BreakThrough Digest Medical News |
- Targeted gene therapy enhances treatment for Pompe disease
- Experimental drug helps diabetes patients lose weight
- New hormonal gel combination shows promise as reversible birth control for men
- Gut microbes battle a common set of viruses shared by global populations
- Experimental insulin drug prevents low blood sugar
| Targeted gene therapy enhances treatment for Pompe disease Posted: 24 Jun 2012 09:00 PM PDT Gene 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. ### 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. Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 www.liebertpub.com |
| Experimental drug helps diabetes patients lose weight Posted: 24 Jun 2012 09:00 PM PDT An experimental drug helped significantly more overweight patients with diabetes shed pounds, compared with placebo, a new study finds. The results will be presented Saturday at The Endocrine Society’s 94th Annual Meeting in Houston.
“This new medication is promising because of the amount of weight loss it produces, the resultant improvement in important risk factors for diabetes, and, particularly in the lower dose studied, in its tolerability,” said study lead author Donna H. Ryan, M.D., professor emeritus at Pennington Biomedical Research Center (LSU System) in Baton Rouge, LA. Diabetes treatment involves weight management and medications to control blood-sugar levels and risk factors. If left untreated, diabetes can increase the danger of developing heart and blood-vessel diseases. Since one of the main risk factors for all of these diseases is obesity, weight loss is important to both prevention and treatment. Focusing on type 2 diabetes, investigators found that patients who took the experimental weight-loss drug phentermine/topiramate, combined with diet and exercise modifications, were more likely to lose moderate amounts of weight than those who received a sugar-pill placebo and the diet and exercise intervention. The percentage of study participants losing more than 10 percent of their initial weight while decreasing their blood pressure and hemoglobin A1c, was:
Phentermine/topiramate is a combined medication that works by decreasing appetite. The main side effects associated with the drug were constipation and tingling sensations in the fingers. Patients who took phentermine/topiramate were also more likely to develop low blood sugar than those who received placebo. This study was an analysis of diabetic patients who enrolled in weight-loss studies testing medications given with lifestyle intervention. Investigators randomly assigned 357 patients with type 2 diabetes to receive either low-dose phentermine/topiramate (7.5 milligrams), high-dose phentermine/topiramate (15 milligrams), or placebo. Neither investigators nor patients knew who was receiving the drug versus placebo in the double-blinded study. Participants’ average age was 53 years, 66 percent were female, most were white, and their average weight was 222 pounds. Follow-up was one year. ### VIVUS, the company that developed phentermine/topiramate, funded the study. Contact: Aaron Lohr |
| New hormonal gel combination shows promise as reversible birth control for men Posted: 24 Jun 2012 09:00 PM PDT
Male hormonal contraceptives applied daily to the skin reduce sperm production, finds a new study to be presented Sunday at The Endocrine Society’s 94th Annual Meeting in Houston. Very low sperm counts resulted for about 89 percent of men using a new combination of hormones, the authors reported. They combined a transdermal (skin) gel containing the male hormone testosterone and a gel containing a new synthetic progestin called Nestorone.
“This is the first time that testosterone and Nestorone have been applied to the skin together to deliver adequate amounts of hormones that suppress sperm production,” said principal investigator Christine Wang, MD, professor, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed). “Men can use transdermal gels at home?unlike the usual injections and implants, which must be given in a health care provider’s office.” Prior studies of male contraceptives that combined testosterone and progestin used progestin pills, implants or shots, according to Wang. In men, progestin increases the contraceptive effectiveness of testosterone. Both testosterone and progestin work together to turn off production of reproductive hormones controlling the production of sperm, she said. Furthermore, Wang said, unlike other progestins studied as male contraceptives, Nestorone has no androgenic (male hormone) activity. Androgenic activity may cause side effects such as acne and changes in good and bad cholesterol. In this preliminary study, the investigators randomly assigned 99 healthy men to use one of three unidentified transdermal treatments every day for six months. The assigned treatment was either a gel containing 10 grams of testosterone plus a placebo (“dummy”) gel, or the same testosterone gel plus a gel containing either 8 or 12 milligrams (mg) of Nestorone. Fifty-six men completed at least 20 weeks of treatment and adhered to the study protocol, according to the abstract. Only 23 percent of men who received testosterone alone obtained a sperm concentration less than 1 million sperm per milliliter, “a level that is compatible with very low pregnancy rates,” Wang said. For the testosterone-progestin combinations, sperm counts reached that level in 88 to 89 percent of men, depending on the progestin dose. In addition, complete absence of sperm occurred in significantly more men receiving combined testosterone and progestin than testosterone alone: 78 and 69 percent (8 and 12 mg of progestin, respectively) versus 23 percent for testosterone only. “The combination of testosterone with Nestorone had few adverse effects,” Wang said. “It warrants further study as a male contraceptive.” Nestorone is an investigational new drug being developed by the Population Council, a nonprofit organization in New York City, which supplied this drug for the study. Besins Pharma provided the testosterone gel. Grant funding came from the National Institute of Child Health and Human Development through the Contraceptive Clinical Trials Network. The University of Washington, Seattle, also participated in this study. Contact: Aaron Lohr |
| Gut microbes battle a common set of viruses shared by global populations Posted: 23 Jun 2012 09:00 PM PDT The human gut is home to a teeming ecosystem of microbes that is intimately involved in both human health and disease. But while the gut microbiota is interacting with our body, they are also under constant attack from viruses. In a study published online in Genome Research, researchers have analyzed a bacterial immune system, revealing a common set of viruses associated with gut microbiota in global populations.
Viruses that prey on bacteria, called phages, pose a constant threat to the health of bacterial communities. In many ecological systems, viruses outnumber bacterial cells ten to one. Given the richness of bacteria in the human gut, it was not surprising that scientists have found that phages are also highly prevalent. But how can viruses targeting gut microbiota be identified? How do viral communities differ between people and global populations, and what could this tell us about human health and disease? In this report, a team of scientists from Israel has taken advantage of information coded in a bacterial immune system to shed new light on these questions. Bacteria can “steal” small pieces of DNA from phages that attack them, and use these stolen pieces to recognize and respond to the attacker, in a manner similar to usage of antibodies by the human immune system. The stolen DNA pieces are stored in specific places in the bacterial genome called CRISPR loci (clustered regularly interspaced short palindromic repeats). “In our study we searched for such stolen phage DNA pieces carried by bacteria living in the human gut,” said Rotem Sorek of the Weizmann Institute of Science and senior author of the study. “We then used these pieces to identify DNA of phages that co-exist with the bacteria in the gut.” Sorek’s team used this strategy to identify and analyze phages present in the gut microbiota of a cohort of European individuals. They found that nearly 80% of the phages are shared between two or more individuals. The team compared their data to samples previously derived from American and Japanese individuals, finding phages from their European data set also present in these geographically distant populations, a surprising result given the diversity of phages seen in other ecological niches. Sorek explained that their findings mean that there are hundreds of types of viruses that repeatedly infect our gut microbiota. “These viruses can kill some of our gut bacteria,” said Sorek. “It is therefore likely that these viruses can influence human health.” The authors note that as evidence for the beneficial roles played by bacteria in the healthy human gut continues to mount, it is critical that we understand the pressures placed upon the “good” bacteria that are vital to human health. “Our discovery of a large set of phages attacking these good bacteria in our gut opens a window for understanding how they affect human health,” Sorek added. Researchers can now begin to ask how phage dynamics in the gut changes over time, and what it might tell us about diseases, such as inflammatory bowel disease, and how to more effectively treat them. Scientists from the Weizmann Institute of Science (Rehovot, Israel) and Tel Aviv University (Tel Aviv, Israel) contributed to this study. ### This work was supported by the ERC-StG Program, the Leona M. and Harry B. Helmsley Charitable Trust, the Deutsche Forschungsgemeinschaft, the AXA Research Fund, the Edmond J. Safra Bioinformatics Program at Tel Aviv University, and the Clore Center at the Weizmann Institute of Science. Media contacts: The authors are available for more information by contacting Yivsam Azgad, Institute Spokesman and Head of Publications & Media Relations at the Weizmann Institute of Science (yivsam.azgad@weizmann.ac.il, + 972 8 934 3856). Interested reporters may obtain copies of the manuscript via email from Peggy Calicchia, Administrative Assistant, Genome Research (calicchi@cshl.edu, +1-516-422-4012). About the article: The manuscript will be published online ahead of print on June 25, 2012. Its full citation is as follows: Stern A, Mick E, Tirosh I, Sagy O, Sorek R. CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome. Genome Res doi: 10.1101/gr.138297.112. About Genome Research:
Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies. About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory’s five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public. Genome Research issues press releases to highlight significant research studies that are published in the journal. Contact: Peggy Calicchia |
| Experimental insulin drug prevents low blood sugar Posted: 23 Jun 2012 09:00 PM PDT An experimental insulin drug prevented low blood sugar among diabetic patients more often than a popular drug on the market, a new study finds. The results will be presented Sunday at The Endocrine Society’s 94th Annual Meeting in Houston.
Nearly 26 million people in the United States have diabetes, which can cause blood sugar, or glucose, to climb to dangerously high levels. While treatment with the hormone insulin can help control blood sugar, it sometimes leads to abnormally low levels, or hypoglycemia. Symptoms of low blood sugar include headaches, tremors, and even seizures, so it is critical to develop medications that control blood sugar without causing extreme drops. “Diabetes is an increasingly common disease, and many patients fail to achieve their treatment goals due to a fear of hypoglycemia,” said lead investigator Daniel Einhorn, M.D., medical director at Scripps Whittier Diabetes Institute, and clinical professor of medicine at the University of California San Diego. “This puts them at risk of developing diabetes complications.” While both medications in this large-scale analysis decreased blood-sugar concentrations, the experimental drug, degludec, caused fewer incidents of low blood sugar, especially at night-time, compared to glargine. Overall, low blood-sugar levels occurred 14 percent less often among degludec patients than among those receiving glargine, also known as Lantus. At night, low blood sugar occurred 37 percent less often among degludec than glargine recipients. Sixteen weeks after the study, degludec patients had even fewer incidents of low blood sugar. During this maintenance period, the condition occurred 21 percent less frequently, overall, and 43 percent less often at night. No major complications were reported. “This study suggests that blood glucose can be effectively lowered by degludec, with a lower risk for hypoglycemia compared to currently available insulins,” Einhorn said. “It is therefore possible that treatment with degludec can improve patient outcomes by limiting the side effects associated with insulin use.” Investigators analyzed data from seven separate clinical trials. Two of these trials focused on type 1 diabetes, in which the body produces insufficient insulin to control blood-sugar levels. The other five trials examined the most common form of diabetes, known as type 2, in which the body both responds inadequately to insulin and produces inadequate amounts of the hormone. More than 3,000 participants were randomly assigned to receive either degludec or glargine once a day for 26 or 52 weeks. Of the total number, 2,899 patients received degludec, and 1,431 were given glargine. Nearly half of all patients on both drugs achieved targeted levels of blood-sugar control. While the investigators are presenting this study for the first time, results from the previous seven trials were previously publicized. Novo Nordisk, the maker of degludec, funded the study. Contact: Aaron Lohr ### |
| You are subscribed to email updates from BreakThrough Digest Medical News To stop receiving these emails, you may unsubscribe now. | Email delivery powered by Google |
| Google Inc., 20 West Kinzie, Chicago IL USA 60610 | |
