leading to broader acceptance of gene therapy in medicine.

Therapies such as chemotherapy and hormone therapy control the progression of diseases, but are often associated with severe side effects, such as nausea, hair loss and abnormal blood cell counts. Once administered, the drugs induce systemic action throughout the body, and patients often die due to the side effects of treatment rather than the cancer itself. The inability of these conventional therapies to cure diseases has created a significant unmet need in the treatment of cancer, as well as Human Immunodeficiency Virus (HIV), autoimmune diseases, and viral infections.

Targeted therapies such as monoclonal antibodies, stem cell therapies, Ribonucliec Acid (RNA) therapies and gene therapies have initially shown better efficacy and safety profiles compared to chemotherapies.

Gene therapy has several promising drug candidates, which are likely to drive the growth of the gene therapy market if clinical trials are successful. Collategene by AnGes MG, Cardium Therapeutics' Generx, and Vical Incorporation's Allovectin-7 are in development for a wide range of cancer indications, and are expected to compete in the oncology therapeutics market as the market acceptance of gene therapy improves over time.

Companies Mentioned

- ReGenX Biosciences

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Research and Markets: Gene Therapy Market to 2018 - Product Development Slowed by Clinical Failures, Close Regulatory ...

Public release date: 9-Jul-2012 [ | E-mail | Share ]

Contact: Erin Pope Erin.Pope@NationwideChildrens.org 614-355-0495 Nationwide Children's Hospital

The challenge of treating patients with genetic disorders in which a single mutated gene is simply too large to be replaced using traditional gene therapy techniques may soon be a thing of the past. A Nationwide Children's Hospital study describes a new gene therapy approach capable of delivering full-length versions of large genes and improving skeletal muscle function. The strategy may hold new hope for treating dysferlinopathies and other muscular dystrophies.

A group of untreatable muscle disorders known as dysferlinopathies are caused by mutations in the dysferlin gene. Patients with these disorders, including limb girdle muscular dystrophy type 2B, are typically diagnosed in their early twenties. Approximately one-third will become wheelchair dependent by their mid-30s.

Gene therapy using adeno-associated virus (AAV) to deliver genes to cells has been pursued as an option for some patients with muscular dystrophy. However, AAV's packaging limitations have served as obstacles in using gene therapy to deliver large genes like dysferlin. Scientists in the past have attempted to work around AAV's packaging limitations by inserting a small version of large genes into the viral vector to induce gene expression. Some have also used more than one viral vector at a time to deliver a large gene. However, micro and mini versions of large genes don't always have the power of full-length gene expression and an increased viral load can lead to negative side effects.

"We have had success in the clinic using AAV gene therapy with limb girdle muscular dystrophy type 2D, which is caused by mutations in the alpha-sarcoglycan gene," said Louise Rodino-Klapac, PhD, principal investigator in the Center for Gene Therapy at The Research Institute of Nationwide Children's Hospital. "However, the dysferlin gene is very large, about six times larger than the alpha-sarcoglycan gene and can't fit into a traditional AAV vector."

A 2008 study identified AAV5, an AAV serotype that could package large transcripts. "This made us wonder whether it could be used for gene replacement requiring inserts as large as the dysferlin gene," said Dr. Rodino-Klapac.

In their 2012 study appearing in PLoS ONE, Dr. Rodino-Klapac's team used AAV5 to package a full-length, intact dysferlin gene and directly deliver it to the diaphragm of dysferlin-deficient mice. They also injected the leg muscles of dysferlin-deficient mice using both intramuscular and vascular approaches to further evaluate whether the gene delivery could improve skeletal muscle function.

They found that both the intravascular and intramuscular delivery approaches led to full-length, intact dysferlin gene expression in the leg and diaphragm muscle cells of the mice. More importantly, they saw that the newly-restored dysferlin repaired membrane deficits previously seen in the dysferlin-deficient mice.

"Our findings demonstrate highly favorable results with full restoration of dysferlin without compromise in function," said Dr. Rodino-Klapac. "With regard to neuromuscular diseases, these studies provide new perspective for conditions caused by mutations of large genes. Duchenne muscular dystrophy is the most common severe childhood muscular dystrophy and would seem to benefit from expression of the larger transcripts than mini- and micro-dystrophins that only partially restore physiologic function in mouse models of the disease."

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New gene transfer strategy shows promise for limb girdle and other muscular dystrophies

Washington, July 8 (ANI): Researchers have established a novel gene therapy strategy which is an excellent substitute for the current expensive and uncontrollable Vascular endothelial growth factor (VEGF) gene delivery system.

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New economical gene therapy strategy promotes cardiac repair

ScienceDaily (July 6, 2012) Dr Changfa Guo, Professor Chunsheng Wang and their co-investigators from Zhongshan hospital Fudan University, Shanghai, China have established a novel hyperbranched poly(amidoamine) (hPAMAM) nanoparticle based hypoxia regulated vascular endothelial growth factor (HRE-VEGF) gene therapy strategy which is an excellent substitute for the current expensive and uncontrollable VEGF gene delivery system.

This discovery, reported in the June 2012 issue of Experimental Biology and Medicine, provides an economical, feasible and biocompatible gene therapy strategy for cardiac repair.

Transplantation of VEGF gene manipulated mesenchymal stem cells (MSCs) has been proposed as a promising therapeutic method for cardiac repair after myocardium infarction. However, the gene delivery system, including the VEGF gene and delivery vehicle, needs to be optimized. On one hand, long-term and uncontrollable VEGF over-expression in vivo has been observed to lead to hemangioma formation instead of functional vessels in animal models. On the other hand, though non-viral gene vector can circumvent the limitations of virus, drawbacks of the current non-viral vectors, such as complex synthesis procedure, limited transfection efficiency and high cytotoxicity, still needs to be overcome.

Co-investigators, Drs. Kai Zhu and Hao Lai, said "Hypoxia response elements were inserted into the promoter region of VEGF gene to form HRE-VEGF, which provided a safer alternative to the conventionally available VEGF gene." "The HRE-VEGF up-regulates gene expression under hypoxic conditions caused by ischemic myocardium and turns it off under normoxia condition when the regional oxygen supply is adequate."

The hPAMAM nanoparticles, which exhibit high gene transfection efficiency and low cytotoxicity during the gene delivery process, can be synthesized by a simpler and more economical one-step/pot polymerization technique. Drs. Zhu and Lai, said "Using the hPAMAM based gene delivery approach, our published and unpublished results explicitly demonstrated that it was an economical, effective and biocompatible gene delivery vehicle."

Dr Guo concluded that "Treatment with hPAMAM-HRE-VEGF transfected MSCs after myocardium infarction improved the myocardial VEGF level, which improved graft MSC survival, increased neovascularization and ultimately improved heart function. And this novel VEGF gene delivery system may have clinical relevance for tissue repair in other ischemic diseases."

Dr. Steve Goodman, Editor-in-Chief of Experimental Biology and Medicine said "Guo and colleagues have provided an exciting new nanoparticle based gene therapy for cardiac repair. This novel approach has great promise for repair of the heart after myocardial infarction."

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An economical, effective and biocompatible gene therapy strategy promotes cardiac repair

ScienceDaily (July 2, 2012) Getting under your skin takes on a brave new meaning thanks to Northwestern University research that could transform gene regulation.

A team led by a physician-scientist and a chemist -- from the fields of dermatology and nanotechnology -- is the first to demonstrate the use of commercial moisturizers to deliver gene regulation technology that has great potential for life-saving therapies for skin cancers.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Applied directly to the skin, the drug penetrates all of the skins layers and can selectively target disease-causing genes while sparing normal genes. Once in cells, the drug simply flips the switch of the troublesome genes to off.

A detailed study of a method that could dramatically redefine the field of gene regulation will be published online during the week of July 2 by the Proceedings of the National Academy of Sciences (PNAS).

Early targets of the novel treatment are melanoma and squamous cell carcinoma (two of the most common types of skin cancer), the common inflammatory skin disorder psoriasis, diabetic wound healing and a rare genetic skin disorder that has no effective treatment (epidermolytic ichthyosis). Other targets could even include wrinkles that come with aging skin.

The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier, said co-senior author Amy S. Paller, M.D., the Walter J. Hamlin Professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwesterns Skin Disease Research Center.

This allows us to treat a skin problem precisely where it is manifesting -- on the skin, she said. We can target our therapy to the drivers of disease, at a level so minute that it can distinguish mutant genes from normal genes. Risks are minimized, and side effects have not been seen to date in our human skin and mouse models.

A co-senior author of the paper, Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwesterns International Institute for Nanotechnology.

Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the FDA-cleared technology now is the basis of powerful commercialized medical diagnostic tools. This, however, is the first realization that the nanostructures naturally enter skin and that they can deliver a large payload of therapeutics.

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Breaking the skin barrier: Drugs topically deliver gene therapy via commercial moisturizers for skin disease treatment

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

Contact: Mika OnoScripps Research Institute scientists develop alternative to gene therapy mikaono@scripps.edu 858-784-2052 Scripps Research Institute

LA JOLLA, CA July 1, 2012 Scientists at The Scripps Research Institute have discovered a surprisingly simple and safe method to disrupt specific genes within cells. The scientists highlighted the medical potential of the new technique by demonstrating its use as a safer alternative to an experimental gene therapy against HIV infection.

"We showed that we can modify the genomes of cells without the troubles that have long been linked to traditional gene therapy techniques," said the study's senior author Carlos F. Barbas III, who is the Janet and Keith Kellogg II Professor of Molecular Biology and Chemistry at The Scripps Research Institute.

The new technique, reported in Nature Methods on July 1, 2012, employs zinc finger nuclease (ZFN) proteins, which can bind and cut DNA at precisely defined locations in the genome. ZFNs are coming into widespread use in scientific experiments and potential disease treatments, but typically are delivered into cells using potentially risky gene therapy methods.

The Scripps Research scientists simply added ZFN proteins directly to cells in a lab dish and found that the proteins crossed into the cells and performed their gene-cutting functions with high efficiency and minimal collateral damage.

"This work removes a major bottleneck in the efficient use of ZFN proteins as a gene therapy tool in humans," said Michael K. Reddy, who oversees transcription mechanism grants at the National Institutes of Health's (NIH) National Institute of General Medical Sciences, which helped fund the work, along with an NIH Director's Pioneer Award. "The directness of Dr. Barbas's approach of 'simply' testing the notion that ZFNs could possess an intrinsic cell-penetrating ability is a testament to his highly creative nature and further validates his selection as a 2010 recipient of an NIH Director's Pioneer Award."

Questioning Assumptions

ZFNs, invented in the mid-1990s, are artificial constructs made of two types of protein: a "zinc-finger" structure that can be designed to bind to a specific short DNA sequence, and a nuclease enzyme that will cut DNA at that binding site in a way that cells can't repair easily. The original technology to make designer zinc finger proteins that are used to direct nucleases to their target genes was first invented by Barbas in the early 1990s.

Scientists had assumed that ZFN proteins cannot cross cell membranes, so the standard ZFN delivery method has been a gene-therapy technique employing a relatively harmless virus to carry a designer ZFN gene into cells. Once inside, the ZFN gene starts producing ZFN proteins, which seek and destroy their target gene within the cellular DNA.

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Scripps Research Institute Scientists Develop Alternative to Gene Therapy

London, July 2 : Scientists at The Scripps Research Institute have found a surprisingly simple and safe method to disrupt specific genes within cells.

They highlighted the medical potential of the new technique by demonstrating its use as a safer alternative to an experimental gene therapy against HIV infection.

"We showed that we can modify the genomes of cells without the troubles that have long been linked to traditional gene therapy techniques," said the study's senior author Carlos F. Barbas III, who is the Janet and Keith Kellogg II Professor of Molecular Biology and Chemistry at The Scripps Research Institute.

The new technique employs zinc finger nuclease (ZFN) proteins, which can bind and cut DNA at precisely defined locations in the genome. ZFNs are coming into widespread use in scientific experiments and potential disease treatments, but typically are delivered into cells using potentially risky gene therapy methods.

The Scripps Research scientists simply added ZFN proteins directly to cells in a lab dish and found that the proteins crossed into the cells and performed their gene-cutting functions with high efficiency and minimal collateral damage.

ZFNs, invented in the mid-1990s, are artificial constructs made of two types of protein: a "zinc-finger" structure that can be designed to bind to a specific short DNA sequence, and a nuclease enzyme that will cut DNA at that binding site in a way that cells can't repair easily. The original technology to make designer zinc finger proteins that are used to direct nucleases to their target genes was first invented by Barbas in the early 1990s.

Scientists had assumed that ZFN proteins cannot cross cell membranes, so the standard ZFN delivery method has been a gene-therapy technique employing a relatively harmless virus to carry a designer ZFN gene into cells. Once inside, the ZFN gene starts producing ZFN proteins, which seek and destroy their target gene within the cellular DNA.

One risk of the gene-therapy approach is that viral DNAeven if the virus is not a retrovirusmay end up being incorporated randomly into cellular DNA, disrupting a valuable gene such as a tumor-suppressor gene. Another risk with this delivery method is that ZFN genes will end up producing too many ZFN proteins, resulting in a high number of "off-target" DNA cuts.

In the new study, Barbas and his colleagues set out to find a safer ZFN delivery method that didn't involve the introduction of viruses or other genetic material into cells. They experimented initially with ZFN proteins that carry extra protein segments to help them penetrate cell membranes, but found these modified ZFNs hard to produce in useful quantities. Eventually, the scientists recognized that the zinc-finger segments of ordinary ZFNs have properties that might enable the proteins to get through cell membranes on their own.

Next, the team showed how the new technique could be used in a ZFN-based strategy against HIV infection.

Read the original:

New technique offers safer alternative to gene therapy for HIV treatment

ScienceDaily (July 1, 2012) Scientists at The Scripps Research Institute have discovered a surprisingly simple and safe method to disrupt specific genes within cells. The scientists highlighted the medical potential of the new technique by demonstrating its use as a safer alternative to an experimental gene therapy against HIV infection.

"We showed that we can modify the genomes of cells without the troubles that have long been linked to traditional gene therapy techniques," said the study's senior author Carlos F. Barbas III, who is the Janet and Keith Kellogg II Professor of Molecular Biology and Chemistry at The Scripps Research Institute.

The new technique, reported in Nature Methods on July 1, 2012, employs zinc finger nuclease (ZFN) proteins, which can bind and cut DNA at precisely defined locations in the genome. ZFNs are coming into widespread use in scientific experiments and potential disease treatments, but typically are delivered into cells using potentially risky gene therapy methods.

The Scripps Research scientists simply added ZFN proteins directly to cells in a lab dish and found that the proteins crossed into the cells and performed their gene-cutting functions with high efficiency and minimal collateral damage.

"This work removes a major bottleneck in the efficient use of ZFN proteins as a gene therapy tool in humans," said Michael K. Reddy, who oversees transcription mechanism grants at the National Institutes of Health's (NIH) National Institute of General Medical Sciences, which helped fund the work, along with an NIH Director's Pioneer Award.

Questioning Assumptions

ZFNs, invented in the mid-1990s, are artificial constructs made of two types of protein: a "zinc-finger" structure that can be designed to bind to a specific short DNA sequence, and a nuclease enzyme that will cut DNA at that binding site in a way that cells can't repair easily. The original technology to make designer zinc finger proteins that are used to direct nucleases to their target genes was first invented by Barbas in the early 1990s.

Scientists had assumed that ZFN proteins cannot cross cell membranes, so the standard ZFN delivery method has been a gene-therapy technique employing a relatively harmless virus to carry a designer ZFN gene into cells. Once inside, the ZFN gene starts producing ZFN proteins, which seek and destroy their target gene within the cellular DNA.

One risk of the gene-therapy approach is that viral DNA -- even if the virus is not a retrovirus -- may end up being incorporated randomly into cellular DNA, disrupting a valuable gene such as a tumor-suppressor gene. Another risk with this delivery method is that ZFN genes will end up producing too many ZFN proteins, resulting in a high number of "off-target" DNA cuts. "The viral delivery approach involves a lot of off-target damage," said Barbas.

In the new study, Barbas and his colleagues set out to find a safer ZFN delivery method that didn't involve the introduction of viruses or other genetic material into cells. They experimented initially with ZFN proteins that carry extra protein segments to help them penetrate cell membranes, but found these modified ZFNs hard to produce in useful quantities. Eventually, the scientists recognized that the zinc-finger segments of ordinary ZFNs have properties that might enable the proteins to get through cell membranes on their own.

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Scientists develop alternative to gene therapy

NEW YORK, July 2, 2012 /PRNewswire/ --Reportlinker.com announces that a new market research report is available in its catalogue:

http://www.reportlinker.com/p0922674/Gene-Therapy-Market-to-2018---Product-Development-Slowed-by-Clinical-Failures-Close-Regulatory-Surveillance-and-High-Compliance-Standards.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Biological_Therapy

Gene Therapy Market to 2018 - Product Development Slowed by Clinical Failures, Close Regulatory Surveillance and High Compliance Standards

This report is built using data and information sourced from proprietary databases, primary and secondary research, and in-house analysis by GBI Research's team of industry experts.

Gene therapies are biological compounds, which modify or replace disease-causing genes. These therapies are the new therapeutic class aimed at treating diseases associated with genetic mutations. Gene therapy promises to provide new treatments for a large number of inherited and acquired diseases. The basic concept of gene therapy is to introduce a piece of genetic material into target cells, which will result in either a cure for the disease or a slowdown in the progression of the disease. It involves the transfer of a functional gene copy into specific cells of an individual in order to repair a faulty gene copy. It may be used to replace a defective gene, or to introduce a new gene to cure a condition.

For example, mutations in genes on the X chromosome lead to X chromosome-linked genetic diseases such as Duchenne muscular dystrophy and hemophilia. Since males have only one copy of the genes from this chromosome, there is no other normal copy available to fulfill a defective gene's function which is present on the X chromosome. If the normal copy of the mutated gene is delivered in the nucleus externally through a delivery agent, the cells can produce the normal gene products and the disease would be treated.

From a commercial perspective, there is a huge unmet need in oncology and autoimmune diseases, amongst others, that could further drive growth of the pharmaceutical and biotech industry. The unmet need is largely driven by the lack of efficacious and safe therapeutic products based on conventional pharmaceutical and biotech research. Gene therapy is a new therapeutic category that has the potential to satisfy this unmet need, especially considering how efficacious and safe this therapeutic category is expected to be.

GBI Research's analysis suggests that therapies developed using gene therapy technology can address the majority of the unmet needs prevailing in the current pharmaceutical market. The inherent structure of gene therapies and their potential to replace the functions of defective genes make them highly effective to knockdown any gene that was previously unapproachable by conventional therapies. Gene therapies are poised to become the next most promising class of drugs in the pharmaceutical industry. Currently there are only three approved products, namely Gendicine, Oncorine and Rexin-G, with a collective market little above $2.8m. Since first movers always have the competitive edge, many large pharmaceutical and biotechnology companies have already commenced their R&D activities on gene therapies.

This report provides insights into the major unmet needs prevailing in the current pharmaceutical industry, and points to gene therapies as the solution to these unmet needs. The report also elucidates the promising late-stage gene therapy pipeline, and provides insights into the gene therapeutics R&D pipeline and funding opportunities.

- Analysis of the leading therapeutic segments for which clinical development in gene therapy is being conducted.

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Gene Therapy Market to 2018 - Product Development Slowed by Clinical Failures, Close Regulatory Surveillance and High ...

By Jon Bardin, Los Angeles Times / For the Booster Shots blog 7:01 p.m. EST, June 29, 2012

A new vaccine may help prevent the brain stimulation that keeps smokers from being able to quit. (Francine Orr / Los Angeles Times / Jun 29, 2012)

Cant kick cigarettes? A vaccine may one day help by preventing nicotine from reaching its target in the brain, according to research published this week.

Most smoking therapies do a poor job of stopping the habit 70% to 80% of smokers who use an approved drug therapy to quit relapse. Scientists say this is because the targets of existing therapies are imperfect, only slightly weakening nicotines ability to find its target in the brain.

So some scientists have been trying a different approach creation of a vaccine. It would work like this: People would inject the vaccine like a shot, and the vaccine would create nicotine antibodies, molecules that can snatch up nicotine from the bloodstream before it reaches the brain. The vaccine could be used by smokers who want to quit or people who are worried about getting addicted to cigarettes in the future.

Researchers have tried to create vaccines in the past, but the ones theyve come up with have not been particularly effective. The authors of the new study say this may be because previous vaccines just didnt create enough antibodies to get rid of all the nicotine.

The new report, published in the journal Science Translational Medicine, attempts to solve this problem via gene therapy, in which a new gene is inserted into the body to do a particular job.

First the scientists at Weill Cornell Medical College in New York City put a gene that produces a nicotine antibody into mice. The gene was taken into the mices livers, and the liver started producing the antibody. Once produced, the antibody connected with nicotine, trapping it and preventing it from making its way to the brain, where it would otherwise have caused the pleasurable, addictive effects it is so known for.

Because of this trick, the researchers say that the new vaccine should only have to be injected once, and it will work for life, continuing to produce new antibodies in the liver.

The vaccine was effective: When mice were given nicotine intravenously, ones with the vaccine had a 47-fold drop in levels of nicotine in the blood compared with ones that hadnt received the vaccine. The antibody had successfully captured the nicotine in the bloodstream before it could reach the brain.

Originally posted here:

Gene therapy for smoking kills pleasure of nicotine

Cant kick cigarettes? A vaccine may one day help by preventing nicotine from reaching its target in the brain, according to research published this week.

Most smoking therapies do a poor job of stopping the habit 70% to 80% of smokers who use an approved drug therapy to quit relapse. Scientists say this is because the targets of existing therapies are imperfect, only slightly weakening nicotines ability to find its target in the brain.

So some scientists have been trying a different approach creation of a vaccine. It would work like this: People would inject the vaccine like a shot, and the vaccine would create nicotine antibodies, molecules that can snatch up nicotine from the bloodstream before it reaches the brain. The vaccine could be used by smokers who want to quit or people who are worried about getting addicted to cigarettes in the future.

Researchers have tried to create vaccines in the past, but the ones theyve come up with have not been particularly effective. The authors of the new study say this may be because previous vaccines just didnt create enough antibodies to get rid of all the nicotine.

The new report, published in the journal Science Translational Medicine, attempts to solve this problem via gene therapy, in which a new gene is inserted into the body to do a particular job.

First the scientists at Weill Cornell Medical College in New York City put a gene that produces a nicotine antibody into mice. The gene was taken into the mices livers, and the liver started producing the antibody. Once produced, the antibody connected with nicotine, trapping it and preventing it from making its way to the brain, where it would otherwise have caused the pleasurable, addictive effects it is so known for.

Because of this trick, the researchers say that the new vaccine should only have to be injected once, and it will work for life, continuing to produce new antibodies in the liver.

The vaccine was effective: When mice were given nicotine intravenously, ones with the vaccine had a 47-fold drop in levels of nicotine in the blood compared with ones that hadnt received the vaccine. The antibody had successfully captured the nicotine in the bloodstream before it could reach the brain.

The work is still preliminary, and the authors admit the technology is far from ready for human use; it has only been used in rodents so far. But given the results, and the continued public health effect of smoking, it may not be too long before all those boxes of Nicorette are replaced with a single trip to the doctors office.

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New gene therapy for smoking kills the pleasure of nicotine

Featured Article Academic Journal Main Category: Smoking / Quit Smoking Also Included In: Immune System / Vaccines Article Date: 28 Jun 2012 - 2:00 PDT

Current ratings for: New Smoking Vaccine Using Gene Therapy Being Developed

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In a study reported in the journal Science Translational Medicine this week, Researchers at Weill Cornell Medical College in New York City show how a single dose of the vaccine protected mice, over their lifetime, against nicotine addiction.

The addictive properties of the nicotine in tobacco smoke is a huge barrier to success with current smoking cessation approaches, say the authors in their paper.

Previous work using gene therapy vaccination in mice to treat certain eye disorders and tumors, gave them the idea a similar approach might work against nicotine.

The new anti-nicotine vaccine is based on an adeno-associated virus (AAV) engineered to be harmless. The virus carries two pieces of genetic information: one that causes anti-nicotine monoclonal antibodies to be created, and the other that targets its insertion into the nucleus of specific cells in the liver, the hepatocytes.

The result is the animal's liver becomes a factory continuously producing antibodies that gobble up the nicotine as soon as it enters the bloodstream, denying it the opportunity to enter the brain.

The researchers write:

"In mice treated with this vector, blood concentrations of the anti-nicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine."

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New Smoking Vaccine Using Gene Therapy Being Developed

Forget patches: gene therapy could suppress cigarette cravings by preventing the brain from receiving nicotine. The treatment is effective in mice, but with gene therapy still not fully tested in people, human trials and treatments are a long way off.

For drug users who really can't quit, vaccination might one day be an option, and several groups have attempted to develop such treatments.

But nicotine vaccines have mostly flopped. This is because nicotine is a very small molecule, so the immune system has difficulty recognising the drug and making antibodies that bind it. Physicians can inject antibodies directly into a patient, but this treatment quickly becomes expensive because the antibodies don't last long.

Ronald Crystal of Weill Cornell Medical College in New York and his team decided to bypass that problem by putting the gene for a nicotine antibody right into the body.

They selected the strongest antibody against nicotine from a mouse and isolated the gene that produced it. They then placed this gene into a carrier called adeno-associated virus (AAV), which is widely used for gene therapy.

When the researchers injected the virus and its cargo into nicotine-addicted mice, the rodents' livers took up the virus, began making antibodies and pumped them into the bloodstream. The researchers injected two cigarettes' worth of nicotine into AAV-infected mice. The antibodies were able to bind 83 per cent of the drug before it reached the brain.

Without their drug, the mice's behaviour changed. Nicotine usually causes mice to "chill out", Crystal says, but the researchers found that the treated mice stayed active and their heart rates stayed normal when they received nicotine.

Eighteen weeks later, the mice's livers were still making the antibody, suggesting that the therapy might render nicotine useless to smokers for long periods.

Jude Samulski at the University of North Carolina at Chapel Hill, who was part of the team that developed AAV as a gene therapy vector, says he's "ecstatic" that the vector has come so far. He calls the research "a gorgeous piece of work" that has "leapfrogged" the difficulties faced by vaccines.

But he has doubts about whether gene therapy is well-tested enough to be used to treat nicotine addiction. So far, AAV has been clinically tested in people with HIV or terminal cancer where potential benefits far outweigh the risks. "It's ahead of its time. In 10 years there may be enough safety data," he says. "Quitting smoking might be easier."

Read more from the original source:

Gene therapy curbs nicotine addiction in mice

By Elizabeth Lopatto - 2012-06-27T18:00:00Z

An experimental vaccine againstnicotine, delivered using gene therapy, prevents the substance from reaching the brain and may make quitting easier for smokers, a study using mice indicates.

A single dose of vaccine allowed the liver to produce antibodies that stopped most of the nicotine from getting to the brain, according to a study in the journal Science Translational Medicine. The concentration of nicotine in the brains of treated mice was just 15 percent of that in untreated ones.

Of the more than 4,000 chemicals in cigarette smoke, it is nicotine that leads to addiction, the researchers wrote. Keeping the substance away from the brain might stymie nicotines addictive power by preventing smokers from enjoying their cigarettes, giving them no incentive to relapse, said Ronald Crystal, one of the studys researchers.

This looks really terrific if youre a mouse, but the caveat is that they arent small humans, said Crystal, the chairman of genetic medicine at Weill Cornell Medical College in New York, in a telephone interview.

The gene therapy delivers the vaccine to the liver using a virus engineered not to be harmful. The gene sequence for the antibodies is inserted into liver cells, which then begin to create antibodies to nicotine.

The antibody is floating around like Pac-Man in the blood, Crystal said. If you give the nicotine and the anti- nicotine gobbles it up, it doesnt reach the brain.

The idea of vaccines against nicotine has emerged before, in the form of injections used to trigger an immune response. Those methods proved ineffective, according to the researchers. They turned to gene therapy to trigger production of antibodies.

About 20 percent of U.S. adults are smokers, and most relapse shortly after quitting.

We dont have very effective therapies, Crystal said. The problem is even with the drugs we have now, 70 percent of people go back to smoking within 6 months of trying to quit.

Continue reading here:

Gene Therapy Against Nicotine May Someday Help Smokers Quit

ScienceDaily (June 26, 2012) In the brains of humans and non-human primates, over 100 billion nerve cells build up complicated neural circuits and produce higher brain functions. When an attempt is made to perform gene therapy for neurological diseases like Parkinson's disease, it is necessary to specify a responsible neural circuit out of many complicated circuits.Until now, however, it was difficult to introduce a target gene into this particular circuit selectively.

The collaborative research group consisting of Professor Masahiko Takada from Primate Research Institute, Kyoto University, Professor Atsushi Nambu from National Institute for Physiological Sciences, National Institutes of Natural Sciences, and Professor Kazuto KOBAYASHI from Fukushima Medical University School of Medicine have now developed a gene transfer technique that can "eliminate"a specific neural circuit in non-human primates for the first time.

They applied this technique to the basal ganglia, the brain region that is affected in movement disorders such as Parkinson's disease, and successfully eliminated a particular circuit selectively to elucidate its functional role. This technique can be applied to gene therapy for various neurological diseases in humans. This research achievement was supported by the Strategic Research Program of Brain Sciences by MEXT of Japan.

The research group developed a special viral vector, NeuRet-IL-2R alpha-GFP viral vector, expressing human interleukin type 2 alpha receptor, which the cell death inducer immunotoxin binds. Nerve cells transfected with this viral vector cause cell death by immunotoxin. First, the research group injected the viral vector into the subthalamic nucleus that is a component of the basal ganglia. Then, they injected immunotoxin into the motor cortex, an area of the cerebral cortex that controls movement, and succeed in selective elimination of the "hyperdirect pathway" that is one of the major circuits connecting the motor cortex to the basal ganglia. As a result, they have discovered that neuronal excitation observed at the early stage occurs through this hyperdirect pathway when motor information derived from the cortex enters the basal ganglia.

Professors Takada and Nambu expect that this gene transfer technique enables us to elucidate higher brain functions in primates and to develop primate models of various psychiatric/neurological disorders and their potential treatments including gene therapy. They think that this should provide novel advances in the field of neuroscience research that originate from Japan.

This research was supported by the Strategic Research Program of Brain Sciences by MEXT of Japan.

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The above story is reprinted from materials provided by National Institute for Physiological Sciences.

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Transgenic technique 'eliminates' a specific neural circuit in brain of primates

Public release date: 25-Jun-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, June 25, 2012Gene therapy to replace the protein missing in Pompe disease can be effective if the patient's immune system does not react against the therapy. Targeted delivery of the gene to the liver, instead of throughout the body,suppresses the immune response, improving the therapeutic effect, according to an article published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc. The article is available free online at the Human Gene Therapy website.

"The current unmet medical need in Pompe disease is for prevention of immune responses against standard-of-care enzyme replacement therapy," says coauthor Dwight Koeberl, MD, PhD. "However, we foresee a future application of the dual vector strategy described in this paper, including a liver-expressing vector along with a ubiquitously expressing vector, which might achieve much higher efficacy than either vector alone."

In the article "Immunodominant Liver-Specific Expression Suppresses Transgene-Directed Immune Responses in Murine Pompe Disease," Ping Zhang and coauthors from Duke University Medical Center (Durham, NC), targeted a gene delivery vector carrying the therapeutic gene to the livers of mice with Pompe disease. Not only did the liver-specific expression of the protein induce immune tolerance, but when combined with non-targeted delivery of the therapeutic gene it also boosted the overall effectiveness of the treatment.

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About the Journal

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies is an authoritative peer-reviewed journal published monthly in print and online that presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Tables of content and a free sample issue may be viewed online at the Human Gene Therapy website.

About the Publisher

Mary Ann Liebert, Inc. is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available at the Mary Ann Liebert, Inc. website.

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Targeted gene therapy enhances treatment for Pompe disease

By Elizabeth Lopatto - 2012-06-25T19:00:00Z

Chronic stress appears to block a gene that guards against brain atrophy associated with depression, according to a study in rats that may help guide new treatments for mood disorders.

The gene, called neuritin, appears to be responsible for keeping healthy neuron connections in certain parts of the brain, according to the study published in the Proceedings of the National Academy of Sciences. Rats whose genes were suppressed were more anxious and depressed than those whose genes werent, an experiment found. Further, activating the gene led to an antidepressant response.

The research adds evidence to the idea that depression may be caused by atrophy in the hippocampus, the part of the brain responsible for mood and memory. Scientists have previously shown that some antidepressants increase the growth of new connections, called synapses, between neurons.

This is based on findings that basically stress and depression have been shown to cause atrophy, said Ronald Duman, a study author and professor of psychiatry at Yale University in New Haven, Connecticut, in a telephone interview. Theres good evidence theres a loss of synaptic connections in depressed rodents and depressed patients. If you dont have the appropriate number of connections in synapses, your brain isnt going to function properly.

Researchers found that chronically stressed rats, those who had been deprived of food, forced to swim in cold water, exposed to frightening odors and other stressors, had lower levels of neuritin expression and exhibited depressed behavior. The researchers then dosed the stressed rats with neuritin-boosting therapy, which improved the animals ability to swim longer without giving up in a test.

In another experiment reported in the study, rats were dosed with gene therapy to boost neuritins availability in the brain. That led to new neuron growth. Researchers also used gene therapy to suppress neuritin. These animals were less likely to eat right away and were more likely to show despairing behaviors when they were subjected to stress.

An estimated 9 percent of American adults are depressed, according to the U.S. Centers for Disease Control and Prevention. Discovering new drugs to treat people who are depressed may decrease disability and suicide rates, according to background information in the paper.

Its not clear exactly how current antidepressants including selective serotonin reuptake inhibitors, or SSRIs, like Eli Lilly & Co. (LLY)s Prozac, work in the brain. SSRIs are designed to block the reabsorption of the brain chemical serotonin. Still, previous work attempting to show serotonin is solely responsible for depression has been unsuccessful. The alternative theory about the role of neurogenesis developed in response.

Todays study shows a causal link between neuritin and depression, at least in rats, Duman said. Human studies will be more complicated, in part because there isnt a known drug that acts directly on neuritin in humans.

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Stress Blocks Gene That Guards Brain Against Depression

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/skdhnn/translational_rege) has announced the addition of the "Translational Regenerative Medicine - Oncology, CNS and Cardiovascular-Rich Pipeline Features Innovative Stem Cell and Gene Therapy Applications" report to their offering.

More Guidelines Needed to Grow Regenerative Medicine Market, Report Finds

Standardized research guidelines are needed to control and encourage the development of gene therapy and stem cell treatments, according to a new report by healthcare experts GBI Research.

The new report* shows how regenerative medicine is seen as an area with high future potential, as countries need ways to cope with the burden of an aging population.

The stem cell market alone is predicted to grow to around $5.1 billion by 2014, while gene therapy has also shown promise despite poor understanding of some areas of regenerative medicine and a lack of major approvals (the only approvals to date being made in Asia).

Up until now, securing research within clinics has been difficult, with a high number of failures and discontinuations throughout all phases of clinical study. Stem cell therapy uses bone marrow transplants as an established treatment method, but the development of the therapy into further applications and has not yet become common practice.

Similarly, tissue engineering has been successful in the areas of skin and bone grafts, but translation into more complex therapies has been an issue for researchers. Although scientific possibilities are ever-increasing, the true potential of regenerative medicine has yet to be demonstrated fully.

A desire to discover new and innovative technologies has encouraged governments in the UK and Singapore to focus directly on regenerative medicine as a future potential economy booster.

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Research and Markets: Translational Regenerative Medicine - Oncology, CNS and Cardiovascular-Rich Pipeline Features ...