BreakThrough Digest Medical News |
- Discovery of immune cells that protect against multiple sclerosis offers hope for new treatment
- Turmeric spices up virus study
- Combination peptide therapies might offer more effective, less toxic cancer treatment
| Discovery of immune cells that protect against multiple sclerosis offers hope for new treatment Posted: 15 Aug 2012 09:00 PM PDT In multiple sclerosis, the immune system attacks nerves in the brain and spinal cord, causing movement problems, muscle weakness and loss of vision. Immune cells called dendritic cells, which were previously thought to contribute to the onset and development of multiple sclerosis, actually protect against the disease in a mouse model, according to a study published by Cell Press in the August issue of the journal Immunity. These new insights change our fundamental understanding of the origins of multiple sclerosis and could lead to the development of more effective treatments for the disease.
“By transfusing dendritic cells into the blood, it may be possible to reduce autoimmunity,” says senior study author Ari Waisman of University Medical Center of Johannes Gutenberg University Mainz. “Beyond multiple sclerosis, I can easily imagine that this approach could be applied to other autoimmune diseases, such as inflammatory bowel disease and psoriasis.” In an animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE), immune cells called T cells trigger the disease after being activated by other immune cells called antigen-presenting cells (APCs). Dendritic cells are APCs capable of activating T cells, but it was not known whether dendritic cells are the APCs that induce EAE. In the new study, Waisman and his team used genetic methods to deplete dendritic cells in mice. Unexpectedly, these mice were still susceptible to EAE and developed worse autoimmune responses and disease clinical scores, suggesting that dendritic cells are not required to induce EAE and other APCs stimulate T cells to trigger the disease. The researchers also found that dendritic cells reduce the responsiveness of T cells and lower susceptibility to EAE by increasing the expression of PD-1 receptors on T cells. “Removing dendritic cells tips the balance toward T cell-mediated autoimmunity,” says study author Nir Yogev of University Medical Center of Johannes Gutenberg University Mainz. “Our findings suggest that dendritic cells keep immunity under check, so transferring dendritic cells to patients with multiple sclerosis could cure defects in T cells and serve as an effective intervention for the disease.” ### Yogev et al.: “Dendritic Cells Ameliorate Autoimmunity in the CNS by Controlling the Homeostasis of PD-1 Receptor+ Regulatory T Cells.” Contact: Lisa Lyons |
| Turmeric spices up virus study Posted: 15 Aug 2012 09:00 PM PDT
The popular spice turmeric packs more than just flavor ? it shows promise in fighting devastating viruses, Mason researchers recently discovered. Curcumin, found in turmeric, stopped the potentially deadly Rift Valley Fever virus from multiplying in infected cells, says Aarthi Narayanan, lead investigator on the new study and a research assistant professor with Mason’s National Center for Biodefense and Infectious Diseases.
Mosquito-borne Rift Valley Fever virus (RVF) is an acute, fever-causing virus that affects domestic animals such as cattle, sheep and goats, as well as humans. The research appears this month in the Journal of Biological Chemistry. “Growing up in India, I was given turmeric all the time,” says Narayanan, who has spent the past 18 months working on the project. “Every time my son has a throat infection, I give (turmeric) to him.” There’s more work to do before curcumin-based pharmaceuticals become commonplace, Narayanan emphasizes. She plans to test 10 different versions of curcumin to determine which one works the best. She also intends to apply the research to other viruses, including HIV. Narayanan has long wanted to explore the infection-fighting properties of turmeric, in particular its key component, curcumin. “It is often not taken seriously because it’s a spice,” she says. But science is transforming the spice from folk medicine to one that could help a patient’s body fight off a virus because it can prevent the virus from taking over healthy cells. These “broad-spectrum inhibitors” work by defeating a wide array of viruses. “Curcumin is, by its very nature, broad spectrum,” Narayanan says. “However, in the published article, we provide evidence that curcumin may interfere with how the virus manipulates the human cell to stop the cell from responding to the infection.” Kylene Kehn-Hall, a co-investigator on the study, adds, “We are very excited about this work, as curcumin not only dramatically inhibits RVFV replication in cell culture but also demonstrates efficacy against RVFV in a mouse model.” Narayanan and her colleagues study the connection between a virus and how it impacts the host ? human or animal. Symptoms clue in the researcher about the body’s inner workings. Rift Valley Fever and Venezuelan Equine Encephalitis kick off with flu-like symptoms. Symptoms can make it challenging for someone to recover. The body usually starts with an exaggerated inflammatory response because it doesn’t know where to start to rid itself of the virus, she says. “Many times, the body goes above and beyond what is necessary,” Narayanan says. “And that’s not good because it’s going to influence a bunch of cells around the infection, which haven’t seen the bug. That’s one way by which disease spreads through your body. And so it is very important to control the host because a lot of times the way the host responds contributes to the disease.” Controlling the symptoms means more than simply making the patients feels better. “You’re giving the antiviral a chance to work. Now an antiviral can go in and stop the bug. You’re no longer trying to keep the host alive and battling the bug at the same time.” Once Narayanan knows how the body responds to a virus, it’s time to go after the bug itself. She’s applying this know-how to a family of viruses called Bunyaviruses, which feature Rift Valley fever, and such alphaviruses as Venezuelan equine encephalitis and retroviruses, which notably include HIV. She delves into uncovering why and how each virus affects the patient. “Why are some cell types are more susceptible to one type of infection than another?” HIV goes after the immune system. Bunyaviruses will infect a wide range of cells but do maximum damage to the liver. “What is it about the liver that makes it a sitting duck compared to something like the brain?” Narayanan asks. Ultimately, curcumin could be part of drug therapies that help defeat these viruses, Narayanan says. “I know this works. I know it works because I have seen it happen in real life,” Narayanan says. “I eat it every day. I make it a point of adding it to vegetables I cook. Every single day.” ### Other Mason researchers involved in the study are Charles Bailey, Ravi Das, Irene Guendel, Lindsay Hall, Fatah Kashanchi, Svetlana Senina and Rachel Van Duyne. Several researchers from other institutions also collaborated. About George Mason University
George Mason University is an innovative, entrepreneurial institution with global distinction in a range of academic fields. Located in Northern Virginia near Washington, D.C., Mason provides students access to diverse cultural experiences and the most sought-after internships and employers in the country. Mason offers strong undergraduate and graduate degree programs in education, engineering and information technology, organizational psychology, health care and visual and performing arts. With Mason professors conducting groundbreaking research in areas such as climate change, public policy and the biosciences, George Mason University is a leading example of the modern, public university. George Mason University?Where Innovation Is Tradition. Contact: Michele McDonald |
| Combination peptide therapies might offer more effective, less toxic cancer treatment Posted: 15 Aug 2012 09:00 PM PDT
Two studies suggest that two peptide agents used either together or individually with a low-dose of a standard chemotherapy drug might offer more effective cancer therapy than current standard single-drug treatments. The studies used animal models of breast cancer to show that the peptide combinations dramatically delay tumor onset and progression by both inhibiting tumor growth and blocking the formation of new tumor blood vessels, say the researchers at the Ohio State University Comprehensive Cancer Center ? Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC ? James) who conducted the study. In addition, the treatments caused few side effects. The findings are described in two papers published online in the journal OncoImmunology. The first paper describes how vaccination with a HER2 peptide followed by treatment with a VEGF peptide inhibitor prevents tumor formation in a transplantable mammary tumor model. The second paper documents how either HER2 peptide or VEGF peptide treatment combined with low-dose paclitaxel effectively kills tumor cells in both the transplantable tumor model and a transgenic mammary tumor model. “For treating cancer, combination therapies are much more effective than individual therapies, and peptides in combination, whether by vaccination or as therapy, appear to be safer, nontoxic, and taking us closer to a cure,” says principle investigator Dr. Pravin Kaumaya, director of the division of vaccine development at the OSUCCC ? James. Kaumaya, who is a professor of obstetrics and gynecology, of molecular and cellular biochemistry, and of microbiology at Ohio State, led the research that developed the peptide agents. Peptides are short chains of amino acids, and the HER2 peptide and VEGF peptide are short amino-acid chains that mimic full-length HER2 and VEGF molecules. The HER2 receptor molecule is important for controlling tumor growth in many cancers; the VEGF receptor molecule controls the formation of new blood vessels needed to feed tumors. Both molecules are overexpressed in many cancers. In the new studies, the researchers investigated whether the peptide vaccine and the peptide inhibitor worked more effectively in combination, and also whether they could synergize with a standard chemotherapy agent, paclitaxel. The HER2 peptide vaccine is injected into the body where it causes the immune system to generate antibodies to the HER2 receptor. These antibodies then bind to the overexpressed HER2 receptors on cancer cells, preventing them from stimulating tumor-cell proliferation. The VEGF therapeutic peptide binds directly to the VEGF receptor molecule, preventing it from directing the formation of new blood vessels. In the first paper, the team shows that vaccinating mice with the HER2 peptide before aggressive mammary cancer cells are transplanted into the mice can delay the onset of the tumors. When this vaccination treatment was combined with weekly treatments of the VEGF peptide, tumor growth was significantly delayed. In animals given the VEGF peptide, which is engineered not to break down in the body, 40 percent of the animals did not develop tumors at all by the end of the experiment. In theory, Kaumaya explains, such a peptide vaccine could prevent HER2-driven breast cancer from developing in a daughter who inherited the genetic risk for this cancer from her mother. “We could vaccinate a person who doesn’t have the cancer and create a memory for HER2 overexpression in her immune system,” he says. “Then, when a tumor starts growing and over-expressing HER2, it would crank up her immune system to produce antibodies to shut the cancer down.” This study’s results suggest that adding VEGF peptide therapy might halt tumor progression altogether. The second paper lays groundwork for testing peptide therapies in clinical trials. These experiments tested whether the HER2 peptide vaccine or the VEGF peptide therapy would boost the effectiveness of paclitaxel, a standard chemotherapy drug, when the drug is used at low dose to reduce its toxicity. “We know from other people’s work that treating patients with a low-dose chemotherapy agent like paclitaxel primes the system to be more responsive to other targeted treatments,” Kaumaya says. Indeed, the team showed that both peptide treatments used individually with paclitaxel delayed tumor growth and development and produced better response rates than either agent without the drug in both transplanted and transgenic mouse breast cancer models. Importantly, the combined therapies showed no toxic side effects. In contrast, paclitaxel and the current standard anti-HER2 therapy, trastuzumab, both had toxic effects on the heart. “Our goal is to find a cure by interfering with various cancer-cell pathways using medicines that are not toxic,” Kaumaya says. ### Other Ohio State researchers involved in the two studies were Kevin Foy, Megan Miller, Nicanor Moldovan, Tatjana Bozanovic, and William E. Carson, III. The Ohio State University Comprehensive Cancer Center ? Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S. News & World Report. Contact: Darrell E. Ward |
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