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

Contact: Jim Bernstein jbernstein@aspet.org 301-646-3259 Federation of American Societies for Experimental Biology

BOSTON Researchers at Northeastern University in Boston have developed a gene therapy approach that may one day stop Parkinson's disease (PD) in it tracks, preventing disease progression and reversing its symptoms. The novelty of the approach lies in the nasal route of administration and nanoparticles containing a gene capable of rescuing dying neurons in the brain. Parkinson's is a devastating neurodegenerative disorder caused by the death of dopamine neurons in a key motor area of the brain, the substantia nigra (SN). Loss of these neurons leads to the characteristic tremor and slowed movements of PD, which get increasingly worse with time. Currently, more than 1% of the population over age 60 has PD and approximately 60,000 Americans are newly diagnosed every year. The available drugs on the market for PD mimic or replace the lost dopamine but do not get to the heart of the problem, which is the progressive loss of the dopamine neurons.

The focus of Dr. Barbara Waszczak's lab at Northeastern University in Boston is to find a way to harvest the potential of glial cell line-derived neurotrophic factor (GDNF) as a treatment for PD. GDNF is a protein known to nourish dopamine neurons by activating survival and growth-promoting pathways inside the cells. Not surprisingly, GDNF is able to protect dopamine neurons from injury and restore the function of damaged and dying neurons in many animal models of PD. However, the action of GDNF is limited by its inability to cross the blood-brain barrier (BBB), thus requiring direct surgical injection into the brain. To circumvent this problem, Waszczak's lab is investigating intranasal delivery as a way to bypass the BBB. Their previous work showed that intranasal delivery of GDNF protects dopamine neurons from damage by the neurotoxin, 6-hydroxydopamine (6-OHDA), a standard rat model of PD.

Taking this work a step further, Brendan Harmon, working in Waszczak's lab, has adapted the intranasal approach so that cells in the brain can continuously produce GDNF. His work utilized nanoparticles, developed by Copernicus Therapeutics, Inc., which are able to transfect brain cells with an expression plasmid carrying the gene for GDNF (pGDNF). When given intranasally to rats, these pGDNF nanoparticles increase GDNF production throughout the brain for long periods, avoiding the need for frequent re-dosing. Now, in new research presented on April 20 at 12:30 pm during Experimental Biology 2013 in Boston, MA, Harmon reports that intranasal administration of Copernicus' pGDNF nanoparticles results in GDNF expression sufficient to protect SN dopamine neurons in the 6-OHDA model of PD.

Waszczak and Harmon believe that intranasal delivery of Copernicus' nanoparticles may provide an effective and non-invasive means of GDNF gene therapy for PD, and an avenue for transporting other gene therapy vectors to the brain. This work, which was funded in part by the Michael J. Fox Foundation for Parkinson's Research and Northeastern University, has the potential to greatly expand treatment options for PD and many other central nervous system disorders.

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To request an interview with Dr. Waszczak, please contact Jim Bernstein at the contact information listed above.

About Experimental Biology 2013

Experimental Biology's mission is to share the newest scientific concepts and research findings shaping future and current clinical advances and to give scientists and clinicians an unparalleled opportunity to hear from colleagues working on similar biomedical problems using different disciplines. With six sponsoring societies and another 20 U.S. and international guest societies, the annual meeting brings together scientists from throughout the United States and the world, representing dozens of scientific areas, from laboratory to translational to clinical research. The meeting also offers a wide spectrum of professional development sessions.

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A noninvasive avenue for Parkinson's disease gene therapy

Public release date: 19-Apr-2013 [ | E-mail | Share ]

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

PHILADELPHIA A gene therapy study focused on finding a cure for a rare congenital blinding disease has been recognized as one of the ten most outstanding clinical research projects of the year by the Clinical Research Forum (CRF). The study, led by Jean Bennett, MD, Phd, F.M. Kirby professor of Ophthalmology at the University of Pennsylvania School of Medicine, and carried out in collaboration with Penn Medicine's Albert M. Maguire, MD, and Katherine A. High, MD at The Children's Hospital of Philadelphia (CHOP), has been presented with the Distinguished Clinical Research Achievement Award, the second highest given in the CRF's Annual Top 10 Clinical Research Achievement Awards. CRF award winners are cited as the most compelling examples of scientific innovation that results from the nation's investment in clinical research that can benefit human health and welfare.

The results of the most recent phase of the study for Leber's Congenital Amaurosis (LCA) at CHOP have led to the first Phase 3 gene therapy study in the United States and the first Phase 3 gene therapy study in the world for a non-lethal disorder. The team of researchers hopes that the studies could lead to the first approved gene therapy product in the United States.

"The data from our study has already been used to develop additional clinical trials for other blinding diseases," said Bennett. "There are two things that I think are really going to be important from this work: one, that we'll move forward with this particular disease and get approval for the drug that we've been developing, and two, that this could ultimately lead to approved treatments for other currently untreatable conditions."

Published in 2012, the winning studies are the latest in a long tradition of notable health advances that have occurred through clinical research such as eliminating polio, reducing the mortality of AIDS, and improving cancer survival rates that were propelled by combined investment in basic science and clinical research.

"These patients, once rendered blind by LCA, have had their lives transformed and their vision restored by this team's efforts to further gene therapy research," said Joan O'Brien, MD, chair of the department of Ophthalmology at the Scheie Eye Institute at Penn Medicine. "The groundbreaking work sets the stage for the treatment of numerous other blinding conditions, but is also a shining example of what scientists with NIH resources can accomplish for the betterment of humanity."

###

The Clinical Research Forum is an organization comprised of the nation's most prestigious and acclaimed academic medical centers and healthcare systems whose goal is to sustain and expand a cadre of talented, well-trained clinical investigators at all stage of career development, and support nurturing environments and comprehensive research capabilities within academic institutions. Its mission is to provide leadership to the national clinical and translational research enterprise and promote understanding and support for clinical research and its impact on health.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

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Penn receives prestigious national award for breakthrough in gene therapy

PHILADELPHIA A gene therapy study focused on finding a cure for a rare congenital blinding disease has been recognized as one of the ten most outstanding clinical research projects of the year by the Clinical Research Forum (CRF). The study, led by Jean Bennett, MD, Phd, F.M. Kirby professor ofOphthalmologyat the University of Pennsylvania School of Medicine, and carried out in collaboration with Penn Medicines Albert M. Maguire, MD, and Katherine A. High, MD at The Childrens Hospital of Philadelphia (CHOP), has been presented with the Distinguished Clinical Research Achievement Award, the second highest given in the CRFs Annual Top 10 Clinical Research Achievement Awards. CRF award winners are cited as the most compelling examples of scientific innovation that results from the nations investment in clinical research that can benefit human health and welfare.

The results of the most recent phase of the study for Lebers Congenital Amaurosis (LCA) at CHOP have led to the first Phase 3 gene therapy study in the United States and the first Phase 3 gene therapy study in the world for a non-lethal disorder. The team of researchers hopes that the studies could lead to the first approved gene therapy product in the United States.

The data from our study has already been used to develop additional clinical trials for other blinding diseases, said Bennett. There are two things that I think are really going to be important from this work: one, that well move forward with this particular disease and get approval for the drug that weve been developing, and two, that this could ultimately lead to approved treatments for other currently untreatable conditions.

Published in 2012, the winning studies are the latest in a long tradition of notable health advances that have occurred through clinical research such as eliminating polio, reducing the mortality of AIDS, and improving cancer survival rates that were propelled by combined investment in basic science and clinical research.

These patients, once rendered blind by LCA, have had their lives transformed and their vision restored by this teams efforts to further gene therapy research, said Joan OBrien, MD, chair of the department of Ophthalmology at the Scheie Eye Institute at Penn Medicine. The groundbreaking work sets the stage for the treatment of numerous other blinding conditions, but is also a shining example of what scientists with NIH resources can accomplish for the betterment of humanity.

The Clinical Research Forum is an organization comprised of the nations most prestigious and acclaimed academic medical centers and healthcare systems whose goal is to sustain and expand a cadre of talented, well-trained clinical investigators at all stage of career development, and support nurturing environments and comprehensive research capabilities within academic institutions. Its mission is to provide leadership to the national clinical and translational research enterprise and promote understanding and support for clinical research and its impact on health.

###

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

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Penn Researcher Receives Prestigious National Clinical Research Award for Breakthrough in Gene Therapy

SEATTLE--(BUSINESS WIRE)--

BEATBio, a Seattle, Wash.-based biotechnology company focused on the development of a novel gene therapy to improve cardiac performance in the setting of heart failure, today announced the closing of a $2.5 million seed stage investment with funding provided by CET Capital Partners. Participating investors include the W Fund. The proceeds will be used to move BEATBios lead gene therapy product into clinical development.

BEATBios therapeutic strategy is based on our founders discovery that a small increase in a naturally occurring enzyme can act as a super-fuel to increase the pumping power of heart muscles and improve cardiac performance measures including speed and force of contraction as well as relaxation in both resting and stressed states. BEATBios technology was developed by an interdisciplinary research team at the University of Washington led by Charles Murry, Director of the UW Center for Cardiovascular Biology and was funded by significant federal grants from the National Institutes of Health. BEATBio holds an exclusive global license to a suite of cardiovascular technologies from the UW, including the gene therapy program.

This financing is an important milestone for BEATBio and will allow us to move rapidly forward with the development of our lead product. It is reassuring to know that high quality, promising but early stage companies can still be funded in todays investment environment. Its a testament to the founders scientific leadership and the investors willingness to fund the critical translational phase of biotech product development, said Michael Kranda, BEATBio CEO.

CET Capital Partners Managing Director, Craig E. Tall, who will join the BEATBio Board, said, The combination of the scientific foundation, the leadership team and the prospect of fundamentally transforming the treatment of heart failure patients presented a rare investment opportunity. I am pleased to have helped launch what I believe to be an important company.

SaidChad Waite, investment committee member of the W Fund and managing director at OVP Venture Partners,BEATBiois exactly the kind of early-stage investment that the W Fund was formed to make. It represents an impactful discovery from cutting edge research in Washington that could transform the prognosis for literally millions of Americans suffering from congestive heart failure. We hope this W Fund investment will help drive these groundbreaking results from a Washington laboratory toward a new and badly-needed cardiac therapy.

About BEATBio: BEATBio is a Seattle, Wash.-based biotechnology company focused on the development of a novel gene therapy for heart failure. BEATBios technologies were developed by a founding scientific team from the University of Washington. BEATBio holds an exclusive, worldwide license from the University of Washington to a suite of technologies and associated intellectual property involving cardiovascular medicine, including gene and cell therapy, bioengineered materials and biological pace-makers.

Please visit http://www.beatbiotherapeutics.com for more information.

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BEAT BioTherapeutics Corporation Closes $2.5MM Seed Financing to Develop Its Gene Therapy Treatment for Heart Failure

GC NEWS Gene Therapy Newscast
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GM Human Gene Therapy
Class project on human gene therapy.

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Human Gene Therapy

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Human Gene Therapy - Video

BOGOTA, Colombia, April 12, 2013 /PRNewswire/ -- Startup biotechnology company Neuralgene (http://neuralgene.com) has announced that it will begin animal studies in May to evaluate the efficacy of PRCN-829, its new gene therapy agent for the treatment of amyotrophic lateral sclerosis (ALS). PRCN-829 is the first gene therapy for sporadic ALS.

(Photo: http://photos.prnewswire.com/prnh/20130412/PH93428-a )

(Photo: http://photos.prnewswire.com/prnh/20130412/PH93428-b )

Neuralgene's neurotropic AAV-based gene therapy platform for the treatment of neurodegenerative diseases is based on the stem cell work performed by Jason Williams, M.D., founder and CEO of Neuralgene. "This technology addresses several key aspects of the underlying pathology of ALS," said Leonardo Gonzalez, M.D., clinical researcher for Neuralgene. "In his stem cell work, Dr. Williams had identified that production of Factor H by fat-derived mesenchymal stem cells may be a key mode of action."

The gene therapy is based on Dr. Williams' discovery that certain proteins produced by stem cells inhibit the attack of ALS. During the development of the gene therapy, he added new targets: neural growth factors and a protein implicated in ALS named TDP-43. "When Dr. Williams demonstrated the concept behind stem cells and how to address the treatment of ALS using gene therapy, we immediately knew that this was a revolutionary new concept," said Dr. Gonzalez.

The PRCN-829 gene therapy is designed to not only target gene delivery to the brain and spinal cord, but also to genetically engineer stem cells. The AAV9 viral vector delivers multiple genes, which include Factor H (a regulator of complement activity), neural growth factors and regulators of TDP-43, to the neural cells. Initial animal studies have demonstrated the safety of the gene therapy platform.

"The problem with stem cell therapy for ALS is that the results are generally partial and temporary," stated Dr. Williams. "This is because the stem cells produce the growth factors and other proteins for a short period, but then cease. Several stem cell studies have confirmed this. Now with gene therapy, we can increase those factors by a millionfold or greater so that recuperation lasts for many years or maybe is even lifelong."

"ALS is a complex disease with many different underlying causes," continued Dr. Williams. "Our gene therapy will target several of the main underlying mechanisms related to ALS with the hopes of getting a good response in a larger group of patients. However, our platform is versatile, allowing us to change and add different target genes. We expect that soon we will be able to perform a detailed genetic analysis of the patient, identifying their exact underlying cause of ALS. Then we will be able to tailor the therapy to each individual patient."

The company has partnered with several labs for the development of its patent-pending neurotropic AAV-based gene therapy for the treatment of neurodegenerative diseases such as ALS. In fact, Neuralgene partnered with Dr. Williams' imaging and image guided treatment facility, Precision StemCell in Bogota, to begin studies using image-guided administration of gene therapy to the spinal cord.

"This is a completely new therapy for ALS, and the groundwork for this technology will lead to the treatment of many other diseases," said Dr. Williams. Neuralgene has several other AAV gene therapies in its research and development pipeline for the treatment of neurodegenerative diseases such as Parkinson's and Multiple Sclerosis (MS). After initial testing of PRCN-829 in Colombia, Neuralgene plans to seek approval from the FDA for trials in the United States.

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Gene Therapy Developed for ALS Treatment: New Biotech Company Neuralgene Enters Evaluation Phase

Daily Biology! Gene Therapy
This video is created by Jeremy Frenette Lavergne and Pedro Do Couto Bordignon. It talks about Gene therapy in a VERY general manner. We thought that most of...

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Daily Biology! Gene Therapy - Video

Gene Therapy with Jennifer Lawrence Harvey Specter
New Project.

By: John Abbott

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Gene Therapy with Jennifer Lawrence

ACGT today announced that seed money provided for innovative T-Cell immunotherapy cell and gene therapy research has led to two successful Clinical Trials for treatment of Acute Lymphoblastic Leukemia resulting in remissions in both children and adults who had no other hope of recovery.

Stamford, Connecticut (PRWEB) April 08, 2013

According to Michel Sadelain, MD, PhD, ACGT Scientific Advisory Council member and Research Fellow, and senior author of the Acute Lymphoblastic Leukemia study published March 21st in the journal Science Translational Medicine, This is a very exciting finding for patients and a major achievement in the field of targeted immunotherapy. Sadelain explained that these successful treatments would not have been possible had not been for the startup funding from ACGT. It wasnt easy to get funding to support such innovative, unproved therapies. The grant from ACGT was our first major grant to launch our T-cell program. Dr. Sadelain is the Director of the Center for Cell Engineering and Gene Transfer Expression Laboratory at Memorial Sloan-Kettering Cancer Center.

Dr. Sadelain, and Dr. Carl H. June, Perelman School of Medicine at the University of Pennsylvania, were each awarded $1 million in ACGT Clinical Investigator grants in 2004 to fund research using immune-mediated gene therapy for the treatment of lymphoma or leukemia. They were the first two Clinical Translational grants that ACGT awarded. Just last week, ACGT received 49 letters of intent, with a majority focused on T-cell therapy research, in response to its Request for Applications for 2013 Clinical Translational grants that will be awarded this Spring.

Dr. June, ACGT Scientific Advisory Council member and leader of the team that successfully treated two young leukemia patients, Emma Whitehead and Maddie Major, and seven other adult leukemia patients at the Abramson Cancer Center of the University of Pennsylvania (Penn) also commented on the cutting-edge research ACGT supported: "Funding was not available from the National Institutes of Health (NIH) for gene therapy (in 2004). ACGT was the first to be there, to say that cell and gene therapies can be a new platform therapy, and giving literally lifesaving grants to scientists who cannot get them from the federal system."

ACGT is the only not-for-profit in the U.S. solely dedicated to cancer cell and gene therapy treatments for all types of cancer. 100% of contributions go directly to research. ACGT has funded 41 grants since its founding in 2001 totaling almost $24 million to fund both basic research and clinical translation. ACGT's Scientific Advisory Council, comprised of 16 renowned physicians and researchers, conducts a rigorous review process. Seventeen ACGT funded research projects have been approved for human clinical trials, 11 of which are underway. To donate, please visit http://www.acgtfoundation.org or call 203.358.8000.

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Deborah Burns, 203.257.3163

deborah(at)burnscommunications(dot)net

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ACGT Provides Seed Money for T-Cell Immunotherapy Cell and Gene Therapy Research; Successful Clinical Trials for ...

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PARIS, April 8, 2013 /PRNewswire/ --

GenSight Biologics, a biopharmaceutical company focused on the development of ophthalmic therapeutics using gene therapy, announced today the closing of a 32 million Series A financing.

The financing was co-led by Novartis Venture Fund, Abingworth LLP, Versant Ventures and Index Ventures. GenSight will use the funds to develop a gene replacement therapy for Leber's hereditary optic neuropathy (LHON) and an optogenetic therapy for retinitis pigmentosa (RP). The lead product is expected to enter the clinic in 2013 in LHON patients.

Bernard Gilly, co-founder and CEO of GenSight is a successful bio-entrepreneur, was formerly CEO of Fovea Pharmaceuticals (which was acquired by sanofi-aventis in 2009), a partner at Sofinnova Partners and CEO of Transgene, a publicly traded gene therapy company. GenSight co-founder, Professor Jos-Alain Sahel, is Chairman of the Vision Institute in Paris. Botond Roska, a specialist in the structure and function of neural circuits at the FMI (Basel), has been pioneering the field of optogenetics. Jean Bennett, Professor of Ophthalmology, University of Pennsylvania, and also a co-founder of GenSight, has successfully conducted gene therapy trials to treat a rare retinal degeneration. The other co-founders of GenSight are Connie Cepko Professor of Genetics at Harvard (Boston), Ernst Bamberg Professor at The Max Planck Institute (Frankfurt), Luk Vandenberghe at the Schepens Eye Research Institute(Boston) and Serge Picaud at the Vision Institute (Paris).

Bernard Gilly commented: "Gene therapy is coming of age and ophthalmology is one of the most promising indications in particular because of the safety and efficacy demonstrated in certain trials. GenSight has a unique, proprietary approach to targeting the mitochondria in LHON developed by Dr Corral-Debrinsky and Jose Sahel at the Vision Institute, and exclusive access to key intellectual property from Novartis for using optogenetics to treat RP patients. Our outstanding links to leading ophthalmology physicians and scientists on both sides of the Atlantic, our strong link with the Foundation Fighting Blindness, our partnership with AFM/Genethon and our experienced management team are key to successfully moving our products through clinical developments to proof of efficacy."

"We are delighted to be working with GenSight and the other investors to assist the company in progressing its highly innovative technology and gene-based therapeutics towards the clinic. Gene therapy represents a new frontier in targeting ophthalmic diseases, and GenSight's expertise and capabilities are outstanding," said Florent Gros of Novartis Venture Fund, who will join the board of directors, along with Dr Genghis Lloyd-Harris (Abingworth) and Dr Guido Magni (Versant).

GenSight is based in Paris, France on the campus of the Vision Institute. Please visit our website http://www.gensight-biologics.com

Notes for Editors

About Novartis Venture Fund

The Novartis Venture Funds manages over $850 million in committed capital. NVF invests in companies which have the potential to change a core therapeutic field or explore new business areas that will be critical to patient care. Our primary interest is in the development of novel therapeutics and platforms as well as medical devices, diagnostics, and delivery systems. The Funds invest for financial objectives at all stages, but prefers to invest in the early-stages of company development. With ten investment professionals located in Basel, Switzerland and Cambridge, MA the team has extensive experience in pharmaceutical R&D and venture capital.

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GenSight Biologics Raises €32m in a Series A Financing for Ophthalmic Gene Therapy

London, UK - Fertility regulators in the UK have paved the way for the introduction of a radical form of gene therapy in which babies are created using cellular material from three people.

The Human Fertilisation and Embryology Authority (HFEA) advised the government recently that there is no evidence "mitochondrial replacement" - an advanced form of in-vitro fertilisation - is unsafe, and ministers will now decide whether to proceed with the technique.

Critics say the move is the first step on a slippery slope towards the creation of "designer babies" built to order that heralds a new era of "consumer eugenics" - with potentially disastrous implications for humankind.

"There has been a consensus for some time in about 50 or 60 countries that we should not manipulate the human 'germline' - that is, the cells that give rise to a new individual," saidDr David King, director of the group Human Genetics Alert.

"This is the first time that there has been official approval for crossing that line and, once you cross the Rubicon, it becomes difficult not to move to the next stage - full-fledged enhancement, genetic engineering."

Mitochondria are cigar-shaped components of body cells that provide them with energy. If they are defective, it can starve the body of energy, leading to muscle weakness, blindness, deafness, epilepsy, heart failure, early dementia and even death.

Some form of mitochondrial disease affects about one in 200 children born each year - or a few dozen babies in Britain.

The proposed therapy targets women who harbour harmful mitochondrial DNA mutations, but who want to have their own genetic offspring instead of relying on a donated egg.

The treatment would take a donated egg cell then remove its nucleus and chromosomes containing the genetic information, but retain its healthy mitochondria. The nucleus from the egg of an affected mother would be inserted into it - either before or after fertilisation - and the fertilised egg would then be implanted in the mother's womb.

A baby born as a result should be free of the mother's mitochondrial defects - and that child's own eventual offspring should also be free of these, changing the genetic line for ever.

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New gene therapy births 'designer baby' fears

SP1202 Draft - Gene Therapy
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Washington, Mar. 27 (ANI): Researchers have shown that it is possible to use gene therapy to treat patients whose hearts have been weakened by cardiac arrests and other heart conditions.

The research group was led by University of Washington (UW) Professor and Vice Chair of Bioengineering Michael Regnier and Dr. Chuck Murry, director of the Center for Cardiovascular Biology and co-director of the Institute for Stem Cell and Regenerative Medicine at UW.

Normally, muscle contraction is powered by a molecule, the nucleotide called Adenosine-5'-triphosphate (ATP).

In a previous study of isolated muscle, Regnier, Murry and colleagues had found that one naturally occurring molecule, called 2 deoxy-ATP (dATP), was actually more effective than ATP in boosting muscle contraction, increasing both the speed and force of the contraction, at least over the short-term.

In the new study, the researchers wanted to see if this effect could be sustained. For this, they used genetic engineering to create a strain of mice whose cells produced higher-than-normal levels of an enzyme called Ribonucleotide Reductase that converts the precursor of ATP, adenosine-5'-diphosphate or ADP, to dADP, which, in turn, is rapidly converted to dATP.

The researchers found that increased production of the enzyme Ribonucleotide Reductase increased the concentration of dATP within heart cells approximately tenfold, and even though this level was still less than one to two percent of the cell's total pool of ATP, the increase led to a sustained improvement in heart muscle function, with the genetically engineered hearts contracting more quickly and with greater force.

"The same pathway that heart cells use to make the building blocks for DNA during embryonic growth makes dATP to supercharge contraction when the adult heart is mechanically stressed," Murry said.

Importantly, the elevated dATP effect was achieved without imposing additional metabolic demands on the cells, suggesting the modification would not harm the cell's functioning over the long-term.

The findings suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for heart failure.

The study has been published in the journal Proceedings of the National Academy of Sciences (PNAS). (ANI)

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Gene therapy may help restore heart function after attack

WITHIN just eight days of starting a novel gene therapy, David Aponte's "incurable" leukaemia had vanished. For four other patients, the same happened within eight weeks, although one later died from a blood clot unrelated to the treatment, and another after relapsing.

The cured trio, who were all previously diagnosed with usually fatal relapses of acute lymphoblastic leukaemia, have now been in remission for between 5 months and 2 years. Michel Sadelain of the Memorial Sloan-Kettering Cancer Center in New York, co-leader of the group that designed the trial, says that a second trial of 50 patients is being readied, and the team is looking into using the technique to treat other cancers.

The key to the new therapy is identifying a molecule unique to the surface of cancer cells, then genetically engineering a patient's immune cells to attack it.

In acute lymphoblastic leukaemia, immune cells called B-cells become malignant. The team were able to target a surface molecule known as CD19 that is only present on B-cells. Doctors extracted other immune cells called T-cells from the patients. These were treated with a harmless virus, which installed a new gene redirecting them to attack all cells bearing CD19. When the engineered T-cells were reinfused into the patients, they rapidly killed all B-cells, cancerous or otherwise.

"The stunning finding was that in all five patients, tumours were undetectable after the treatment," says Sadelain.

He reckons that the body should replenish the immune system with regular T-cells and healthy B-cells after a couple of months. However, the patients received donated bone marrow to ensure they could regrow a healthy immune system (Science Translational Medicine, doi.org/kwz).

The treatment is not the first to re-engineer T-cells to attack a form of leukaemia. Last year, an international company called Adaptimmune used the approach to treat 13 people with multiple myeloma it left 10 in remission.

"Although it's early days for these trials, the approach of modifying a patient's T-cells to attack their cancer is looking increasingly like one that will, in time, have a place alongside more traditional treatments," says Paul Moss of Cancer Research UK.

Sadelain's team is now investigating the scope for attacking other cancers. Where no single surface molecule is unique to a cancer, he is seeking to target pairs of molecules that only occur together on cancer cells. In January, he demonstrated this approach by wiping out human prostate tumours implanted in mice, using T-cells engineered to target two surface molecules (Nature Biotechnology, doi.org/kw2).

If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.

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Mar. 25, 2013 In an animal study, researchers at the University of Washington show that it was possible to use gene therapy to boost heart muscle function. The finding suggests that it might be possible to use this approach to treat patients whose hearts have been weakened by heart attacks and other heart conditions.

Led by University of Washington (UW) Professor and Vice Chair of Bioengineering Michael Regnier and Dr. Chuck Murry, director of the Center for Cardiovascular Biology and co-director of the Institute for Stem Cell and Regenerative Medicine at UW, the study appears online today in the journal Proceedings of the National Academy of Sciences (PNAS).

Normally, muscle contraction is powered by a molecule, the nucleotide called Adenosine-5'-triphosphate (ATP). Other naturally occurring nucleotides can also power muscle contraction, but, in most cases, they have proven to be less effective than ATP.

In an earlier study of isolated muscle, however, Regnier, Murry and colleagues had found that one naturally occurring molecule, called 2 deoxy-ATP (dATP), was actually more effective than ATP in powering muscle contraction, increasing both the speed and force of the contraction, at least over the short-term.

In the new PNAS study, the researchers wanted to see whether this effect could be sustained. To do this, they used genetic engineering to create a strain of mice whose cells produced higher-than-normal levels of an enzyme called Ribonucleotide Reductase, which converts the precursor of ATP, adenosine-5'-diphosphate or ADP, to dADP, which, in turn, is rapidly converted to dATP.

"This fundamental discovery, that dATP can act as a 'super-fuel' for the contractile machinery of the heart, or myofilaments, opens up the possibility to treat a variety of heart failure conditions," Regnier said. "An exciting aspect of this study and our ongoing work is that a relatively small increase in dATP in the heart cells has a big effect on heart performance."

The researchers found that increased production of the enzyme Ribonucleotide Reductase increased the concentration of dATP within heart cells approximately tenfold, and even though this level was still less than one to two percent of the cell's total pool of ATP, the increase led to a sustained improvement in heart muscle function, with the genetically engineered hearts contracting more quickly and with greater force.

"It looks as though we may have stumbled on an important pathway that nature uses to regulate heart contractility," Murry added. "The same pathway that heart cells use to make the building blocks for DNA during embryonic growth makes dATP to supercharge contraction when the adult heart is mechanically stressed."

Importantly, the elevated dATP effect was achieved without imposing additional metabolic demands on the cells, suggesting the modification would not harm the cell's functioning over the long-term.

The finding, the authors write, suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for heart failure.

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Gene therapy may aid failing hearts