Category Archives: Gene therapy

From Nature magazine

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One day in early 1995 a man named bob massie walked into my office at the outpatient clinic of Massachusetts General Hospital in Boston. Massie told me he had been infected with HIV--the virus that causes AIDS--for 16 years and yet had never shown any symptoms. My physical examination confirmed he was healthy, in stark contrast to all other patients I saw that day. At that time, a new combination of drugs was being tested that would eventually slow the progressive decline in immune function that HIV caused. In 1995, however, most people who had been infected with HIV for a decade or more had already progressed to AIDS--the stage marked by the inability to fight off other pathogens. The young man standing before me had never taken anti-HIV medication and strongly believed that if I learned the secret to his good fortune, the information could help others to survive what was then generally thought to be a uniformly fatal disease.

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Tears and a runny nose can be unpleasant on a windy day, but these mucosal secretions play a vital role in protecting the body from viruses and other malicious microbes. Unfortunately, mucus is also adept at washing away medication designed to treat infections and inflammation that occur when an infectious agent is successful in penetrating the body's defenses [More]

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DUBLIN--(BUSINESS WIRE)--

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

Gene Therapy: the Next Big Step in Cancer Treatments.

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

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

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

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

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

Companies Mentioned

- ReGenX Biosciences

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

Public release date: 6-Jul-2012 [ | E-mail | Share ]

Contact: Dr. Changfa Guo guo.changfa@zs-hospital.sh.cn Society for Experimental Biology and Medicine

Dr Changfa Guo, Professor Chunsheng Wang and their co-investigators from Zhongshan hospital Fudan University, Shanghai, China have established a novel hyperbranched poly(amidoamine) (hPAMAM) nanoparticle based hypoxia regulated vascular endothelial growth factor (HRE-VEGF) gene therapy strategy which is an excellent substitute for the current expensive and uncontrollable VEGF gene delivery system. This discovery, reported in the June 2012 issue of Experimental Biology and Medicine, provides an economical, feasible and biocompatible gene therapy strategy for cardiac repair.

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

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

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

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

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

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Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.rsmjournals.com/

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

Public release date: 6-Jul-2012 [ | E-mail | Share ]

Contact: Dr. Changfa Guo guo.changfa@zs-hospital.sh.cn Society for Experimental Biology and Medicine

Dr Changfa Guo, Professor Chunsheng Wang and their co-investigators from Zhongshan hospital Fudan University, Shanghai, China have established a novel hyperbranched poly(amidoamine) (hPAMAM) nanoparticle based hypoxia regulated vascular endothelial growth factor (HRE-VEGF) gene therapy strategy which is an excellent substitute for the current expensive and uncontrollable VEGF gene delivery system. This discovery, reported in the June 2012 issue of Experimental Biology and Medicine, provides an economical, feasible and biocompatible gene therapy strategy for cardiac repair.

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

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

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

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

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

###

Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.rsmjournals.com/

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

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

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

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

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

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

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About the Journal

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

About the Publisher

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

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Targeted gene therapy enhances treatment for Pompe disease

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

bluebird bio, a leader in the development of innovative gene therapies for severe genetic disorders, announced today that both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted an orphan drug designation to its investigational gene therapy product for the treatment of adrenoleukodystrophy (ALD). The product consists of the patients own CD34+ hematopoietic stem cells transduced with bluebird bios lentiviral vector, Lenti-D, encoding the human ABCD1 cDNA. Based on promising early clinical proof of concept results, bluebird bio plans to initiate a Phase 2/3 clinical study in childhood cerebral ALD in both the United States and Europe in 2013.

Receiving orphan drug designation is a positive step forward in our efforts to bring hope to ALD patients and their families, said David Davidson, M.D., chief medical officer of bluebird bio. We believe our lentiviral technology has the potential to be a one-time transformative therapy for patients suffering from rare genetic disorders like ALD for whom there are limited treatment options. bluebird is committed to advancing the clinical and commercial development of our gene therapy platform because of the dramatic benefit it may have on the lives of patients.

Orphan drug designation, which is intended to facilitate drug development for rare diseases, provides substantial benefits to the sponsor, including the potential for funding for certain clinical studies, study-design assistance, and several years of market exclusivity for the product upon regulatory approval.

About ALD

Adrenoleukodystrophy (ALD) is a rare X-linked, inherited neurological disorder that, in its most severe form, causes damage to the myelin sheath (an insulating layer of membranes that surrounds nerve cells in the brain) and progressive dysfunction of the adrenal glands. Also known as Lorenzo's Oil disease, ALD is estimated to affect one in every 21,000 boys worldwide. In the childhood cerebral form (CCALD), symptoms usually occur between the ages of 4 and 10. Boys afflicted with this form of ALD develop normally until the onset of symptoms. The symptoms of this disorder often progress rapidly and, in a matter of years, can lead to a vegetative state and, ultimately, death. Current treatment options are limited to allogeneic stem cell transplantation when there is an appropriate donor. Allogeneic transplants carry a significant risk of serious morbidity and death.

About bluebird bio's CCALD Product Development

bluebird bios CCALD product program has the potential to halt the progression of CCALD by providing a functional ABCD1 gene to the patients own stem cells. These stem cells proliferate, and some of the progeny cells travel to the brain where they become microglial cells incorporating the corrective gene. Data from the first clinical study treating X-linked CCALD patients with the companys lentiviral gene therapy product demonstrated continued stable expression of the transgene and the corresponding ABCD-1 protein for over four years in two CCALD patients, resulting in prolonged disease stabilization. bluebird bio plans to initiate a Phase 2/3 clinical study in CCALD in both the United States and Europe in 2013.

About bluebird bio

bluebird bio is developing innovative gene therapies for severe genetic disorders. At the heart of bluebird bios product creation efforts is its broadly applicable gene therapy platform for the development of novel treatments for diseases with few or no clinical options. The companys novel approach uses stem cells harvested from the patients own bone marrow into which a healthy version of the disease causing gene is inserted. bluebird bios approach represents a true paradigm shift in the treatment of severe genetic diseases by eliminating the potential complications associated with donor cell transplantation and presenting a one-time potentially transformative therapy using a patients own stem cells. bluebird bio has two later stage clinical products in development for childhood cerebral adrenoleukodystrophy (CCALD) and beta-thalassemia/sickle cell anemia. Led by a world-class team, bluebird bio is privately held and backed by top-tier life sciences investors, including Third Rock Ventures, TVM Capital, ARCH Venture Partners, Forbion Capital Partners, Easton Capital and Genzyme Ventures. Its operations are located in Cambridge, Mass. and Paris, France. For more information, please visit http://www.bluebirdbio.com.

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bluebird bio Receives U.S. and European Orphan Drug Designation for Novel Gene Therapy to Treat Adrenoleukodystrophy

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

bluebird bio, a leader in the development of innovative gene therapies for severe genetic disorders, announced today that both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted an orphan drug designation to its investigational gene therapy product for the treatment of adrenoleukodystrophy (ALD). The product consists of the patients own CD34+ hematopoietic stem cells transduced with bluebird bios lentiviral vector, Lenti-D, encoding the human ABCD1 cDNA. Based on promising early clinical proof of concept results, bluebird bio plans to initiate a Phase 2/3 clinical study in childhood cerebral ALD in both the United States and Europe in 2013.

Receiving orphan drug designation is a positive step forward in our efforts to bring hope to ALD patients and their families, said David Davidson, M.D., chief medical officer of bluebird bio. We believe our lentiviral technology has the potential to be a one-time transformative therapy for patients suffering from rare genetic disorders like ALD for whom there are limited treatment options. bluebird is committed to advancing the clinical and commercial development of our gene therapy platform because of the dramatic benefit it may have on the lives of patients.

Orphan drug designation, which is intended to facilitate drug development for rare diseases, provides substantial benefits to the sponsor, including the potential for funding for certain clinical studies, study-design assistance, and several years of market exclusivity for the product upon regulatory approval.

About ALD

Adrenoleukodystrophy (ALD) is a rare X-linked, inherited neurological disorder that, in its most severe form, causes damage to the myelin sheath (an insulating layer of membranes that surrounds nerve cells in the brain) and progressive dysfunction of the adrenal glands. Also known as Lorenzo's Oil disease, ALD is estimated to affect one in every 21,000 boys worldwide. In the childhood cerebral form (CCALD), symptoms usually occur between the ages of 4 and 10. Boys afflicted with this form of ALD develop normally until the onset of symptoms. The symptoms of this disorder often progress rapidly and, in a matter of years, can lead to a vegetative state and, ultimately, death. Current treatment options are limited to allogeneic stem cell transplantation when there is an appropriate donor. Allogeneic transplants carry a significant risk of serious morbidity and death.

About bluebird bio's CCALD Product Development

bluebird bios CCALD product program has the potential to halt the progression of CCALD by providing a functional ABCD1 gene to the patients own stem cells. These stem cells proliferate, and some of the progeny cells travel to the brain where they become microglial cells incorporating the corrective gene. Data from the first clinical study treating X-linked CCALD patients with the companys lentiviral gene therapy product demonstrated continued stable expression of the transgene and the corresponding ABCD-1 protein for over four years in two CCALD patients, resulting in prolonged disease stabilization. bluebird bio plans to initiate a Phase 2/3 clinical study in CCALD in both the United States and Europe in 2013.

About bluebird bio

bluebird bio is developing innovative gene therapies for severe genetic disorders. At the heart of bluebird bios product creation efforts is its broadly applicable gene therapy platform for the development of novel treatments for diseases with few or no clinical options. The companys novel approach uses stem cells harvested from the patients own bone marrow into which a healthy version of the disease causing gene is inserted. bluebird bios approach represents a true paradigm shift in the treatment of severe genetic diseases by eliminating the potential complications associated with donor cell transplantation and presenting a one-time potentially transformative therapy using a patients own stem cells. bluebird bio has two later stage clinical products in development for childhood cerebral adrenoleukodystrophy (CCALD) and beta-thalassemia/sickle cell anemia. Led by a world-class team, bluebird bio is privately held and backed by top-tier life sciences investors, including Third Rock Ventures, TVM Capital, ARCH Venture Partners, Forbion Capital Partners, Easton Capital and Genzyme Ventures. Its operations are located in Cambridge, Mass. and Paris, France. For more information, please visit http://www.bluebirdbio.com.

Read the original here:
bluebird bio Receives U.S. and European Orphan Drug Designation for Novel Gene Therapy to Treat Adrenoleukodystrophy

Public release date: 18-Jun-2012 [ | E-mail | Share ]

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

New Rochelle, NY, June 18, 2012A single-dose vaccine capable of providing immunity against the effects of cocaine offers a novel and groundbreaking strategy for treating cocaine addiction is described in an article published Instant Online in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc. (http://www.liebertpub.com) The article is available free online at the Human Gene Therapy website (http://www.liebertpub.com/hum).

"This is a very novel approach for addressing the huge medical problem of cocaine addiction," says James M. Wilson, MD, PhD, Editor-in-Chief, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

In the article "AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior," (http://online.liebertpub.com/doi/pdfplus/10.1089/hum.2011.178) a team of researchers from Weill Cornell Medical College (New York, NY), The Scripps Research Institute (La Jolla, CA), and Cornell University (Ithaca, NY) used a virus-based delivery vehicle in mice to transfer a gene that produces a protein capable of binding to cocaine present in the blood, preventing the cocaine from crossing into the brain. The protein is a monoclonal antibody that sequesters cocaine, making the vaccinated mice resistant to the drug's effects. Whereas unvaccinated mice exhibited hyperactivity when exposed to intravenous cocaine, the immunized mice showed no effects, according to authors Jonathan Rosenberg, et al.

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About the Journal

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

About the Publisher

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

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Anti-cocaine vaccine described in Human Gene Therapy Journal