BreakThrough Digest Medical News |
- Preventing cellular aging and aging-related degenerative diseases
- Anti-cocaine vaccine described in Human Gene Therapy Journal
- Discovery helps mice beat urinary tract infections
| Preventing cellular aging and aging-related degenerative diseases Posted: 17 Jun 2012 09:00 PM PDT Age-associated degeneration is caused, at least in part, by accumulated cellular damage, including DNA damage, but how these types of damage drive aging remains unclear. Dr. Paul Robbins and colleagues at the University of Pittsburgh sought to address this question using a mouse model of DNA repair deficiency. The Robbins team found that DNA damage drives aging, in part, by activating NF-?B, a transcription factor that responds to cellular damage and stress. They report that inhibition of NF-?B reduces oxidative stress, oxidative DNA damage, oxidative protein damage, and cellular senescence induced by oxidative damage. Their data suggest that NF-?B inhibitors can mitigate cellular damage and could provide clinical benefit for degenerative changes caused by aging. ### TITLE: NF-?B inhibition delays DNA damage?induced senescence and aging in micContact: Sarah Jackson |
| Anti-cocaine vaccine described in Human Gene Therapy Journal Posted: 17 Jun 2012 09:00 PM PDT
New Rochelle, NY, June 18, 2012?A single-dose vaccine capable of providing immunity against the effects of cocaine offers a novel and groundbreaking strategy for treating cocaine addiction is described in an article published Instant Online in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc. (http://www.liebertpub.com) The article is available free online at the Human Gene Therapy website (http://www.liebertpub.com/hum).
“This is a very novel approach for addressing the huge medical problem of cocaine addiction,” says James M. Wilson, MD, PhD, Editor-in-Chief, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia. In the article “AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior,” (http://online.liebertpub.com/doi/pdfplus/10.1089/hum.2011.178) a team of researchers from Weill Cornell Medical College (New York, NY), The Scripps Research Institute (La Jolla, CA), and Cornell University (Ithaca, NY) used a virus-based delivery vehicle in mice to transfer a gene that produces a protein capable of binding to cocaine present in the blood, preventing the cocaine from crossing into the brain. The protein is a monoclonal antibody that sequesters cocaine, making the vaccinated mice resistant to the drug’s effects. Whereas unvaccinated mice exhibited hyperactivity when exposed to intravenous cocaine, the immunized mice showed no effects, according to authors Jonathan Rosenberg, et al. ### About the Journal
Human Gene Therapy (http://www.liebertpub.com/hum), the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies is an authoritative peer-reviewed journal published monthly in print and online that presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Tables of contents and a free sample issue may be viewed online at the Human Gene Therapy website (http://www.liebertpub.com/hum). About the Publisher
Mary Ann Liebert, Inc. (http://www.liebertpub.com) is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 70 journals, books, and newsmagazines is available at the Mary Ann Liebert, Inc. website (http://www.liebertpub.com). Contact: Vicki Cohn |
| Discovery helps mice beat urinary tract infections Posted: 17 Jun 2012 09:00 PM PDT Scientists at Washington University School of Medicine in St. Louis have found new clues to why some urinary tract infections recur persistently after multiple rounds of treatment. Their research, conducted in mice, suggests that the bacteria that cause urinary tract infections take advantage of a cellular waste disposal system that normally helps fight invaders. In a counterintuitive finding, they learned that when the disposal system was disabled, the mice cleared urinary tract infections much more quickly and thoroughly.
“This could be the beginning of a paradigm shift in how we think about the relationship between this waste disposal system, known as autophagy, and disease-causing organisms,” says senior author Indira Mysorekar, PhD, assistant professor of obstetrics and gynecology and of pathology and immunology. “There may be other persistent pathogens that have found ways to exploit autophagy, and that information will be very useful for identifying new treatments.” The results will be published the week of June 18, 2012, in the early online edition of The Proceedings of the National Academy of the Sciences. Urinary tract infections are very common, particularly in women. In the United States alone, annual treatment costs are estimated to run as high as $1.6 billion. Scientists believe 80 percent to 90 percent of these infections are caused by the bacterium Escherichia coli (E. coli). Data from the new study and earlier results have led Mysorekar and her colleagues to speculate that E. coli that cause recurrent urinary tract infections may hide in garbage-bin-like compartments within the cells that line the urinary tract. These compartments, found in nearly all cells, are called autophagosomes. They sweep up debris within the cell, including harmful bacteria and worn-out cell parts. Then, they merge with other compartments in the cell that are filled with enzymes that break down the contents of autophagosomes. “We think, but can’t yet prove, that the bacteria have found a way to block this final step, ” Myosrekar says. “This would transform the autophagosome from a death trap into a safe haven where the bacteria can wait, hidden from the immune system, for their next chance to start an infection.” In the new research, Mysorekar teamed with colleagues at the School of Medicine who had developed mice in which both copies of an important autophagy gene, Atg16L1, were impaired. Co-author Herbert W. Virgin, MD, PhD, Edward Mallinckrodt Professor and head of the Department of Pathology and Immunology, and others created the mice to study Crohn’s disease, a chronic bowel inflammation associated with mutations in Atg16L1. Co-lead authors Caihong Wang, DVM, PhD, a staff scientist, and Jane Symington, an MD/PhD student in the Mysorekar group, infected the mice with E. coli. The researchers found that bacteria levels in the urinary tracts of the modified mice decreased much more rapidly after infection than they did in normal mice. Cells lining the urinary tract in mice with the mutated gene also had significantly fewer dormant reservoirs of E. coli than in normal mice. The scientists identified structural changes in urinary tract cells of the mice with Atg16L1 mutations that may help explain their unexpected results. These changes may have made it much more difficult for the bacteria to find and break into autophagosomes, Mysorekar says. The altered gene also was associated with changes in the immune system. In the modified mice, E. coli infections in the urinary tract led cells to produce more inflammatory immune factors and prompted additional bacteria-fighting immune cells to come to the site of the infection. “The immune system appears to be primed to attack at the slightest provocation in the mice with mutations,” Mysorekar says. “This may be why mutations in Atg16L1 are also connected with Crohn’s disease, which involves immune cells erroneously attacking beneficial microorganisms in the gut.” Mutations in Atg16L1 are quite common, according to Virgin, although not everyone who has a mutated form of the gene will get Crohn’s disease. “These new results may help explain why the mutations have persisted for so long in the general population,” he says. “They don’t just put the carrier at risk of Crohn’s disease, they also may have a protective effect that helps fight infections.” Mysorekar plans to investigate how E. coli takes advantage of a fully functioning autophagy system in mice with urinary tract infections. ### Wang C, Mendonsa GR, Symington JW, Zhang Q, Cadwell K, Virgin HW, Mysorekar IU. Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo. The Proceedings of the National Academy of Sciences, early online edition, week of June 18, 2012. Funding from National Institute of Child Health and Human Development Grant T32-54560 (to G.R.M.), U54AI057160, Project 5 (to H.W.V.) and K99/R00 Pathway to Independence Award DK080643 (to I.U.M.) supported this research. Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare. Contact: Michael C. Purdy |
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