SAN DIEGO, Jan. 29, 2013 /PRNewswire/ --Cardium Therapeutics (NYSE MKT: CXM) today announced a presentation at the 2013 Phacilitate Annual Cell & Gene Therapy Forum in Washington, DC. The Company's presentation, "Optimizing Phase III Trial Design for Generx (Ad5FGF-4)" by Cardium's Chief Scientific Officer, Gabor M. Rubanyi, M.D., Ph.D. outlined the current scientific knowledge about the mechanistic basis of adaptive coronary collateral growth, the biological processes to be targeted by therapeutic angiogenesis, and discussed the lessons learned during the past decade of the Company's Generx clinical development program. The presentation is available for viewing at http://www.cardiumthx.com/generx.html.

(Logo: http://photos.prnewswire.com/prnh/20051018/CARDIUMLOGO)

"The presentation yesterday reviewed new techniques that have been implemented to optimize our international Phase 3 ASPIRE clinical study for the Company's Generx (Ad5FGF-4) DNA-based angiogenic growth factor drug candidate, including: (1) diagnostic identification of patients likely to be more responsive to angiogenic therapy; (2) new balloon catheter-based delivery methods designed to boost adenovector gene delivery and enhance angiogenic growth factor efficiency; and (3) selection of relevant clinical endpoints which may be useful in future clinical studies and help advance the field of therapeutic angiogenesis," stated Christopher J. Reinhard, Cardium's Chairman and CEO.

Generx is an interventional cardiology-focused product candidate that is being developed to offer a one-time, non-surgical option for the treatment of a medical condition termed cardiac microvascular insufficiency (CMI) in patients with myocardial ischemia and symptomatic chronic stable angina pectoris due to coronary artery disease. Patients with CMI have had an insufficient angiogenic response to their current disease state and may benefit from a biological therapy that enhances cardiac perfusion through the facilitation of collateral vessel formation. Currently, patient inclusion in the ASPIRE study requires evidence of stress induced reversible myocardial ischemia as measured by SPECT imaging. The goal of the Company's Generx product candidate is to improve blood flow to the heart muscle by promoting and enhancing cardiac perfusion through the enlargement of pre-existing collateral arterioles (arteriogenesis) and the formation of new capillary vessels (angiogenesis). Various catheter-based imaging diagnostics including fractional flow reserve and washout collaterometry could enhance the clinical adoption of this non-surgical therapeutic angiogenesis approach following initial registration.

Cardium's extensive preclinical and clinical studies have been instrumental in identifying cardiac ischemia as a key facilitator of non-surgical DNA-based angiogenic therapy. Improved adenovector administration methods combine non-surgical, percutaneous balloon catheter-based delivery to transiently induce ischemia together with the use of nitroglycerin to enhance vector uptake. By increasing cell transfection efficiency and reaching both the peri-ischemic regions and pre-existing collaterals in the heart, this modified approach offers the potential to effectively simulate both angiogenesis and arteriogenesis to bring about improved blood flow. Cardium's new delivery techniques are also designed to provide uniform Generx uptake, to reduce response variability and to allow for the potential treatment of patients with a broader range of associated coronary artery disease.

Cardium has modified the primary endpoint of the ASPIRE clinical study from the traditional measure of improvement in treadmill exercise time (ETT) to a more objective efficacy endpoint of reduction in reversible perfusion deficit based on SPECT myocardial perfusion imaging. Similar to mechanical/surgical cardiac revascularization approaches, the goal of Generx treatment is to improve myocardial perfusion (blood flow). SPECT myocardial perfusion imaging can be used to quantitatively evaluate Generx's effectiveness by measuring improved myocardial blood flow under stress, a key prognostic indicator that is associated with the regenerative process of new collateral vessel formation in and around the regions of ischemia. While walking time during ETT has been a traditional efficacy measure of anti-anginal drugs, it is based on a subjective assessment of chest pain (angina pectoris), does not directly measure improvements in cardiac blood flow, and can be affected by other variables. Positive results from the prior Phase 2a clinical study (Grines et al., J Am Coll Cardiol 2003; 42:1339-47) showed that Generx improved myocardial blood flow in the ischemic region of the hearts of patients following a single intracoronary infusion as measured by the objective efficacy endpoint of SPECT imaging. The observed treatment effect for patients receiving Generx was similar in magnitude to that reported in the literature for patients undergoing angioplasty/stent or revascularization procedures with reversible perfusion defects of comparable size at one year following these procedures.

ASPIRE Study

The ASPIRE study is a 100-patient, randomized and controlled multi-center study currently enrolling patients at up to eight leading cardiology centers in the Russian Federation. The ASPIRE study is designed to further evaluate the safety and effectiveness of Cardium's Generx DNA-based angiogenic product candidate, which has already been tested in clinical studies involving 650 patients at more than one hundred medical centers in the U.S., Europe and elsewhere. The efficacy of Generx is being quantitatively assessed using rest and stress SPECT (Single-Photon Emission Computed Tomography) myocardial imaging to measure improvements in microvascular cardiac perfusion following a one-time, non-surgical, catheter-based administration of Generx. The Cedars-Sinai Medical Center Nuclear Cardiology Core Laboratory in Los Angeles, California, is the central core lab for the study and is responsible for the analysis of SPECT myocardial imaging data electronically transmitted from the Russian medical centers participating in the ASPIRE study. The Russian Health Authority has assigned Generx the therapeutic drug trade name of Cardionovo for marketing and sales in Russia.

An independent long-term prospective study published in Circulation (Meier et al, Circ. 2007; 116:975-983) provided key evidence indicating that men and women with more recruitable collateral circulation have a better chance of surviving a heart attack than patients who have less developed collateral circulation. This important study quantitatively evaluated coronary collateral blood flow in 845 patients with coronary artery disease during a 10-year follow-up period and showed that long-term cardiac mortality was approximately 66% lower in patients with a well-developed coronary collateral network (p=0.019). For the first time, this study showed the importance of collateral circulation beyond simply the relief of angina and provided further support of the potential for long term benefits from angiogenic therapy.

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Cardium Announces Presentaton at The 2013 Cell & Gene Therapy Forum

Gene Therapy OA Video v1

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Gene Therapy OA Video v1 - Video

Ophthalmology: Gene Therapy Research -- Katherine Wert, MS
Katherine Wert, Ph.D. Candidate at the Columbia University College of Physicians and Surgeons, discusses the role that gene therapy will play in the future to help patients suffering from eye disorders.

By: newyorkpresbyterian

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Ophthalmology: Gene Therapy Research -- Katherine Wert, MS - Video

Ophthalmology: Gene Therapy Clinical Trials -- Katherine Wert, MS
Katherine Wert, Ph.D. Candidate at the Columbia University College of Physicians and Surgeons, discusses the gene therapy clinical trials being run at NewYork-Presbyterian.

By: newyorkpresbyterian

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Ophthalmology: Gene Therapy Clinical Trials -- Katherine Wert, MS - Video

Public release date: 24-Jan-2013 [ | E-mail | Share ]

Contact: Gregory Harris gregory.harris@albertahealthservices.ca 403-619-3108 Alberta Health Services

CALGARY Researchers in Calgary have launched the first gene therapy clinical trial in the world for Fabry disease, a rare inherited enzyme deficiency that can shorten the lifespan of people who have it by as much as 40 years.

Researchers will first remove a quantity of stem cells from a Fabry patient's blood. Then a working copy of a new gene will be inserted into the stem cells using a specially engineered virus. During the final phase of the trial, researchers hope to transplant these stem cells back into the donor patient and the new, working copy of the gene will make the missing enzyme.

The clinical trial has been prompted by promising gene therapy results in mice performed in the laboratory of Dr. Jeffrey Medin at the University Health Network in Toronto. Dr. Medin is the principal investigator of the pan-Canada team grant that is supporting this trial.

"We hope this will one day become a form of treatment that effectively cures Fabry disease," says Dr. Aneal Khan, a medical geneticist based at Alberta Children's Hospital, who is leading the Calgary segment of the national project.

"It could also help establish a platform on which we can create gene therapies for other illnesses and establish Calgary as a national leader in this experimental field of interventional genetics."

Although several gene therapies have been used in Canada for cancer, this study will be the first in the country to test a gene therapy for an inherited metabolic disorder.

People with Fabry disease have a change in a gene called GLA and can't make enough enzyme to break down a fatty substance called Gb3. The build-up of Gb3 can lead to problems in the kidneys, heart and brain. About 400 Canadians, including 25 Calgarians, have Fabry disease.

Although the project is headquartered in Toronto, physicians and scientists in Calgary will play a major role in the clinical trial. In particular, the lab at Foothills Medical Centre in Calgary has specialized expertise in the stem cell filtering process that will be used for the clinical trial.

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Canada launches first gene therapy trial for Fabry disease

Public release date: 21-Jan-2013 [ | E-mail | Share ]

Contact: Katie Delach katie.delach@uphs.upenn.edu 215-349-5964 University of Pennsylvania School of Medicine

PHILADELPHIA - Independent clinical trials, including one conducted at the Scheie Eye Institute at the Perelman School of Medicine, have reported safety and efficacy for Leber congenital amaurosis (LCA), a congenital form of blindness caused by mutations in a gene (RPE65) required for recycling vitamin A in the retina. Inherited retinal degenerative diseases were previously considered untreatable and incurable. There were early improvements in vision observed in the trials, but a key question about the long-term efficacy of gene therapy for curing the retinal degeneration in LCA has remained unanswered. Now, new research from the Scheie Eye Institute, published this week in the Proceedings of the National Academy of Sciences, finds that gene therapy for LCA shows enduring improvement in vision but also advancing degeneration of affected retinal cells, both in LCA patients and animal models of the same condition.

LCA disease from RPE65 mutations has two-components: a biochemical blockade leading to impaired vision, and a progressive loss of the light-sensing photoreceptor cells throughout life of the affected patient. The authors of the new study explain that until now gene therapy has been optimistically assumed, but not proven, to solve both disease components at the same time.

"We all hoped that the gene injections cured both components re-establishing the cycle of vision and also preventing further loss of cells to the second disease component" said Artur V. Cideciyan, PhD, lead author and co-investigator of an LCA clinical trial at Penn.

Yet, when the otherwise invisible cell layers of the retina were measured by optical imaging in clinical trial participants serially over many years, the rate of cell loss was the same in treated and untreated regions. "In other words, gene therapy improved vision but did not slow or halt the progression of cell loss," commented Cideciyan.

"These unexpected observations should help to advance the current treatment by making it better and longer lasting," commented co-author Samuel G. Jacobson, MD, PhD, principal investigator of the clinical trial. "Slowing cell loss in different retinal degenerations has been a major research direction long before the current gene therapy trials. Now, the two directions must converge to ensure the longevity of the beneficial visual effects in this form of LCA."

In a continuation of the longstanding collaboration between the Scheie investigators and the Section of Ophthalmology at Penn School of Veterinary Medicine headed by co-authors Gustavo D. Aguirre, VMD, PhD, and William A. Beltran, DVM, PhD, studies were performed to test whether the clinical results were also present in the canine model of this LCA at disease stages equivalent to those in human patients. "Our gene treatment in this canine model provided the groundwork for the clinical trials of patients, and now we added data to confirm the fact that retinal degeneration does continue despite improved vision" said Aguirre. "The next step is to perform the relevant experiments to ask what intervention will stop the degeneration if added to the gene therapy."

"These new findings contribute to greater clarity in understanding the natural history and complexity of the RPE65 form of LCA and provide a firm foundation for future investigations," said Joan M. O'Brien MD, professor and chair of the Department of Ophthalmology and director of the Scheie Eye Institute.

###

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Penn study sheds light on the complexity of gene therapy for congenital blindness

NEWARK, Calif., Jan. 23, 2013 (GLOBE NEWSWIRE) -- StemCells, Inc. (STEM) announced today that Ann Tsukamoto, Ph.D., Executive Vice President, Research and Development, will make a presentation on the Company's clinical development programs at the Phacilitate Cell & Gene Therapy Forum to be held January 28-30, in Washington, DC. Dr. Tsukamoto is scheduled to speak at 12:25 p.m. ET on Wednesday, January 30, as part of the session on "Clinical development updates from leading cell and gene therapy product candidates in the clinic for CNS indications."

The Phacilitate Cell & Gene Therapy Forum is a preeminent industry-led meeting designed to help advance regulatory, manufacturing, R&D and commercial strategies and drive cell and gene therapy products forward. The Forum enables executives from global cell therapy, gene therapy and tissue engineering companies, representatives of big pharma and big biotech, regulators and regulatory experts, and public and private investors to meet and share information on the leading edge of the regenerative medicine sector.

About StemCells, Inc.

StemCells, Inc. is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The Company's lead therapeutic product candidate, HuCNS-SC(R) cells (purified human neural stem cells), is currently in development as a potential treatment for a broad range of central nervous system disorders. In a Phase I clinical trial in Pelizaeus-Merzbacher disease (PMD), a fatal myelination disorder in children, the Company has shown preliminary evidence of progressive and durable donor-derived myelination in all four patients transplanted with HuCNS-SC cells. The Company is conducting a Phase I/II clinical trial in chronic spinal cord injury in Switzerland and recently reported positive interim data for the first patient cohort. The Company is also conducting a Phase I/II clinical trial in dry age-related macular degeneration (AMD), and is pursuing preclinical studies in Alzheimer's disease. StemCells also markets stem cell research products, including media and reagents, under the SC Proven(R) brand. Further information about StemCells is available at http://www.stemcellsinc.com.

The StemCells, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=7014

Apart from statements of historical fact, the text of this press release constitutes forward-looking statements within the meaning of the U.S. securities laws, and is subject to the safe harbors created therein. These statements include, but are not limited to, statements regarding the clinical development of its HuCNS-SC cells; the Company's ability to commercialize drug discovery and drug development tools; and the future business operations of the Company. These forward-looking statements speak only as of the date of this news release. The Company does not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Such statements reflect management's current views and are based on certain assumptions that may or may not ultimately prove valid. The Company's actual results may vary materially from those contemplated in such forward-looking statements due to risks and uncertainties to which the Company is subject, including those described under the heading "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2011 and in its subsequent reports on Forms 10-Q and 8-K.

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StemCells, Inc. to Present at Phacilitate Cell & Gene Therapy Forum

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/rwzqrh/gene_therapy) has announced the addition of Jain PharmaBiotech's new report "Gene Therapy - Technologies, Markets and Companies" to their offering.

Gene therapy can be broadly defined as the transfer of defined genetic material to specific target cells of a patient for the ultimate purpose of preventing or altering a particular disease state. Genes and DNA are now being introduced without the use of vectors and various techniques are being used to modify the function of genes in vivo without gene transfer. If one adds to this the cell therapy particularly with use of genetically modified cells, the scope of gene therapy becomes much broader. Gene therapy can now combined with antisense techniques such as RNA interference (RNAi), further increasing the therapeutic applications. This report takes broad overview of gene therapy and is the most up-to-date presentation from the author on this topic built-up from a series of gene therapy report written by him during the past decade including a textbook of gene therapy and a book on gene therapy companies. This report describes the setbacks of gene therapy and renewed interest in the topic

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2012-2022. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright.The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

The voluminous literature on gene therapy was reviewed and selected 710 references are appended in the bibliography.The references are constantly updated. The text is supplemented with 72 tables and 15 figures.

Profiles of 178 companies involved in developing gene therapy are presented along with 199 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's web site. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.

Benefits of this report

- Up-to-date on-stop information on gene therapy with 72 tables and 14 figures

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Research and Markets: Gene Therapy - Technologies, Markets and Companies - 2013 Report

Jan. 21, 2013 Independent clinical trials, including one conducted at the Scheie Eye Institute at the Perelman School of Medicine, have reported safety and efficacy for Leber congenital amaurosis (LCA), a congenital form of blindness caused by mutations in a gene (RPE65) required for recycling vitamin A in the retina. Inherited retinal degenerative diseases were previously considered untreatable and incurable. There were early improvements in vision observed in the trials, but a key question about the long-term efficacy of gene therapy for curing the retinal degeneration in LCA has remained unanswered.

Now, new research from the Scheie Eye Institute, published this week in the Proceedings of the National Academy of Sciences, finds that gene therapy for LCA shows enduring improvement in vision but also advancing degeneration of affected retinal cells, both in LCA patients and animal models of the same condition.

LCA disease from RPE65 mutations has two-components: a biochemical blockade leading to impaired vision, and a progressive loss of the light-sensing photoreceptor cells throughout life of the affected patient. The authors of the new study explain that until now gene therapy has been optimistically assumed, but not proven, to solve both disease components at the same time.

"We all hoped that the gene injections cured both components -- re-establishing the cycle of vision and also preventing further loss of cells to the second disease component" said Artur V. Cideciyan, PhD, lead author and co-investigator of an LCA clinical trial at Penn.

Yet, when the otherwise invisible cell layers of the retina were measured by optical imaging in clinical trial participants serially over many years, the rate of cell loss was the same in treated and untreated regions. "In other words, gene therapy improved vision but did not slow or halt the progression of cell loss," commented Cideciyan.

"These unexpected observations should help to advance the current treatment by making it better and longer lasting," commented co-author Samuel G. Jacobson, MD, PhD, principal investigator of the clinical trial. "Slowing cell loss in different retinal degenerations has been a major research direction long before the current gene therapy trials. Now, the two directions must converge to ensure the longevity of the beneficial visual effects in this form of LCA."

In a continuation of the longstanding collaboration between the Scheie investigators and the Section of Ophthalmology at Penn School of Veterinary Medicine headed by co-authors Gustavo D. Aguirre, VMD, PhD, and William A. Beltran, DVM, PhD, studies were performed to test whether the clinical results were also present in the canine model of this LCA at disease stages equivalent to those in human patients.

"Our gene treatment in this canine model provided the groundwork for the clinical trials of patients, and now we added data to confirm the fact that retinal degeneration does continue despite improved vision" said Aguirre. "The next step is to perform the relevant experiments to ask what intervention will stop the degeneration if added to the gene therapy."

"These new findings contribute to greater clarity in understanding the natural history and complexity of the RPE65 form of LCA and provide a firm foundation for future investigations," said Joan M. O'Brien MD, professor and chair of the Department of Ophthalmology and director of the Scheie Eye Institute.

Co-authors, in addition to the Penn researchers include, William W. Hauswirth, PhD, professor of Ophthalmology, at the University of Florida, Gainesville.

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Light shed on complexity of gene therapy for congenital blindness

New Discoveries Provide a Path to a More Complete Cure with Gene Therapy Treatment

Newswise PHILADELPHIA - Independent clinical trials, including one conducted at the Scheie Eye Institute at the Perelman School of Medicine, have reported safety and efficacy for Leber congenital amaurosis (LCA), a congenital form of blindness caused by mutations in a gene (RPE65) required for recycling vitamin A in the retina. Inherited retinal degenerative diseases were previously considered untreatable and incurable. There were early improvements in vision observed in the trials, but a key question about the long-term efficacy of gene therapy for curing the retinal degeneration in LCA has remained unanswered. Now, new research from the Scheie Eye Institute, published this week in the Proceedings of the National Academy of Sciences, finds that gene therapy for LCA shows enduring improvement in vision but also advancing degeneration of affected retinal cells, both in LCA patients and animal models of the same condition.

LCA disease from RPE65 mutations has two-components: a biochemical blockade leading to impaired vision, and a progressive loss of the light-sensing photoreceptor cells throughout life of the affected patient. The authors of the new study explain that until now gene therapy has been optimistically assumed, but not proven, to solve both disease components at the same time.

We all hoped that the gene injections cured both components re-establishing the cycle of vision and also preventing further loss of cells to the second disease component said Artur V. Cideciyan, PhD, lead author and co-investigator of an LCA clinical trial at Penn.

Yet, when the otherwise invisible cell layers of the retina were measured by optical imaging in clinical trial participants serially over many years, the rate of cell loss was the same in treated and untreated regions. In other words, gene therapy improved vision but did not slow or halt the progression of cell loss, commented Cideciyan.

These unexpected observations should help to advance the current treatment by making it better and longer lasting, commented co-author Samuel G. Jacobson, MD, PhD, principal investigator of the clinical trial. Slowing cell loss in different retinal degenerations has been a major research direction long before the current gene therapy trials. Now, the two directions must converge to ensure the longevity of the beneficial visual effects in this form of LCA.

In a continuation of the longstanding collaboration between the Scheie investigators and the Section of Ophthalmology at Penn School of Veterinary Medicine headed by co-authors Gustavo D. Aguirre, VMD, PhD, and William A. Beltran, DVM, PhD, studies were performed to test whether the clinical results were also present in the canine model of this LCA at disease stages equivalent to those in human patients.

Our gene treatment in this canine model provided the groundwork for the clinical trials of patients, and now we added data to confirm the fact that retinal degeneration does continue despite improved vision said Aguirre. The next step is to perform the relevant experiments to ask what intervention will stop the degeneration if added to the gene therapy.

These new findings contribute to greater clarity in understanding the natural history and complexity of the RPE65 form of LCA and provide a firm foundation for future investigations, said Joan M. OBrien MD, professor and chair of the Department of Ophthalmology and director of the Scheie Eye Institute.

Co-authors, in addition to the Penn researchers include, William W. Hauswirth, PhD, professor of Ophthalmology, at the University of Florida, Gainesville.

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Study Sheds Light on the Complexity of Gene Therapy for Congenital Blindness

Washington, January 16 (ANI): In a preliminary study in a canine model of Duchenne muscular dystrophy (DMD), researchers have shown a giant leap using gene therapy to treat muscular dystrophy.

Muscular dystrophy occurs when damaged muscle tissue is replaced with fibrous, bony or fatty tissue and loses function. Duchenne muscular dystrophy is the most common type of muscular dystrophy predominantly affecting boys.

Patients with DMD have a gene mutation that disrupts the production of dystrophin, a protein essential for muscle cell survival and function. Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death.

For years, scientists have been working to find the key to restoring dystrophin, but they have faced many challenges.

One of the largest hurdles in DMD gene therapy is the large size of the gene. Dystrophin is the largest gene in the human genome, containing approximately 4,000 amino acids.

To fit the dystrophin gene into a vehicle that could deliver the gene to the appropriate site in the body, one has to delete 70 percent of the gene. The highly abbreviated gene is known as the "micro-dystrophin" gene.

Previous studies suggest that micro-dystrophin can effectively stop muscle disease in mice that are missing dystrophin. However, mice that are missing dystrophin show minimal DMD symptoms, and results from mice often do not predict what will happen in humans.

In contrast to mice, loss of dystrophin results in severe muscular dystrophy in dogs. If micro-dystrophin can work in dystrophic dogs, it will likely work in human patients. Unfortunately, when micro-dystrophin was tested in dogs in previous studies, it was not successful.

To overcome these hurdles, a team led by Dongsheng Duan, the Margaret Proctor Mulligan Professor in Medical Research at the University of Missouri School of Medicine, engineered a new micro-dystrophin gene that carries an important functional region missing in previously tested micro-dystrophins.

"We placed the new microgene into a virus and then injected the virus into dystrophic dogs' muscles," Duan said.

Continued here:

Experts take quantum leap in gene therapy to treat muscular dystrophy

Jan. 15, 2013 Usually, results from a new study help scientists inch their way toward an answer whether they are battling a health problem or are on the verge of a technological breakthrough. Once in a while, those results give them a giant leap forward. In a preliminary study in a canine model of Duchenne muscular dystrophy (DMD), University of Missouri scientists showed exactly such a leap using gene therapy to treat muscular dystrophy.

The results of the study will be published in the journal Molecular Therapy on Jan. 15, 2013.

Muscular dystrophy occurs when damaged muscle tissue is replaced with fibrous, bony or fatty tissue and loses function. Duchenne muscular dystrophy is the most common type of muscular dystrophy predominantly affecting boys. Patients with DMD have a gene mutation that disrupts the production of dystrophin, a protein essential for muscle cell survival and function. Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death. For years, scientists have been working to find the key to restoring dystrophin, but they have faced many challenges.

One of the largest hurdles in DMD gene therapy is the large size of the gene. Dystrophin is the largest gene in the human genome, containing approximately 4,000 amino acids. To fit the dystrophin gene into a vehicle that could deliver the gene to the appropriate site in the body, one has to delete 70 percent of the gene. The highly abbreviated gene is known as the "micro-dystrophin" gene. Previous studies suggest that micro-dystrophin can effectively stop muscle disease in mice that are missing dystrophin. However, mice that are missing dystrophin show minimal DMD symptoms, and results from mice often do not predict what will happen in humans. In contrast to mice, loss of dystrophin results in severe muscular dystrophy in dogs. If micro-dystrophin can work in dystrophic dogs, it will likely work in human patients. Unfortunately, when micro-dystrophin was tested in dogs in previous studies, it was not successful.

To overcome these hurdles, a team led by Dongsheng Duan, the Margaret Proctor Mulligan Professor in Medical Research at the MU School of Medicine, engineered a new micro-dystrophin gene that carries an important functional region missing in previously tested micro-dystrophins.

"We placed the new microgene into a virus and then injected the virus into dystrophic dogs' muscles," Duan said. Following gene therapy, Duan's team examined the dogs for signs of muscle disease and measured muscle force in treated and untreated dogs. After careful evaluation of 22 dogs, Duan and colleagues found that the new version of micro-dystrophin not only reduced inflammation and fibrosis, it also effectively improved muscle strength.

"This is the first time that we have seen positive gene therapy results in large mammals of DMD," said Duan. "We still have a lot of work to do, but we now know that our gene therapy strategy works in large mammals; this is a quantum leap forward in fighting this disease. Our next step is to test our strategy in a large group of muscles in the dogs, and then, eventually, see if 'whole body therapy' will work in the dogs. We are still a long way off before we will have a human treatment, but with this finding, I do see a light at the end of this tunnel."

If additional studies, including animal studies, are successful within the next few years, MU officials would request authority from the federal government to begin human drug development (this is commonly referred to as the "investigative new drug" status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for Duchenne muscular dystrophy.

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Quantum leap in gene therapy of Duchenne muscular dystrophy

gene therapy strategies to offensive biowarfare
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gene therapy strategies to offensive biowarfare - Video

Annual Review 2012 - Gene Therapy Trial for Blindness

By: oxford

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Annual Review 2012 - Gene Therapy Trial for Blindness - Video

January 5, 2013

redOrbit Staff & Wire Reports Your Universe Online

A team of US researchers has reportedly developed a way to reprogram scar tissue from damaged hearts into healthy muscle through gene therapy a discovery which could help strengthen hearts harmed as a result of cardiovascular events.

According to a recent statement, scientists from Weill Cornell Medical College, along with colleagues from the Baylor College of Medicine (BCM) and Stony Brook University Medical Center have discovered a combination of three specific genes can turn cells in the scar tissue into fully-functioning muscle cells, and the addition of a fourth can stimulate blood vessel growth and make the process even more effective.

Typically, the hearts blood supply is cut off during a heart attack, causing muscles to die off and become scarred, the researchers explained. The result is a weakened heart which will eventually lead to heart failure for those who have experienced serious cardiovascular events. This, however, could be avoided if medical experts could find a way to transform scar tissue into normal heart tissue, thus strengthening the heart as a whole.

To that end, Dr. Todd K. Rosengart, chair at BCMs Michael E. DeBakey Department of Surgery, and colleagues implanted either three forms of a gene that encourages blood vessel growth known as the vascular endothelial growth factor (VEGF) gene or an inactive material into the hearts of rats.

Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein), the researchers explained. The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT.

The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart), they added. The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.

The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting, Dr. Rosengart, the corresponding author of the study, said. The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene.

This experiment is a proof of principle. Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts, added Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College. We have shown both that GMT can effect change that enhances the activity of the heart and that the VEGF gene is effective in improving heart function even more.

Original post:

Damaged Heart Strengthened Using New Gene Therapy Method

Disease is on the run! An incredible advance in the realm of gene therapy has been made by top researchers in the US and Sweden. A single enzyme from a bacterias immune system can effectively be used to locate specific sections of DNA in a living cell. From there, entire genes can be neutralized or replaced with superior sections of DNA. Clearly, we are on the brink of gene therapy becoming a common and highly effective treatment for terrible diseases like AIDS and cancer.

A group of researchers from MIT, the Broad Institute, and Rockefeller University have been able to use bacterial protein-RNA systems to find and disrupt the DNA of a virus. Cas9, an enzyme that can break the bond in nucleotide subunits of the nucleic acids, is used to target specific parts of a genome. When it finds a match, the Cas9 effectively cuts that segment of DNA. From there, it either leaves the gene non-functional, or allows the researchers to insert replacement DNA into the genome. Impressively, this method is highly precise. Unlike previous attempts at snipping out chunks of DNA, this method will only activate if the DNA segment is an exact match.

Meanwhile, researchers at the Howard Hughes Medical Institute, UC Berkeley, and Emmanuelle Charpentier of the Laboratory for Molecular Infection Medicine have published two papers in Science Express explaining their research on the Cas9enzyme. Harvard Professor George Church explains that Cas9 is five times more efficient than the TALEN (Transcription Activator-Like Effector Nucleases) method of gene alteration. While the TALEN and zinc-finger nucleases techniques are useful, they require much more work and are less precise than Cas9. This new method needs only a tiny RNA molecule to be programmed to seek a specific section of DNA.

Once we pinpoint specific genes that cause a disease, Cas9 can be sent in to remove the offending base pairs. Clinical trials using the zinc-finger nucleases method are being performed already, and this breakthrough will provide even more options going forward. Feng Zhang, an MIT assistant professor, believes that this can even be used to study disease by causing mutations in healthy cells. Previously fatal diseases can now be targeted and even potentially cured. Correcting defective genes and stomping out rogue viruses are on the table now, and its only a matter of time before gene therapy becomes a common tool like vaccines and antibiotics for physicians.

Now read: Harvard cracks DNA storage, crams 700 terabytes of data into a single gram

Research papers:DOI:10.1126/science.1232033 RNA-Guided Human Genome Engineering via Cas9; DOI: 10.1126/science.1231143 Multiplex Genome Engineering Using CRISPR/Cas Systems; RNA-programmed genome editing in human cells [PDF]

[Image credit: Duncan Hull & Stuart Caie]

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MIT researchers crack cheap, precise gene therapy

Whole-genome Testing and the Possibility of Gene Therapy for Neurological Disorders
(Visit: http://www.uctv.tv Soon everyone can have their genome sequenced. Will this information improve health, or simply clarify our fate? Series: "MIND Institute Lecture Series on Neurodevelopmental Disorders" [Health and Medicine] [Show ID: 24540]

By: UCtelevision

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Whole-genome Testing and the Possibility of Gene Therapy for Neurological Disorders - Video

PORT ST. LUCIE, Fla.--(BUSINESS WIRE)--

The Vaccine & Gene Therapy Institute of Florida (VGTI Florida), a leading nonprofit immunological research institute, is pleased to announce the appointment of Keith Knutson, Ph.D., Program Director. Dr. Knutson will be joining VGTI Florida along with several members of his lab. His work will focus on immunotherapeutic approaches in breast and ovarian cancers and how vaccines can boost immunity and help the bodys defense system fight off these cancers.

Dr. Knutson recently received a $3.7 million grant from the National Cancer Institute (NCI) to identify immunologic biomarkers or proteins that could be useful in identifying breast cancer patients who are unlikely to respond to certain therapies. This can help to determine whether a drug used in specific patient groups can be effective or whether these patients should be treated with a different therapeutic regimen.

Cancer is an important area of research focus for VGTI Florida, and Dr. Knutsons work will help make great strides in the understanding and treatment of breast and ovarian cancers, said Jay Nelson, Ph.D., founder and Executive Director of the institute. Dr. Knutson is a leader in his field and we welcome his expertise in treating two serious diseases that affect so many millions of women around the world, said Rafick Pierre Skaly, Ph.D., Chief Scientific Officer and Co-Director of VGTI Florida.

Dr. Knutson is currently the Director of the Ovarian Cancer Immunology and Immunotherapy Program at the Mayo Clinic, Rochester, Minnesota and is also a Member of the U.S. Department of Defenses Breast Cancer Research Program Integration Panel, the primary body that makes decisions on funding. He is the Co-Director of the Mayo Clinic Immune Monitoring Core which is engaged in providing a variety of different immune monitoring and phenotyping services for research purposes across a variety of scientific disciplines including tumor immunology, rheumatoid arthritis, and infectious diseases.

Dr. Knutson has co-authored numerous articles in scientific journals including The Journal of Immunology; The American Journal of Pathology; Cancer Immunology, Immunotherapy and many others. He has a Bachelor of Science in Microbiology from the University of Washington and earned a Ph.D. in pharmacology from the University of Georgia. He completed two postdoctoral fellowships, one in the Division of Medical Oncology, University of Washington and another at the Department of Medicine, University of British Columbia. Following postdoctoral training, Dr. Knutson was awarded the Howard Temin Award from the National Cancer Institute.

VGTI Florida

VGTI Florida is a leading immunological research institute that is on an urgent mission to transform scientific discoveries into novel treatments and cures for devastating chronic illnesses such as cancer and HIV/AIDS, and infectious diseases. VGTI Florida is an independent non-profit 501(c)(3) organization located in the Tradition Center for Innovation in Port St. Lucie, Florida. For more information, please visit http://www.VGTIFL.org.

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Dr. Keith Knutson Joins the Vaccine & Gene Therapy Institute of Florida as A Research Program Director in Oncology

Public release date: 4-Jan-2013 [ | E-mail | Share ]

Contact: Lauren Woods Law2014@med.cornell.edu 646-317-7401 Weill Cornell Medical College

NEW YORK (Jan. 4, 2013) -- A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association.

"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author. "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."

"This experiment is a proof of principle," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein.)

The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.)

The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.

Rosengart emphasizes that more work needs to be completed to show that the effect of the VEGF is real, but it has real promise as part of a new treatment for heart attack that would minimize heart damage.

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Gene therapy reprograms scar tissue in damaged hearts into healthy heart muscle

Written by Kait Shea, Assistant Editor Friday, 04 January 2013 11:00

There may not be a cure for cancer just yet, but the Alliance for Cancer Gene Therapy (ACGT), a nonprofit established by a Greenwich couple thats dedicated to gene therapy, is making big strides in treatment.

The Stamford-based organization is the only nonprofit in the United States dedicated exclusively to cell and gene cancer therapy research. One hundred percent of all contributions to ACGT go directly to research and fund grants with leading scientists in the country, representing 28 prestigious medical institutions. Many feel that because of this ACGT has played a major role in what many doctors believe may be the key to healing those plagued by the disease.

In an interview with the Post, Ms. Netter said she and her late husband realized this really is a key to perhaps finding the answers to cancer and immediately sought to put their energies and resources into it on hope and faith. After a year of fund raising, the couple officially embarked on their mission to provide grants to the nations leading scientific investigators for cancer gene therapy research.

With the help of ACGTs Scientific Advisory Council, a group composed of leading scientists and doctors who conduct rigorous reviews of grants to ensure that the most promising cancer gene therapy projects are given funding, the Netters awarded more than $22 million in grants within the first 10 years of launching their organization.

The latest strides in gene therapy projects funded by ACGT, however, are the most exciting the organization has seen, Ms. Netter said. The alliance played a significant part in the recent leukemia study pioneered by scientists at the Perelman School of Medicine at the University of Pennsylvania. ACGT provided the initial funds for the study, which has found success using immune-mediated gene therapy for leukemia and lymphoma.

According to Ms. Netter, the therapy used involves removing immune cells from the body of the patient, bioengineering and strengthening them, then reinfusing them into the patient using a gutted out HIV vector, which reprograms the patients immune system genetically to kill cancer. The T cells directly target and kill cancer cells and circulate through the body for at least a few years, and Ms. Netter called it an enormous breakthrough.

Initial ACGT grants for the immune mediated gene therapy project were awarded in 2004 to Carl June of the Abramson Family Cancer Research Institute at the University of Pennsylvania and to Michel Sadelain, of Memorial Sloan-Kettering Cancer Center, Gene Therapy and Gene Expression Laboratory, in New York City. Preliminary results were issued by Dr. June in August 2011, with additional results released in December 2012, delivering some of the most promising results seen to date in the search for a cure.

The clinical trial participants, all of whom had advanced cancers, included 10 adult patients with chronic lymphocytic leukemia who were treated at the Hospital of the University of Pennsylvania and two children with acute lymphoblastic leukemia who were treated at the Childrens Hospital of Philadelphia. Two of the first three adult patients treated with the protocol remained healthy and in full remission more than two years after their treatment, with the engineered cells still circulating in their bodies. Currently, nine out of the 12 participants show their disease in remission.

Perhaps the most amazing story of recovery, Ms. Netter said, was that of now 7-year-old Emma Whitehead, who was on the brink of death, suffering from acute lymphoblastic leukemia. After trying traditional cancer treatments like chemotherapy without any improvement, Emmas parents decided to try the experimental T-cell therapy. And although the treatment nearly killed Emma, her health rapidly improved and she emerged cancer-free, Ms. Netter said. The young girl is now out of the hospital and leading the life of a regular second grader, with eight months of remission from the disease under her belt.

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Gene therapy: Local group seeks ‘answers to cancer’