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

Contact: Raymond MacDougall macdougallr@mail.nih.gov 301-402-0911 NIH/National Human Genome Research Institute

Researchers have demonstrated that a refined gene therapy approach safely restores the immune systems of some children with severe combined immunodeficiency (SCID). The rare condition blocks the normal development of a newborn's immune system, leaving the child susceptible to every passing microbe. Children with SCID experience chronic infections, which usually triggers the diagnosis. Their lifespan is two years if doctors cannot restore their immunity.

The findings from facilities including the National Institutes of Health, the University of California, Los Angeles (UCLA), and the Children's Hospital Los Angeles, are reported in the Sept. 11, 2012, advanced online issue of the journal Blood, the official journal of the American Society of Hematology.

In the 11-year study, the researchers tested a combination of techniques for gene therapy, arriving at one that produced normal levels of immune function for three patients.

"Doctors who treat patients with SCID have had limited treatment options for too long," said Dan Kastner, M.D., Ph.D., scientific director of the National Human Genome Research Institute (NHGRI), part of the NIH. "The research teams and the patients who have participated in the studies have together achieved an impressive advance toward a cure that is welcome news for both the scientific and patient communities."

Gene therapy is an experimental method for treating patients with genetic diseases. It is intended to integrate functioning genes among those naturally existing in the cells of the body to make up for faulty genes. Researchers in the current study tested a set of methods to improve outcomes for children with a particular form of SCID.

"This is a highly rewarding study for those of us in the clinic and lab," said Fabio Candotti, M.D., a senior author and a senior investigator in NHGRI's Genetics and Molecular Biology Branch. "Not only have we realized an important advancement in gene therapy, but we have seen a renewal of health in our patients."

While rare, SCID became widely known because of the remarkable boy-in-the-bubble story of the 1970s. The story was based in part on a boy named David Vetter, who lived for 13 years in a plastic isolation unit to protect him from infections. He died following an unsuccessful bone marrow transplant that doctors had hoped would repair his immune system.

SCID has many causes. In one type, a gene that produces the adenosine deaminase (ADA) enzyme becomes mutated and fails to produce the normal enzyme. Without ADA, a chemically altered form of adenosine, one of DNA's building blocks, accumulates in rapidly dividing bone marrow cells, killing them and destroying the immune system in the process. Normal bone marrow makes healthy white blood cells, or lymphocytes, which are the key players in the immune response that reacts against harmful bacteria and destroys cells infected by viruses. ADA deficiency accounts for some 15 percent of SCID cases.

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NIH researchers restore children's immune systems with refinements in gene therapy

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

Contact: Claire Gwayi-Chore cgwayi-chore@hematology.org 202-776-0544 American Society of Hematology

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

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

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

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

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

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

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

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

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Researchers improve gene therapy technique for children with immune disorder

London, September 8 (ANI): Offering hope to people who can't smell anything from birth or lose it due to disease, scientists have restored the sense of smell in mice through gene therapy for the first time.

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Gene therapy restores sense of smell in mice for 1st time

Public release date: 7-Sep-2012 [ | E-mail | Share ]

Contact: Cathy Kolf ckolf@jhmi.edu 443-287-2251 Johns Hopkins Medicine

A team of scientists from Johns Hopkins and other institutions report that restoring tiny, hair-like structures to defective cells in the olfactory system of mice is enough to restore a lost sense of smell. The results of the experiments were published online this week in Nature Medicine, and are believed to represent the first successful application of gene therapy to restore this function in live mammals.

An expert in olfaction, Randall Reed, Ph.D., professor of molecular biology and genetics and co-director of the Center for Sensory Biology at the Johns Hopkins Institute for Basic Biomedical Sciences, cautions that researchers are still years away from applying the same therapy in people, and that if and when it comes, it will likely be most effective for those who suffer from anosmia (lack of smell) due to inherited genetic disorders. "But our work has already contributed to a better understanding of the cellular factors involved in anosmia, and that will give us insights into other neurological disorders, as well," he says.

The mice used in the current study carried a genetic mutation that destroyed the production of a protein critical for the functioning of cilia in the cells responsible for smell, called olfactory sensory neurons. These specialized cells each display several of the protruding, hair-like structures that contain receptors for odorants. Without functional cilia, the cells become a broken link in the chain of events necessary for proper odor detection in the environment, the researchers explained.

Beginning with a common cold virus, which readily infects the cells of the nasal cavity, researchers replaced some of the viral genes with a corrected version of the defective cilia gene. They then infected smelling-impaired mice with the altered virus, delivering the corrected gene to the olfactory neural cells that needed it.

At the cellular level, scientists saw a restoration of proper chemical signaling between nerve cells after the treated mice were stimulated with various odorants. Perhaps even more indicative of their success, Reed says, was the 60 percent increase in body weight that the mice experienced once they could smell their meals, leading to increased appetite. Many people with anosmia lose weight because aromas play a significant part in creating appetite and food enjoyment.

Researchers are optimistic about the broader implications of this work, Reed notes, because cilia are not only important to olfactory cells, but also to cells all over the body, from the kidney to the eye. The fact that they were able to treat live mice with a therapy that restored cilia function in one sensory system suggests that similar techniques could be used to treat cilia disorders elsewhere.

"We also hope this stimulates the olfactory research community to look at anosmia caused by other factors, such as head trauma and degenerative diseases," says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at the University of Michigan. "We know a lot about how this system works now have to look at how to fix it when it malfunctions."

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The nose knows: Gene therapy restores sense of smell in mice

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/96czlk/gene_therapy_tec) 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.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2011, over 2030 clinical trials have been completed, are ongoing or have been approved worldwide.A breakdown of these trials is shown according to the areas of application.

Since the death of Jesse Gelsinger in the US following a gene therapy treatment, the FDA has further tightened the regulatory control on gene therapy. A further setback was the reports of leukemia following use of retroviral vectors in successful gene therapy for adenosine deaminase deficiency. Several clinical trials were put on hold and many have resumed now. The report also discusses the adverse effects of various vectors, safety regulations and ethical aspects of gene therapy including germline gene therapy.

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 2011-2021. 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 700 references are appended in the bibliography.The references are constantly updated. The text is supplemented with 72 tables and 14 figures.

Profiles of 187 companies involved in developing gene therapy are presented along with 208 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.

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Research and Markets: Gene Therapy - Technologies, Markets and Companies - Updated 2012 Report

ScienceDaily (Sep. 5, 2012) That low bone density causes osteoporosis and a risk of fracture is common knowledge. But an excessively high bone density is also harmful. The most serious form of excessively high bone density is a rare, hereditary disease which can lead to the patient's death by the age of only five. Researchers at Lund University in Sweden are now trying to develop gene therapy against this disease.

In order for the body to function, a balance is necessary between the cells that build up the bones in our skeletons and the cells that break them down. In the disease malignant infantile osteopetrosis, MIOP, the cells that break down the bone tissue do not function as they should, resulting in the skeleton not having sufficient cavities for bone-marrow and nerves.

"Optic and auditory nerves are compressed, causing blindness and deafness in these children. Finally the bone marrow ceases to function and, without treatment, the child dies of anemia and infections," explains Carmen Flores Bjurstrm. She has just completed a thesis which presents some of the research at the division for Molecular Medicine and Gene Therapy in Lund.

The researchers' work focuses on finding alternatives to the only treatment currently available against MIOP, namely a bone-marrow transplant. This treatment can be effective, but it is both risky and dependent on finding a suitable donor.

Gene therapy requires no donor, as stem cells are taken from the patients themselves. Once the cells' non-functioning gene has been replaced with a healthy copy of itself, the stem cells are put back into the patient.

Great hopes have been placed on gene therapy as a treatment method but the work has proven to be more difficult than expected. The method is used today for certain immunodeficiency diseases, and has also been applied to a blood disorder called thalassemia.

"So far, the method is not risk-free. Since it is impossible to control where the introduced gene ends up, there is a certain risk of it ending up in the wrong place and giving rise to leukemia. This is why gene therapy is only used for serious diseases for which there is no good treatment," says Carmen Flores Bjurstrm.

The Lund researchers have conducted experiments with gene therapy in both patient cells and laboratory animals. The next step is to conduct trials on patients. The trials will probably take place at the hospital in Ulm, Germany, which currently treats the majority of children in Europe suffering from MIOP.

MIOP is a rare disease: in Sweden a child is born with the condition approximately once every three years. Worldwide, the incidence of the disease is one case for every 300 000 births. It is, however, more common in Costa Rica where 3-4 children per 100 000 births have the disease.

"But there are several other genetic mutations that lead to other osteopetrosis diseases. If we manage to treat MIOP, it may become possible to treat these other conditions as well," hopes Carmen Flores Bjurstrm along with her supervisor, Professor Johan Richter.

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Can gene therapy cure fatal diseases in children?

Washington, Sep 3 (IANS) Scientists have restored olfactory sense in mice through gene therapy for the very first time - potentially opening the way for people to regain their sense of smell lost since birth or owing to disease.

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Gene therapy restores olfactory sense in mice

London, September 3 (ANI): Offering hope to people who can't smell anything from birth or lose it due to disease, scientists have restored the sense of smell in mice through gene therapy for the first time.

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Gene therapy restores sense of smell in mice

Public release date: 2-Sep-2012 [ | E-mail | Share ]

Contact: Robin Latham lathamr@nidcd.nih.gov 301-496-7243 NIH/National Institute on Deafness and Other Communication Disorders

Scientists funded by the National Institutes of Health have restored the ability to smell in a mouse model of a human genetic disorder that causes congenital anosmiathe inability to smell from birth. The approach uses gene therapy to regrow cilia, cell structures that are essential for olfactory function. The study was funded by four parts of NIH: the National Institute on Deafness and Other Communications Disorders (NIDCD), the National Institute on Diabetes and Digestive and Kidney Diseases (NIDDK), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Eye Institute (NEI). It was published online in the September 2, 2012, issue of the journal Nature Medicine.

"These results could lead to one of the first therapeutic options for treating people with congenital anosmia," said James F. Battey, Jr., M.D., Ph.D., director of NIDCD. "They also set the stage for therapeutic approaches to treating diseases that involve cilia dysfunction in other organ systems, many of which can be fatal if left untreated."

Olfactory dysfunction can be a symptom of a newly recognized class of genetic disorders, known as ciliopathies, which include diseases as diverse as polycystic kidney disease and retinitis pigmentosa, an inherited, degenerative eye disease that causes severe vision impairment and blindness. The disorders are caused by defects in cilia, antenna-like projections on cells that help them sense their environment. Scientists believe that nearly every cell in the body has the capacity to grow one or more cilia. In the olfactory system, multiple cilia project from olfactory sensory neurons, sensory cells that are found in the olfactory epithelium, tissue high up in the nasal cavity. Receptors that bind odorants are localized on the cilia, which is why a loss of cilia results in a loss in the ability to smell.

The team of researchers, led by Jeffrey R. Martens, Ph.D., at the University of Michigan, Ann Arbor, and Jeremy C. McIntyre, Ph.D., a post-doctoral fellow in Martens' laboratory, worked with a mouse model carrying a mutation in the IFT88 gene. The mutation causes a decrease in the IFT88 protein, which leads to a dramatic reduction in cilia function in several different organ systems, including the olfactory system.

The researchers used an adenovirus to introduce a healthy copy of the gene as a way to restore IFT88 protein levels in the mice. They wanted to see if the reintroduction of the lost protein could restore cilia to the olfactory sensory neurons and return the ability to smell. For three consecutive days, the mice received intranasal gene delivery therapy and then were allowed 10 days for the infected sensory neurons to express the viral-encoded IFT88 protein. After that time, the mice were tested with increasing concentrations of an odorant (amyl acetate). Their responses were measured at the cellular, tissue, and synaptic levels, which all indicated that the mice had regained olfactory function.

"By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants," said McIntyre.

The change in olfactory function also has implications in the feeding behavior of the mice. The mouse model the scientists used is born underweight and its anosmia interferes with the motivation to eat, which in many mammals, including humans, is driven by smell. Treatment with adenovirus therapy increased bodyweight by 60 percent in treated compared to untreated mice, indicating that the restored olfactory function was motivating feeding.

The researchers plan to continue their work by developing another mouse model to look at the impact on olfactory function and the potential for restoring function when the IFT88 gene is completely missing, rather than just mutated. Future studies could begin to plot a way to bring this therapeutic tactic to human study volunteers, which could eventually restore the sense of smell, and a better quality of life, to people who are born with anosmia. Further research could also advance the treatments for other ciliopathies, as these findings show that gene therapy is a viable option for the functional rescue of cilia in established, already differentiated cells.

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NIH-funded researchers restore sense of smell in mice using genetic technique

ScienceDaily (Sep. 2, 2012) Scientists have restored the sense of smell in mice through gene therapy for the first time -- a hopeful sign for people who can't smell anything from birth or lose it due to disease.

The achievement in curing congenital anosmia -- the medical term for lifelong inability to detect odors -- may also aid research on other conditions that also stem from problems with the cilia. Those tiny hair-shaped structures on the surfaces of cells throughout the body are involved in many diseases, from the kidneys to the eyes.

The new findings, published online in Nature Medicine, come from a team at the University of Michigan Medical School and their colleagues at several other institutions.

The researchers caution that it will take time for their work to affect human treatment, and that it will be most important for people who have lost their sense of smell due to a genetic disorder, rather than those who lose it due to aging, head trauma, or chronic sinus problems. But their work paves the way for a better understanding of anosmia at the cellular level.

"Using gene therapy in a mouse model of cilia dysfunction, we were able to rescue and restore olfactory function, or sense of smell," says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at U-M. "Essentially, we induced the neurons that transmit the sense of smell to regrow the cilia they'd lost."

The mice in the study all had a severe genetic defect that affected a protein called IFT88, causing a lack of cilia throughout their bodies. Such mice are prone to poor feeding and to early death as a result. In humans, the same genetic defect is fatal.

The researchers were able to insert normal IFT88 genes into the cells of the mice by giving them a common cold virus loaded with the normal DNA sequence, and allowing the virus to infect them and insert the DNA into the mouse's own cells. They then monitored cilia growth, feeding habits, and well as signals within and between the nerve cells, called neurons, that are involved in the sense of smell.

Only 14 days after the three-day treatment, the mice had a 60 percent increase in their body weight, an indication they were likely eating more. Cell-level indicators showed that neurons involved in smelling were firing correctly when the mice were exposed to amyl acetate, a strong-smelling chemical also called banana oil.

"At the molecular level, function that had been absent was restored," says Martens.

"By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants," says postdoctoral fellow and first author Jeremy McIntyre, Ph.D.

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Can’t smell anything? Discovery may give you hope

Public release date: 2-Sep-2012 [ | E-mail | Share ]

Contact: Kara Gavin kegavin@umich.edu 734-764-2220 University of Michigan Health System

ANN ARBOR, Mich. Scientists have restored the sense of smell in mice through gene therapy for the first time -- a hopeful sign for people who can't smell anything from birth or lose it due to disease.

The achievement in curing congenital anosmia -- the medical term for lifelong inability to detect odors -- may also aid research on other conditions that also stem from problems with the cilia. Those tiny hair-shaped structures on the surfaces of cells throughout the body are involved in many diseases, from the kidneys to the eyes.

The new findings, published online in Nature Medicine, come from a team at the University of Michigan Medical School and their colleagues at several other institutions.

The researchers caution that it will take time for their work to affect human treatment, and that it will be most important for people who have lost their sense of smell due to a genetic disorder, rather than those who lose it due to aging, head trauma, or chronic sinus problems. But their work paves the way for a better understanding of anosmia at the cellular level.

"Using gene therapy in a mouse model of cilia dysfunction, we were able to rescue and restore olfactory function, or sense of smell," says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at U-M. "Essentially, we induced the neurons that transmit the sense of smell to regrow the cilia they'd lost."

The mice in the study all had a severe genetic defect that affected a protein called IFT88, causing a lack of cilia throughout their bodies. Such mice are prone to poor feeding and to early death as a result. In humans, the same genetic defect is fatal.

The researchers were able to insert normal IFT88 genes into the cells of the mice by giving them a common cold virus loaded with the normal DNA sequence, and allowing the virus to infect them and insert the DNA into the mouse's own cells. They then monitored cilia growth, feeding habits, and well as signals within and between the nerve cells, called neurons, that are involved in the sense of smell.

Only 14 days after the three-day treatment, the mice had a 60 percent increase in their body weight, an indication they were likely eating more. Cell-level indicators showed that neurons involved in smelling were firing correctly when the mice were exposed to amyl acetate, a strong-smelling chemical also called banana oil.

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Can't smell anything? This discovery may give you hope

The technique would retrain cells that typically don't respond to light.

Kiji McCafferty

One biotech startup wants to restore vision in blind patients with a gene therapy that gives light sensitivity to neurons that don't normally possess it.

The attempt, by Ann Arbor, Michigan-based Retrosense Therapeutics, will use so-called optogenetics. Scientists have used the technique over the last few years as a research tool to study brain circuits and the neural control of behavior by directing neuron activity with flashes of light. But Retrosense and others groups are pushing to bring the technique to patients in clinical trials.

The idea behind Retrosense's experimental therapy is to use optogenetics to treat patients who have lost their vision due to retinal degenerative diseases such as retinitis pigmentosa. Patients with retinitis pigmentosa experience progressive and irreversible vision loss because the rods and cones of their eyes die due to an inherited condition. If the company is successful, the treatment could also help patients with the most common form of macular degeneration, which affects nearly a million people in the United States. The U.S. Food and Drug Administration hasn't approved any therapies for either condition.

Retrosense is developing a treatment in which other cells in the retina could take the place of the rods and cones, cells which convert light into electrical signals. The company is targeting a group of neurons in the eye called ganglion cells. Normally, ganglion cells don't respond to light. Instead, they act as a conduit for electrical information sent from the retina's rods and cones. The ganglion cells then transmit visual information directly to the brain.

Doctors would inject a non-disease causing virus into a patient's eye. The virus would carry the genetic information needed to produce the light-sensitive channel proteins in the ganglion cells. Normally, rods, cones, and other cells translate light information into a code of neuron-firing patterns that is then transmitted via the ganglion cells into the brain. Since Retrosense's therapy would bypass that information processing, it may require the brain to learn how to interpret the signals.

So far, Retrosense and its academic collaborators have shown that the treatment can restore some vision-evoked behaviors in rodents. The treatment also seems safe in nonhuman primates. The optogenetically modified ganglion cells of these primates are light-responsive, but behavioral tests aren't possible, as there are no nonhuman primate models of retinal degeneration, says Retrosense CEO Sean Ainsworth.

Retrosense plans to begin its first clinical trial in 2013 with nine blind retinitis pigmentosa patients.

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Company Aims to Cure Blindness with Optogenetics

Neuropathic pain associated with diabetes, shingles, and traumatic injury affects up to 18 percent of the population and can be difficult or impossible to effectively treat. Using gene therapy, Yale neurologists have managed to repair neurons associated with traumatic nerve injury pain in rats.

Since the therapy targets only cells in the pain-sensing neurons outside the brain and spinal cord, this method can avoid some of cognitive problems associated with other pain therapies that also work on the central nervous system, said Omar Samad, research scientist in neurology and lead author of the paper published online Aug. 21 in the journal Molecular Therapy.

The work was conducted in the laboratory of Stephen Waxman, the Bridget M. Flaherty Professor of Neurology and director of the center for neuroscience and regeneration research, and it was supported by the Department of Veterans Affairs and the Nancy Taylor Foundation for Chronic Diseases.

Other authors are Andrew Tan, Xiaoyang Chen, Edmund Foster, and Sulayman Dib-Hajj.

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Research in the News: Gene therapy shows promise in neuron repair and pain relief

ScienceDaily (Aug. 21, 2012) Numerous viruses are used in the service of science today. They serve as gene taxis to transfer therapeutic genes into body cells or as therapeutic viruses targeted to infect and destroy cancer cells. For such applications, the viruses are often equipped with additional genes, such as for immune mediators or for proteins inducing programmed cell death. However, these gene products can harm the body if they are released at the wrong moment or at excessive levels. "Ideally, we want to be able to turn on and off the transferred genes at a specific time," says Dr. Dirk Nettelbeck, a virologist from DKFZ.

To this end, Patrick Ketzer of Nettelbeck's group experimented, jointly with colleagues from Konstanz University, with what are called RNA switches. In order to construct such a switch, the researchers inserted synthetic segments of DNA into the viral genetic material in the direct vicinity of the transferred gene. In the infected cell, this construct is transcribed together with the transferred gene into a single messenger RNA (mRNA) molecule. The switch is operated using an agent which is added to cells infected with the virus. The substance is precisely fitted to bind to the RNA molecule and induces it to cut itself up. Thus, the potentially dangerous protein cannot be produced. The researchers copied this regulation mechanism from bacteria which use RNA switches to regulate production of numerous proteins.

The DKFZ virologists first constructed an RNA switch that is kept in permanent "off" position by the substance. The production of the foreign protein does not start as long as substance is added. "This was a first proof that RNA switches work in viruses at all. But it is just as well possible to construct switches that do not allow production of the protein until the substance is added," Dirk Nettelbeck explains.

In cells, it has been possible for many years now to specifically turn on and off genes. To do so, scientists modified specific natural regulatory regions called promoters in the cellular genetic material. As a result, addition of the antibiotic tetracycline causes mRNA production to be turned on or off.

"However, this type of switch is too big and complex to be used in viruses or doesn't work there," says Dirk Nettelbeck. "The RNA switches, in contrast, are only 100 base pairs long." Using the RNA switches, the researchers managed to increase the production of the therapeutic gene by ten times. "But there is still room for a lot more," Nettelbeck explains. "The construction of RNA switches is extremely variable. Once the technology is fully developed, we will be able to better equip and regulate viruses for many therapeutic applications." Nettelbeck and his team are convinced that the useful RNA switches will become established for many other uses in research and medicine.

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The above story is reprinted from materials provided by Helmholtz Association of German Research Centres.

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Viruses with integrated gene switch

The first gene therapy drug approval given by European regulators is potentially good news for those suffering from a rare syndrome which prevents their body from breaking down fat. The decision by the European Medicines Agency to allow Dutch bio...

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First Gene Therapy Treatment Approved in Europe

The National Institutes of Health (NIH) this week awarded researchers at Allegheny General Hospital in Pittsburgh a $1.7 million grant to support the study of a pioneering approach to gene therapy that may offer new hope for the treatment of chronic illnesses. The study will initially look at its potential to treat a condition called xerostomia. ...

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NIH Awards Allegheny General Hospital Researchers $1.7 Million Grant to Study Pioneering Approach To Gene Therapy

Attorney Joseph W. Belluck says a recently reported breakthrough in gene therapy offers a ray of hope for victims of mesothelioma and other asbestos-related diseases.New York, NY (PRWEB) August 09, 2012 A regulatory green light for a gene therapy drug in Europe opens exciting new possibilities for the treatment of mesothelioma, New York lawyer Joseph W. Belluck said today.The European Medicines ...

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New York Mesothelioma Lawyer from Belluck & Fox, LLP, Hails Milestone in Gene Therapy Treatment

* Animal experiments show gene therapy can boost performance

* Gene doping likely to be dangerous and risky in humans

* Tests can't detect it, so status of gene doping unclear

LONDON, Aug 7 (Reuters) - There have been "marathon mice",

"Schwarzenegger mice" and dogs whose wasted muscles were

repaired with injected substances that switch off key genes. It

may not be long before we get the first genetically modified

athlete.

Some fear the use of gene therapy to improve athleticism is

already a reality. But since sports authorities' drug testing

Link:

FEATURE-Testers fear reality of genetically modified Olympians

CTVNews.ca Staff Published Tuesday, Jul. 31, 2012 8:46AM EDT Last Updated Tuesday, Jul. 31, 2012 8:50AM EDT

Dale Turner remembers the day his view of the world changed, literally, thanks to a groundbreaking clinical trial that partially restored his vision.

It was 2008 and the 25-year-old lawyer from Peterborough, Ont., who was diagnosed with an incurable genetic eye disease that causes blindness in childhood, was recovering from an eye surgery in Florida as part of the clinical trial.

Three days after the surgery, Turner removed his eye patch and realized his vision had been partially restored.

When I peeled back the patch, I was outside of the University of Florida on a nice bright, sunny day and I had never seen the sky like I had seen it before. It was just one of those things that the proof was right in the sight, Turner told CTVs Canada AM on Tuesday.

Turner was diagnosed with a disease called Lebers congenital amaurosis when he was six years old. The eye disease is hereditary and affects around one in 80,000 newborns and is one of the most common causes of childhood blindness.

Turners family was told by doctors that the disease would lead to total blindness by the time he was 10.

But in 2007 scientists announced they had discovered the gene mutation that was responsible for causing the blindness.

The gene is called the NMNAT1 and doctors estimate it causes around five per cent of cases of Lebers congenital amaurosis.

Turner was asked to participate in an experimental clinical trial that would treat his eye with gene therapy.

Here is the original post:

Gene therapy restores Ontario man’s vision

Washington, July 26 (ANI): A new gene therapy approach can reverse hearing loss caused by a genetic defect in a mouse model of congenital deafness, a new study has revealed.

Link:

Gene therapy shows promise in reversing congenital hearing loss