ScienceDaily (Oct. 24, 2012) Oregon Health & Science University's development of a new gene therapy method to prevent certain inherited diseases has reached a significant milestone. Researchers at the university's Oregon National Primate Research Center and the OHSU Department of Obstetrics & Gynecology have successfully demonstrated their procedure in human cells. It's believed that this research, along with other efforts, will pave the way for future clinical trials in human subjects.

The research results are online Oct. 24, in the journal Nature. Dr. Mitalipov also will present the results of his research at the American Society for Reproductive Medicine Conference in San Diego Oct. 24

The OHSU gene therapy method was initially devised through research in nonhuman primates led by Shoukhrat Mitalipov, Ph.D., associate scientist in the Division of Reproductive & Developmental Sciences at ONPRC, Oregon Stem Cell Center and OHSU School of Medicine departments of Obstetrics and Gynecology and Molecular and Medical Genetics.

The procedure was specifically developed to prevent diseases related to gene defects in the cell mitochondria. Mitalipov's previous work was published in the August 2009 edition of Nature. In the current study, Mitalipov, in collaboration with Paula Amato, M.D., associate professor of obstetrics and gynecology in the OHSU Center for Women's Health, demonstrated efficacy of this therapy in human gametes and embryos.

"Cell mitochondria contain genetic material just like the cell nucleus and these genes are passed from mother to infant," explained Mitalipov. "When certain mutations in mitochondrial DNA are present, a child can be born with severe conditions, including diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia and several other neurological diseases. Because mitochondrial-based genetic diseases are passed from one generation to the next, the risk of disease is often quite clear. The goal of this research is to develop a therapy to prevent transmission of these disease-causing gene mutations."

To conduct this research, Mitalipov and his colleagues obtained 106 human egg cells from study volunteers recruited through OHSU's Division of Fertility and Reproductive Endocrinology. The researchers then used a method developed in previous nonhuman primate studies, to transfer the nucleus from one cell to another. In effect, the researchers "swapped out" the cell cytoplasm, which contains the mitochondria. The egg cells were then fertilized to determine whether the transfer was a success and whether the cells developed normally. Upon inspection, it was demonstrated that it was possible to successfully replace mitochondrial DNA using this method.

"Using this process, we have shown that mutated DNA from the mitochondria can be replaced with healthy copies in human cells," explained Mitalipov. "While the human cells in our study were allowed to develop to the embryonic stem cell stage, this research shows that this gene therapy method may well be a viable alternative for preventing devastating diseases passed from mother to infant."

The current Nature paper also expanded upon the previously reported nonhuman primate work by demonstrating that the method was possible using frozen egg cells. Mitochondria were replaced in a frozen/thawed monkey egg cell, resulting in the birth of a healthy baby monkey named Chrysta.

The second portion of the study, which was completed at ONPRC, is also considered an important achievement because egg cells only remain viable for a short period of time after they are harvested from a donor. Therefore, for this therapy to be a viable option in the clinic, preservation through freezing likely is necessary so that both the donor cell and a mother's cell are viable at the time of the procedure.

While this form of therapy has yet to be approved in the United States, the United Kingdom is seriously considering its use for treating human patients at risk for mitochondria-based disease. It's believed that this most recent breakthrough, combined with earlier animal studies, will help inform that decision-making process.

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New gene therapy method tested in human cells ... and it works, researchers report

Public release date: 24-Oct-2012 [ | E-mail | Share ]

Contact: Jim Newman newmanj@ohsu.edu 503-494-8231 Oregon Health & Science University

PORTLAND, Ore. - Oregon Health & Science University's development of a new gene therapy method to prevent certain inherited diseases has reached a significant milestone. Researchers at the university's Oregon National Primate Research Center and the OHSU Department of Obstetrics & Gynecology have successfully demonstrated their procedure in human cells. It's believed that this research, along with other efforts, will pave the way for future clinical trials in human subjects.

The research results are online Wednesday, Oct. 24, in the highly respected journal Nature. Dr. Mitalipov also will present the results of his research at the American Society for Reproductive Medicine Conference in San Diego Oct. 24'.

The OHSU gene therapy method was initially devised through research in nonhuman primates led by Shoukhrat Mitalipov, Ph.D., associate scientist in the Division of Reproductive & Developmental Sciences at ONPRC, Oregon Stem Cell Center and OHSU School of Medicine departments of Obstetrics and Gynecology and Molecular and Medical Genetics.

The procedure was specifically developed to prevent diseases related to gene defects in the cell mitochondria. Mitalipov's previous work was published in the August 2009 edition of Nature. In the current study, Mitalipov, in collaboration with Paula Amato, M.D., associate professor of obstetrics and gynecology in the OHSU Center for Women's Health, demonstrated efficacy of this therapy in human gametes and embryos.

"Cell mitochondria contain genetic material just like the cell nucleus and these genes are passed from mother to infant," explained Mitalipov. "When certain mutations in mitochondrial DNA are present, a child can be born with severe conditions, including diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia and several other neurological diseases. Because mitochondrial-based genetic diseases are passed from one generation to the next, the risk of disease is often quite clear. The goal of this research is to develop a therapy to prevent transmission of these disease-causing gene mutations."

To conduct this research, Mitalipov and his colleagues obtained 106 human egg cells from study volunteers recruited through OHSU's Division of Fertility and Reproductive Endocrinology. The researchers then used a method developed in previous nonhuman primate studies, to transfer the nucleus from one cell to another. In effect, the researchers "swapped out" the cell cytoplasm, which contains the mitochondria. The egg cells were then fertilized to determine whether the transfer was a success and whether the cells developed normally. Upon inspection, it was demonstrated that it was possible to successfully replace mitochondrial DNA using this method.

"Using this process, we have shown that mutated DNA from the mitochondria can be replaced with healthy copies in human cells," explained Mitalipov. "While the human cells in our study only allowed to develop to the embryonic stem cell stage, this research shows that this gene therapy method may well be a viable alternative for preventing devastating diseases passed from mother to infant."

The current Nature paper also expanded upon the previously reported nonhuman primate work by demonstrating that the method was possible using frozen egg cells. Mitochondria were replaced in a frozen/thawed monkey egg cell, resulting in the birth of a healthy baby monkey named Chrysta.

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OHSU researchers test new gene therapy method in human cells... and it works

Published: Oct. 16, 2012 at 8:30 PM

EVANSTON, Ill., Oct. 16 (UPI) -- U.S. scientists say they've discovered how to control the shape of nanoparticles that can move DNA through the body to treat cancer and other diseases.

A gene therapy technique utilizing nanoparticles is significant in that it does not use a virus to carry DNA into cells, as some gene therapy strategies relying on viruses have posed health risks, researchers at Northwestern University and John Hopkins University reported.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," John Hopkins material science Professor Hai-Quan Mao said.

Mao, who has been developing non-viral nanoparticles for gene therapy for a decade, said a major breakthrough is the ability to "tune" the particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles.

The nanoparticles carry healthy snippets of DNA within protective polymer coatings and are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells, prompting the cells to produce functional proteins that combat disease.

View original post here:

Nanoparticles seen as gene therapy advance

Jen Esposito, 15, of Bedford, N.Y., and Sabrina Carrozzi, 15, of White Plaines, N.Y., takes worms, to see in a microscope during Dr. Bruce Nash, of the Cold Spring Harbor Laboratory, meets with Upper School classes to discuss gene therapy at Convent of the Sacred Heart on Monday, October 15, 2012. Convent of the Sacred Heart is the third school, and the first Connecticut-based school, to become a charter member of the Cold Spring Harbor genetics lab. Photo: Helen Neafsey / Greenwich Time | Buy This Photo

Jen Esposito, 15, of Bedford, N.Y., and Sabrina Carrozzi, 15, of...

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Sacred Heart partners with renowned N.Y. lab

ScienceDaily (Oct. 11, 2012) Researchers at the University of Illinois Hospital & Health Sciences System have identified a genetic signature that distinguishes patients with complicated sarcoidosis, an inflammatory lung disease that can be fatal, from patients with a more benign form of the disease. The gene signature could become the basis for a simple blood test.

Their findings are reported online in the journal PLOS ONE.

In sarcoidosis, tiny clumps of abnormal tissue form in organs of the body. These clusters of immune cells, called granulomas, cause inflammation. Sarcoidosis can occur in the lymph nodes, liver, eyes, skin or other tissues, but almost always also in the lungs. The cause of the disease is unknown. African Americans are at higher risk for the disease and for more severe cases.

"One of the perplexing aspects of this disease is that two thirds of the people who get sarcoidosis get better with only minimal therapy," says Dr. Joe G.N. "Skip" Garcia, vice president for health affairs at the University of Illinois and principle investigator on the study.

But one third of patients go on to develop complicated sarcoidosis -- neurologic sarcoidosis, cardiac sarcoidosis and progressive lung disease, Garcia said. Complicated sarcoidosis can leave patients with lung damage, and in a small percentage of cases the disease can be fatal.

The challenge, Garcia says, is that there is no difference in the clinical presentation between patients with simple sarcoidosis and those who will go on to develop more serious disease.

The researchers took blood from patients with simple and complicated sarcoidosis as well as patients without the disease to look for a pattern of gene expression unique to complicated sarcoidosis.

They were able to identify a distinct 20-gene pattern of gene expression that could reliably identify those most likely to progress to complicated sarcoidosis.

A 31-gene expression signature had been identified previously, but a smaller panel of genes makes the new test less expensive and more useful clinically, said Garcia.

"We are dedicated to looking for new insights as well as new therapies for sarcoidosis and hope to someday be able to identify people at risk for it ahead of time," Garcia said.

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New gene test flags risk of serious complications in sarcoidosis

Public release date: 12-Oct-2012 [ | E-mail | Share ]

Contact: Megan Fellman fellman@northwestern.edu 847-491-3115 Northwestern University

Researchers from Johns Hopkins and Northwestern universities have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.

This study, to be published in the Oct. 12 online edition of the journal Advanced Materials, is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," said Hai-Quan Mao, an associate professor of materials science and engineering in Johns Hopkins' Whiting School of Engineering.

Mao, co-corresponding author of the Advanced Materials article, has been developing nonviral nanoparticles for gene therapy for a decade. His approach involves compressing healthy snippets of DNA within protective polymer coatings. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.

A major advance in this work is that Mao and his colleagues reported that they were able to "tune" these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. "We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well," Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.

To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.

Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern's McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.

"Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change," Luijten said. "We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape."

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Scientists discover that shape matters in DNA nanoparticle therapy

ScienceDaily (Oct. 12, 2012) Researchers from Johns Hopkins and Northwestern universities have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.

This study, published in the Oct. 12 online edition of Advanced Materials, is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," said Hai-Quan Mao, an associate professor of materials science and engineering in Johns Hopkins' Whiting School of Engineering.

Mao, co-corresponding author of the Advanced Materials article, has been developing nonviral nanoparticles for gene therapy for a decade. His approach involves compressing healthy snippets of DNA within protective polymer coatings. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.

A major advance in this work is that Mao and his colleagues reported that they were able to "tune" these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. "We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well," Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.

To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.

Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern's McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.

"Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change," Luijten said. "We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape."

The use of computer models allowed Luijten's team to mimic traditional lab experiments at a far faster pace. These molecular dynamic simulations were performed on Quest, Northwestern's high-performance computing system. The computations were so complex that some of them required 96 computer processors working simultaneously for one month.

In their paper, the researchers also wanted to show the importance of particle shapes in delivering gene therapy. Team members conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: rods, worms and spheres.

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Shape matters in DNA nanoparticle therapy

ScienceDaily (Oct. 12, 2012) Researchers from Johns Hopkins and Northwestern universities have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.

This study, to be published in the Oct. 12 online edition of the journal Advanced Materials, is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," said Hai-Quan Mao, an associate professor of materials science and engineering in Johns Hopkins' Whiting School of Engineering.

Mao, co-corresponding author of the Advanced Materials article, has been developing nonviral nanoparticles for gene therapy for a decade. His approach involves compressing healthy snippets of DNA within protective polymer coatings. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.

A major advance in this work is that Mao and his colleagues reported that they were able to "tune" these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. "We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well," Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.

To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.

Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern's McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.

"Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change," Luijten said. "We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape."

The use of computer models allowed Luijten's team to mimic traditional lab experiments at a far faster pace. These molecular dynamic simulations were performed on Quest, Northwestern's high-performance computing system. The computations were so complex that some of them required 96 computer processors working simultaneously for one month.

In their paper, the researchers also wanted to show the importance of particle shapes in delivering gene therapy. Team members conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: rods, worms and spheres.

Read this article:

Shape matters in DNA nanoparticle therapy: Particles could become a safer, more effective delivery vehicle for gene ...

Important BYU research debunks the idea of "junk DNA"

The human body contains approximately 50 trillion cells whose length of DNA content compares to 528 million donuts wrapped around the earth 2,500 times.

Until recently, scientists thought 95 percent of that DNA was junk and had no function. BYU microbiology professor Steven Johnson and one of his undergraduate assistants, Elliot Winters, participated in a worldwide collaborative research project, the ENCODE Projectconcluded 80 percent of a persons DNA does perform an important function.

Its the culmination of this international consortium saying all this DNA that we thought didnt have a function actually has a function or has something going on, Johnson said. We dont know exactly what is going on, but its not just junk that is sitting there with no purpose.

The collaborative research project, the ENCODE Project, provides a database of information to those performing genetic research. The research was published in Genome Research, and Johnson and Winters are listed as co-authors.

[/media-credit] Mentored research provides exceptional opportunities for BYU students

We told them exactly how we wanted the cells prepared, and they sent them to us frozen, Johnson said. I taught my undergraduate student, Elliot Winters, this technique that Id developed. Over a course of about four months, we were able to get it to work just right and isolate just the DNA that we wanted to with the nucleosomes.

Winters is not alone in doing mentored undergraduate research atBYU. According to the BYU website,the university gave $1.4 million to 71 faculty members specifically for projects involving undergraduates. Winters identifies his research experience as one of the most important parts of his BYU education.

The reason I started doing it is because I wanted to strengthen my application for medical school, Winters said. Looking back on it, it was one of the most valuable parts of my education.

Winters is only one of many students Johnson employs in his labs. Colton Kempton, a third-year masters student from Safford, Ariz., is currently working with Johnson on more DNA research related to gene therapy.

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DNA research: Contribution to gene therapy - Important BYU research debunks the idea of "junk DNA"

ANN ARBOR, Mich.--(BUSINESS WIRE)--

RetroSense Therapeutics, a biotechnology company dedicated to developing gene therapy approaches to vision restoration welcomes Steven Bramer, PhD to its senior management team as Chief Development Officer.

Dr. Bramer brings a host of high-value skills to the team in drug development, business development, and beyond. As an all-around-athlete having great drug development experience, with an emphasis on ocular therapeutics, he is an outstanding complement to our executive team, stated Sean Ainsworth, CEO and founder of RetroSense Therapeutics.

Dr. Steven Bramer has over 26 years of drug development experience. He has held positions in global companies where he contributed substantially to all stages of development for drugs, biologics, tissues, combination products, and devices. His experience covers a broad range of therapeutic areas, including ophthalmology, and he has dealt extensively with regulatory agencies in the US and abroad. Dr. Bramer has served in leadership roles throughout most of his career, leading departments, teams, and initiatives successfully including his role as the Chief Drug Development Officer at the Foundation Fighting Blindness.

I had the privilege of being introduced to the team at RetroSense while was the Chief Drug Development Officer at the Foundation Fighting Blindness. Of the numerous projects I had the pleasure of evaluating in that role, RetroSenses optogenetic therapy stood out as an excellent opportunity to restore vision. What is unique and promising about this approach is the potential to restore vision in patients who have lost the function of their rods and cones due to a wide variety of causes. I am excited to work with RetroSense to bring this technology to the clinic and ultimately to the patients whose lives have been impacted by vision loss.

Dr. Bramer will play a pivotal role in bringing RetroSenses lead product, RST-001, into the clinic for the treatment of retinal degenerative conditions, such as retinitis pigmentosa and dry age-related macular degeneration.

Dr. Bramer holds an AS degree in Biology from Delhi College, BS degree in Animal Science from Cornell University, and has completed a MS program in Pathology and a Ph.D. in Pharmaceutics from The Ohio State University.

About RetroSense Therapeutics

RetroSense Therapeutics is a biotechnology company developing a game-changing gene therapy to restore vision in patients suffering from blindness due to retinitis pigmentosa (RP) and advanced dry age-related macular degeneration (advanced dry-AMD). There are currently no FDA approved therapies to improve or restore vision in patients with these retinal degenerative conditions. RetroSense is led by a team of seasoned veterans with deep experience in taking products from the discovery stage through to the clinic. For more information about RetroSense, visit http://www.retro-sense.com/.

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RetroSense Therapeutics Welcomes Dr. Steven Bramer as Chief Development Officer

Newswise (Sioux Falls, SD) - A study conducted by Sanford Healths John Lee, MD, and Etubics Corporation that uses a vaccine to suppress human papilloma virus (HPV) has been published by Cancer Gene Therapy.

The study, "A non-oncogenic HPV 16 E6/E7 vaccine enhances treatment of HPV expressing tumors," appears in the October issue of the peer-reviewed publication.

HPV is the leading cause of more than 90 percent of cervical cancers and 25 percent of head and neck cancers. Currently, no HPV therapeutic vaccine is effective at treating established tumors, despite its success with preventing HPV infection.

Dr. Lee and his team used an Etubics drug (Ad5 [E1-, E2b-]) in conjunction with chemotherapy and radiation to successfully improve long-term survival of animals expressing HPV. Etubics drug induces immune response in circumstances where it is suppressed due to pre-existing conditions.

This article provides a pre-clinical rationale to initiate testing of a therapeutic vaccine in humans, said Dr. Lee. The approaches enhance HPV specific immune clearance in conjunction with standard of care chemo-radiation, with the potential for improving the survival advantage for patients by 30 percent.

Etubics is a clinical stage bio-pharmaceutical company with a proprietary platform vaccine technology that delivers a long lasting "active" immune response against diseases.

"At Etubics, we strive to utilize our Etubics Platform to create immunotherapies that target difficult-to-treat cancers, said Dr. Frank Jones, founder, chairman and CEO at Etubics. We are excited to be a part of this groundbreaking research on an HPV immunotherapy at Sanford Research and help to come one step closer to a meaningful therapy for HPV induced cancers."

Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research.

About Sanford Research/USD Sanford Research/USD is a non-profit research organization formed between Sanford Health and the University of South Dakota. Sanford Health is an integrated health system headquartered in Fargo, ND and Sioux Falls, SD and represents the largest, rural, not-for-profit healthcare system in the nation with a presence in 111 communities, eight states and three countries. In 2007, a transformational gift of $400 million by Denny Sanford provided for an expansion of childrens and research initiatives, specifically finding a cure for type 1 diabetes, and has given Sanford Research significant momentum in its goal of becoming one of the premiere research institutions in the United States and the world. Most recently, a subsequent gift of $100 million by Mr. Sanford has paved the way to establish Edith Sanford Breast Cancer Research.

With a team of more than 200 researchers, Sanford Research comprises several research centers, including Childrens Health Research, Edith Sanford Breast Cancer, Cancer Biology, Cardiovascular Health, Center for Health Outcomes and Prevention, and the National Institute for Athletic Health and Performance (NIAHP).

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Sanford Researcher Leads Published Study on HPV Vaccine

Is gene therapy finally becoming a reality? The European Commission is poised to authorize, for the first time in the Western world, the commercialization of a gene-therapy product. Called Glybera (alipogene tiparvovec), it is designed to treat a rare genetic defect involved in fat metabolism.

Success has been a long time coming. Gene therapy was first administered more than 20 years ago, to a child who had a rare disorder of the immune system called adenosine deaminase (ADA) deficiency. Since then, it has struggled to find its place in medicine amid a roller coaster of successes and setbacks, hype and scepticism that has little precedent in modern times. Although the approval of Glybera is a positive move, it is unlikely to herald a new age of gene therapies not without significant changes to the system. It is no coincidence that no gene therapy has yet been approved in the United States and that no other gene-therapy product is being considered by regulators in Europe.

Here is why. The design, development and manufacture of products such as Glybera a virus engineered to carry a correct copy of the defective gene is complex and done mostly in academic centres. Yet legislation introduced in the past decade in Europe and the United States demands that these products be produced under the same rules that cover conventional drugs, in establishments operated with industry-like standards and certified by government agencies.

This is a formidable challenge for academic centres, which tend to lack the necessary human and financial resources. So why is the development of gene therapy focused there, and not in industry, which seems better suited?

The first reason is the financial uncertainty generated by the complex, confused and poorly harmonized regulatory environment as the history of Glybera shows. At first, the application for its authorization received a negative opinion from two committees at the European Medicines Agency (EMA): the Committee for Advanced Therapies (CAT) and the Committee for Human Medicinal Products for Human Use (CHMP). Only when another body, the Standing Committee of the European Commission, asked the EMA to reconsider the application in a restricted indication did the CHMP eventually recommend approval under exceptional circumstances, requiring post-marketing studies and the set-up of a restricted-access programme. The Dutch firm Amsterdam Molecular Therapeutics, the inventor of Glybera, did not survive the process, and became known as uniQure after refinancing.

Lack of resources is a second reason. For many years, the drug industry stayed away from gene therapy, perceiving it as a dangerous technology of dubious efficacy that was too complex to develop and targeted too small a market.

There are some positive signs, because this last perception, at least, is changing: the industry now recognizes that rare diseases and orphan-drug legislation provide attractive opportunities. Some recombinant proteins and monoclonal antibodies originally developed as orphan drugs have been repurposed for larger indications.

The industry now recognizes that rare diseases and orphan-drug legislation provide attractive opportunities.

An example of how academia and industry could cooperate comes from the recent alliance between the drug giant GlaxoSmithKline (GSK) in London, and the charity-funded San Rafaelle Telethon Institute for Gene Therapy (TIGET) in Milan, Italy. GSK gained an exclusive licence to develop and commercialize the ADA treatment, and will co-develop with TIGET gene therapies for six more genetic diseases. The contribution of public or charity-funded organizations in early development phases lowers the cost and risk of investing in diseases with a tiny market, and gives the industry access to technologies that can be expanded to more profitable applications, thereby repaying the investment and allowing resources to be fed back into rare diseases. Unfortunately, promising therapies for hundreds of orphan diseases are unlikely to attract similar industrial interest.

So, how do we ensure that scientists will continue to develop such treatments? Should they all turn to the hospital exemption, which permits experimental therapies to be manufactured and used under the responsibility of a physician without regulatory supervision?

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Gene therapies need new development models

SILVER SPRING, Md. and SINGAPORE, Oct. 2, 2012 (GLOBE NEWSWIRE) -- Nuvilex, Inc. (NVLX), an international biotechnology provider of cell and gene therapy solutions, announced today its wholly-owned subsidiary, Austrianova Singapore Pte Ltd (ASPL) will attend this year's AusBiotech event.

The annual AusBiotech event this year will be held from October 30 - November 2 at the Melbourne Convention and Exhibition Centre, Melbourne, Australia. It has earned a reputation as the industry's premier biotechnology conference for the Asia Pacific region and has successfully expanded its relevance to the Australian and International Biotechnology industries by attracting more than 1100 participants from over 20 countries.

Dr Brian Salmons, CEO of ASPL said, "AusBiotech has grown in stature over the past several years. In prior years, we entered agreements with companies and found it to be one of the most valuable events for networking with new contacts. We anticipate meeting with companies with proprietary therapeutic cells, such as stem cells, that can leverage their technology with our Cell-in-a-Box(R) delivery system. We believe the new contacts we make will expand our customer base and increase the use of cell and gene therapy for making therapeutic products and treating diseases. We will also be promoting our Bac-in-a-Box(R) technology for the first time at this meeting and anticipate generating interest around its potential."

The Chief Executive of Nuvilex, Dr. Robert Ryan, stated "Attendance at this important biotech event in Australia and within easy reach of Southeast Asia will enable us to have increased exposure for our Cell-in-a-Box(R) and Bac-in-a-Box(R) live cell encapsulation technology and to showcase its immense versatility, thus providing our companies greater visibility at a time that such capabilities are becoming more important in the marketplace. It is our goal to bring more projects to fruition from this meeting as more companies today are looking to bring cellular-based therapy and product creation from the drawing board to reality and into regular use."

About Nuvilex

Nuvilex, Inc. (NVLX) is an international biotechnology provider of live therapeutically valuable, encapsulated cells and services for research and medicine. A great deal of work is ongoing to move Nuvilex and its Austrianova Singapore subsidiary forward. This was clearly apparent during Dr. Ryan's trip to Singapore and the advent of new developments in the company as a whole. Our company's own offerings will include cancer, diabetes, other treatments and capabilities using the company's cell and gene therapy expertise and live-cell encapsulation technology.

The Nuvilex, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=13494

Safe Harbor Statement

This press release contains forward-looking statements described within the 1995 Private Securities Litigation Reform Act involving risks and uncertainties including product demand, market competition, and meeting current or future plans which may cause actual results, events, and performances, expressed or implied, to vary and/or differ from those contemplated or predicted. Investors should study and understand all risks before making an investment decision. Readers are recommended not to place undue reliance on forward-looking statements or information. Nuvilex is not obliged to publicly release revisions to any forward-looking statement, reflect events or circumstances afterward, or disclose unanticipated occurrences, except as required under applicable laws.

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Nuvilex Subsidiary Austrianova Singapore to Participate in AusBiotech 2012

Newly published obesity research coming out of the University of Alberta has touched upon a possible avenue for obesity reduction.

Jason Dyck, a U of A medical researcher and professor, is the lead researcher for the study, which may be close to finding a new way to combat obesity.

In this study, mice are fed a high-fat, high-sugar diet the type of diet that generally leads to obesity. They then have adiponectin DNA injected into their leg muscles.

Adiponectin, secreted by fat cells, is known to have heart-protective and weight-regulating properties. If fat cells get too large, they no longer secrete normal amounts of the hormone-like substance.

What Dyck and his research team have found is the mice receiving this gene therapy start to produce adiponectin in higher levels, thus exhibiting weight loss.

Regardless of its high fat diet, the mouse is acting like a skinny mouse, Dyck said.

Treating obesity as an illness has raised some eyebrows in the Edmonton community, including radio show host Yukon Jack who said, if being fat is a disease, then playing bingo is a professional sport.

Dyck says this viewpoint probably reflects the majority of opinions about obesity. However, many doctors and medical professonals consider obesity a disease.

But this type of research has broader applications than just exercise-free weight loss. Obesity is closely linked with the loss of insulin sensitivity observed in Type 2 Diabetes.

What we are seeing with this gene therapy is a significant, but modest effect on weight gain. Despite only a slight reduction in weight gain, we are still seeing almost a complete restoration of insulin sensitivity, Dyck said.

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Gene therapy a possible option for obesity

SILVER SPRING, Md., Sept. 27, 2012 (GLOBE NEWSWIRE) -- Nuvilex, Inc. (NVLX), an international biotechnology provider of cell and gene therapy solutions, announced today that Austrianova Singapore Pte Ltd (ASPL) will reveal confirmatory findings from a second phase 2 pancreatic cancer clinical trial that used the encapsulated cytochrome P450 expressing cells followed by chemotherapy to treat pancreatic cancer at the International Society for Cell and Gene Therapy (ISCGT) meeting next week.

ASPL's Chief Operating Officer, Dr John Dangerfield, will be presenting the clinical data at the upcoming ISCGT meeting in Singapore, October 4-7. The ISCGT has previously organized numerous meetings in the US, England, France, Germany, Italy, Ireland, China, India and Egypt. The ISCGT works in close collaboration with national societies and organizations, as well as local clinicians, to promote cell and gene therapies for use in cancer therapy advancement and treatment. Council members of the ISCGT include leading experts and peers that have made major contributions to advance cell and gene therapies.

Dr. Brian Salmons, CEO of ASPL stated, "We determined that the ISCGT would be an important forum for presenting this additional data. The value for bringing this to ISCGT is a result of how they have been championing major developments in cell and gene therapy based approaches to treat cancer over the past several years. We are very pleased to have Dr. Dangerfield representing us as a speaker at this year's conference and presenting this important advancement to our work."

Dr. Robert F. Ryan, CEO of Nuvilex said, "The most important aspect of what will be presented at ISCGT is that safety and mean survival pancreatic cancer trial data being shown has not previously appeared in the public domain. Therefore, we are very pleased that this data will be shown at this conference. The data that Dr. Dangerfield will present confirms and extends the previous clinical trial results - namely that our encapsulated cell therapy, when used in combination with the appropriate chemotherapy, is safe, well-tolerated and efficacious for treating pancreatic cancer."

About Nuvilex

Nuvilex, Inc. (NVLX) is an international biotechnology provider of live therapeutically valuable, encapsulated cells and services for research and medicine. Substantial progress in multiple areas will be providing the Company with increased potential and we look forward to bringing those forward shortly. Our company's clinical offerings will include cancer, diabetes and other treatments using the company's cell and gene therapy expertise and live-cell encapsulation technology.

The Nuvilex, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=13494

Safe Harbor Statement

This press release contains forward-looking statements described within the 1995 Private Securities Litigation Reform Act involving risks and uncertainties including product demand, market competition, and meeting current or future plans which may cause actual results, events, and performances, expressed or implied, to vary and/or differ from those contemplated or predicted. Investors should study and understand all risks before making an investment decision. Readers are recommended not to place undue reliance on forward-looking statements or information. Nuvilex is not obliged to publicly release revisions to any forward-looking statement, reflect events or circumstances afterward, or disclose unanticipated occurrences, except as required under applicable laws.

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Nuvilex's Subsidiary, Austrianova Singapore, to Provide Confirmatory Findings From Additional Pancreatic Cancer Trial ...

According to a new study on adiponectin and raspberry ketone, obesity may be treated by regulating the levels of a key hormone in the body.(PRWEB) September 25, 2012 Researchers at the University of Alberta have reported that a specific type of gene therapy involving Adiponectin and Raspberry Ketone can actually help fight obesity.The study from The Journal of Nutrition & Diabetes concluded that ...

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Adiponectin Gene Therapy May Help Fight Obesity

A new way of using gene therapy to help those fighting the battle of the bulge has been discovered by University of Alberta researchers.

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Allison Salz

Public release date: 11-Sep-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-435-9457 University of California - Los Angeles Health Sciences

UCLA stem cell researchers have found that a gene therapy regimen can safely restore immune systems to children with so-called "Bubble Boy" disease, a life threatening condition that if left untreated can be fatal within one to two years.

In the 11-year study, researchers were able to test two therapy regimens for 10 children with ADA-deficient severe combined immunodeficiency (SCID). During the study, they refined their approach to include a light dose of chemotherapy to help remove many of the blood stem cells in the bone marrow that are not creating an enzyme called adenosine deaminase (ADA), which is critical for the production and survival of healthy white blood cells, said study senior Dr. Donald Kohn, a professor of pediatrics and of microbiology, immunology, and molecular genetics in Life Sciences and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The refined gene therapy and chemotherapy regimen proved superior to the other method tested in the study, restoring immune function to three of the six children who received it, Kohn said. Going forward, an even further refined regimen using a different type of virus delivery system will be studied in the next phase of the study, which already has enrolled eight of the 10 patients needed.

The study appears Aug. 30 in the advance online issue of the peer-reviewed journal Blood.

"We were very happy that in the human trials we were able to see a benefit in the patients after we modified the protocol," Kohn said. "Doctors treating ADA-deficient SCID have had too few options for too long, and we hope this will provide them with an efficient and effective treatment for this devastating disease."

Children born with SCID, an inherited immunodeficiency, are generally diagnosed at about six months. They are extremely vulnerable to infectious diseases and don't grow well. Chronic diarrhea, ear infections, recurrent pneumonia and profuse oral candidiasis commonly occur in these children. SCID cases occur in about 1 of 100,000 births

Currently, the only treatment for ADA-deficient SCID calls for injecting the patients twice a week with the necessary enzyme, Kohn said, a life-long process that is very expensive and often doesn't return the immune system to optimal levels. These patients also can undergo bone marrow transplants from matched siblings, but matches can be very rare.

About 15 percent of all SCID patients are ADA-deficient. Kohn and his team used a virus delivery system that he had developed in his lab in the 1990s to restore the gene that produces the missing enzyme necessary for a healthy immune system. To date, about 40 children with SCID have received gene therapy in clinical trials around the world, Kohn said.

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UCLA stem cell researchers use gene therapy to restore immune systems in 'bubble babies'

ScienceDaily (Sep. 11, 2012) UCLA stem cell researchers have found that a gene therapy regimen can safely restore immune systems to children with so-called "Bubble Boy" disease, a life threatening condition that if left untreated can be fatal within one to two years.

In the 11-year study, researchers were able to test two therapy regimens for 10 children with ADA-deficient severe combined immunodeficiency (SCID). During the study, they refined their approach to include a light dose of chemotherapy to help remove many of the blood stem cells in the bone marrow that are not creating an enzyme called adenosine deaminase (ADA), which is critical for the production and survival of healthy white blood cells, said study senior Dr. Donald Kohn, a professor of pediatrics and of microbiology, immunology, and molecular genetics in Life Sciences and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The refined gene therapy and chemotherapy regimen proved superior to the other method tested in the study, restoring immune function to three of the six children who received it, Kohn said. Going forward, an even further refined regimen using a different type of virus delivery system will be studied in the next phase of the study, which already has enrolled eight of the 10 patients needed.

The study appears Aug. 30 in the advance online issue of the peer-reviewed journal Blood.

"We were very happy that in the human trials we were able to see a benefit in the patients after we modified the protocol," Kohn said. "Doctors treating ADA-deficient SCID have had too few options for too long, and we hope this will provide them with an efficient and effective treatment for this devastating disease."

Children born with SCID, an inherited immunodeficiency, are generally diagnosed at about six months. They are extremely vulnerable to infectious diseases and don't grow well. Chronic diarrhea, ear infections, recurrent pneumonia and profuse oral candidiasis commonly occur in these children. SCID cases occur in about 1 of 100,000 births

Currently, the only treatment for ADA-deficient SCID calls for injecting the patients twice a week with the necessary enzyme, Kohn said, a life-long process that is very expensive and often doesn't return the immune system to optimal levels. These patients also can undergo bone marrow transplants from matched siblings, but matches can be very rare.

About 15 percent of all SCID patients are ADA-deficient. Kohn and his team used a virus delivery system that he had developed in his lab in the 1990s to restore the gene that produces the missing enzyme necessary for a healthy immune system. To date, about 40 children with SCID have received gene therapy in clinical trials around the world, Kohn said.

Two slightly different viral vectors were tested in the study, each modified to deliver healthy ADA genes into the bone marrow cells of the patients so the needed enzyme could be produced and make up for the cells that don't have the gene. Four of the 10 patients in the study remained on their enzyme replacement therapy during the gene therapy study. There were no side effects, but their immune systems were not sufficiently restored, Kohn said.

In the next six patients, the enzyme therapy was stopped and a small dose of chemotherapy was given before starting the gene therapy to deplete the ADA-deficient stem cells in their bone marrow. Of those patients, half had their immune systems restored. The human findings confirmed another study, also published recently in Blood by Kohn and UCLA colleague Dr. Denise Carbonaro-Sarracino, which tested the techniques in parallel, using a mouse model of ADA-deficient SCID.

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Stem cell researchers use gene therapy to restore immune systems in 'Bubble Boy' disease

ScienceDaily (Sep. 11, 2012) By including chemotherapy as a conditioning regimen prior to treatment, researchers have developed a refined gene therapy approach that safely and effectively restores the immune system of children with a form of severe combined immunodeficiency (SCID), according to a study published online September 11 in Blood, the Journal of the American Society of Hematology (ASH).

SCID is a group of rare and debilitating genetic disorders that affect the normal development of the immune system in newborns. Infants with SCID are prone to serious, life-threatening infections within the first few months of life and require extensive treatment for survival beyond infancy.

Adenosine deaminase (ADA) deficiency, which accounts for approximately 15 percent of all SCID cases, develops when a gene mutation prohibits the production of ADA, an enzyme that breaks down toxic molecules that can accumulate to harmful levels and kill lymphocytes, the specialized white blood cells that help make up the immune system. In its absence, infants with ADA-deficient SCID lack almost all immune defenses and their condition is almost always fatal within two years if left untreated. Standard treatment for ADA-deficient SCID is a hematopoietic stem cell transplant (HSCT) from a sibling or related donor; however, finding a matched donor can be difficult and transplants can carry significant risks. An alternate treatment method, enzyme replacement therapy (ERT), involves regular injections of the ADA enzyme to maintain the immune system and can help restore immune function; however, the treatments are extremely expensive and painful for the young patients and the effects are often only temporary.

Given the limitations of HSCT and ERT, in the 1990s researchers began investigating the efficacy of gene therapy for ADA-deficient SCID. They discovered that they could "correct" the function of a mutated gene by adding a healthy copy into the cells of the body that help fight infectious diseases. Since then, there have been significant advances in gene therapy for SCID, yet successful gene therapy in patients with ADA-deficient SCID has been seen in only a small series of children due to the difficulty of introducing a healthy ADA gene into bone marrow stem cells and to engraft these cells back into the patients.

"Although the basic steps of gene therapy for patients with SCID have been known for a while, technical and clinical challenges still exist and we wanted to find an optimized gene therapy protocol to restore immunity for young children with ADA-deficient SCID," said Fabio Candotti, MD, one of the study's senior authors, senior investigator in the Genetics and Molecular Biology Branch of the National Human Genome Research Institute at the National Institutes of Health, and chair of the ASH Scientific Committee on Immunology and Host Defense.

To determine whether an enhanced gene therapy approach would improve immunity in children with ADA-deficient SCID, the teams of Dr. Candotti and Donald B. Kohn, MD, director of the Human Gene Medicine Program at the University of California, Los Angeles (UCLA), Professor of Pediatrics and of Microbiology, Immunology, and Molecular Genetics, and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, conducted a clinical trial in 10 patients with the disorder. For the first time, Drs. Candotti and Kohn and their team of investigators compared two different retroviral vectors, MND-ADA and GCsapM-ADA, to transport normal ADA genes into the young patients' bone marrow stem cells as well as two different treatment plans in preparation for receiving gene therapy. Following therapy, investigators found that more bone marrow stem cells were marked with the MND-ADA vector, demonstrating its superiority over the GCsapM-ADA vector.

The investigators also sought to determine whether providing a low dose of chemotherapy prior to gene therapy, known as a pre-transplant conditioning regimen, would successfully deplete the young patients' bone marrow stem cells and make room for gene-corrected stem cells. In four patients, gene therapy was performed without chemotherapy, and the patients remained on ERT throughout the entire procedure to evaluate the efficiency of ERT combined with gene therapy. While these patients did not experience any adverse effects, they also did not experience a significant increase in their levels of the ADA enzyme. They also maintained low absolute lymphocyte counts (ALC) and minimal immune system function, leading the researchers to believe that ERT may weaken the therapy's effect by diluting the number of gene-corrected lymphocytes.

The remaining six patients were treated with the chemotherapy drug busulfan prior to gene therapy and ERT was discontinued prior to the gene therapy procedure. A significant increase in ADA was observed in all six patients; half of them remain off of ERT with partial immune reconstitution -- findings that support results from prior trials in Italy and the United Kingdom using chemotherapy prior to gene therapy and discontinuting ERT. While the ALC of all six patients declined sharply in the first few months due to combined effects of busulfan administration and ERT withdrawal, their counts increased from six to 24 months, even in the three patients that remained off of ERT. After adjusting the chemotherapy dosage, investigators were able to determine an optimal level for enhancing the efficacy of the gene-therapy-corrected cells with minimal toxicity.

This study is the first to detail comparisons of ADA-deficient SCID patient outcomes between those treated with gene therapy who have not received pre-transplant conditioning while continuing to receive ERT with those receiving pre-transplant conditioning without the administration of ERT. This study is also the first to compare two different viral vectors to transport normal ADA genes into patient bone marrow.

"We were very happy that in this trial we were able to see a benefit in the patients after we modified the protocol," said Dr. Kohn. "Doctors treating ADA-deficient SCID have had too few options for too long, and we hope this will provide them with an efficient and effective treatment for this devastating disease."

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Gene therapy technique for children with immune disorder improved