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| Genetic editing shows promise in Duchenne muscular dystrophy Posted: 03 Jun 2013 09:00 PM PDT Using a novel genetic ‘editing’ technique, Duke University biomedical engineers have been able to repair a defect responsible for one of the most common inherited disorders, Duchenne muscular dystrophy, in cell samples from Duchenne patients.
Instead of the common gene therapy approach of adding new genetic material to “override” the faulty gene, the Duke scientists have developed a way to change the existing mutated gene responsible for the disorder into a normally functioning gene. The Duke researchers believe their approach could be safer and more stable than current methods of gene therapy. The researchers are now conducting further tests of this new approach in animal models of the disease. Duchenne muscular dystrophy is a genetic disease affecting one in 3,600 newborn males. The genetic mutation is found on the X chromosome, of which males have only one copy. (Females, with two X chromosomes, presumably have at least one good copy of the gene.) Patients with Duchenne muscular dystrophy cannot produce the protein known as dystrophin, which is essential in maintaining the structural integrity of muscle fibers. Over time, patients with the disorder suffer gradual muscle deterioration, which leads to paralysis and eventual death, usually by age 25. “Conventional genetic approaches to treating the disease involve adding normal genes to compensate for the mutated genes,” said Charles Gersbach, assistant professor of biomedical engineering at Duke’s Pratt School of Engineering and Department of Orthopaedic Surgery and member of Duke’s Institute for Genome Sciences and Policy. “However, this can cause other unforeseen problems, or the beneficial effect does not always last very long. “Our approach actually repairs the faulty gene, which is a lot simpler,” said David Ousterout, the Duke biomedical engineering graduate student in the Gersbach lab who led the work. “It finds the faulty gene, and fixes it so it can start producing a functional protein again.” The results of the Duke study were published online in Molecular Therapy, the journal of the American Society for Gene and Cell Therapy. The project was supported by the Hartwell Foundation, the March of Dimes Foundation and the National Institutes of Health. The Duke experiments, which were carried out in cell samples from Duchenne muscular dystrophy patients, were made possible by using a new technology for building synthetic proteins known as transcription activator-like effector nucleases (TALENs), which are artificial enzymes that can be engineered to bind to and modify almost any gene sequence. These TALENs bind to the defective gene, and can correct the mutation to create a normally functioning gene. “There is currently no effective treatment for this disease,” Gersbach said. “Patients usually are in a wheelchair by the age of ten and many die in their late teens or early twenties.” Duchenne muscular dystrophy has been extensively studied by scientists, and it is believed that more than 60 percent of patients with this type of mutation can be treated with this novel genetic approach. “Previous studies indicate that restoring the production of dystrophin proteins will be highly functional and alleviate disease symptoms when expressed in skeletal muscle tissue,” said Ousterout. Similar approaches could be helpful in treating other genetic diseases where a few gene mutations are responsible, such as sickle cell disease, hemophilia, or other muscular dystrophies, Gersbach said. ### Other members of the team were Duke’s Pablo Perez-Pinera, Pratiksha Thakore, Ami Kabadi, Matthew Brown, Xiaoxia Qin, and Olivier Fedrigo. Other participants were Vincent Mouly, Universite Pierre at Marie Curie, Paris, and Jacques Tremblay, Universite Laval, Quebec. Citation: “Reading frame correction by targeted genome editing restores dystrophin expression in cells from Duchenne muscular dystrophy patients,” David Ousterout, et. al, Molecular Therapy, DOI 10.1038/mt.2013.111. Contact: Richard Merritt |
| Study finds taking probiotics has benefits for patients in hospitals Posted: 03 Jun 2013 09:00 PM PDT
Patients in hospital who are on antibiotics may benefit from taking probiotics, according to researchers at St. Michael’s Hospital. Dr. Reena Pattani led a literature review that looked at the effectiveness of probiotics, live bacteria that can take up residence in digestive tracts, in treating common side effects of antibiotics, such as antibiotic-associated diarrhea and life-threatening side effects such as Clostridium difficile infection.
?These two conditions are associated with high morbidity, mortality and health care costs,? said Dr. Pattani, an internal medicine resident. ?Antibiotics are non-specific ? they target both our good and bad bacteria. And some of the good bacteria being killed off protect us from pathogens like C. difficle, a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the body.? Previous studies have shown 10 per cent of patients who receive antibiotics while in hospital will get antibiotic-associated diarrhea and of these patients, 15 per cent of them will have diarrhea because of C. difficle. Dr. Pattani and colleagues scanned available literature for studies that compared patients who received probiotics and antibiotics at the same time in hospital, with patients who received antibiotics alone to see if rates of antibiotic-associated diarrhea and C. difficle infection were lower in those who also received probiotics. They pooled the results of 16 studies, looking at data from 3,403 patients, and found a significant reduction in both antibiotic-associated diarrhea and C. difficle infection in patients who took probiotics with their antibiotics. The results are likely due to the powerful effects of probiotics, including their ability to populate the digestive tract with healthy bacteria and strengthen the immune system, Dr. Pattani said. ?Hospitalization is a key risk factor for acquiring C. difficle infection,? Dr. Pattani said. ?Probiotics can help improve the health of individual patients by preventing C. difficle while also reducing the transmission of C. difficle to other, non-infected people in the high-risk inpatient environment. We hope these results will prompt physicians to consider its use.? Dr. Pattani said that while the results of her study are encouraging, a larger study including more patients, and one that looks at what kind of probiotics work best and at what doses needs to be done before hospital-wide policies can be made. The paper appeared online in the journal Open Medicine today. Dr. Pattani is a resident at the University of Toronto and St. Michael?s incoming chief resident. ### About St. Michael?s Hospital
St Michael?s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 23 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital?s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael?s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. For more information or to speak to Dr. Pattani please contact: Kate Taylor Leslie Shepherd |
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