BreakThrough Digest Medical News |
- A vaccine for heart disease? La Jolla Institute discovery points up this possibility
- Researchers aim to grow salivary glands using patient’s own cells
- Scientists devise new strategy to destroy multiple myeloma
- An artificial retina with the capacity to restore normal vision
| A vaccine for heart disease? La Jolla Institute discovery points up this possibility Posted: 13 Aug 2012 09:00 PM PDT Most people probably know that heart disease remains the nation’s No. 1 killer. But what many may be surprised to learn is that cholesterol has a major accomplice in causing dangerous arterial plaque buildup that can trigger a heart attack. The culprit? Inflammatory cells produced by the immune system.
A number of research studies have demonstrated inflammation’s role in fueling plaque buildup, also known as atherosclerosis, which is the underlying cause of most heart attacks and strokes, but knowledge of which immune cells are key to this process has been limited ? until now. Researchers at the La Jolla Institute for Allergy & Immunology have identified the specific type of immune cells (CD4 T cells) that orchestrate the inflammatory attack on the artery wall. Further, the researchers discovered that these immune cells behave as if they have previously seen the antigen that causes them to launch the attack. “The thing that excites me most about this finding is that these immune cells appear to have ‘memory’ of the molecule brought forth by the antigen-presenting cells,” said Klaus Ley, M.D., a renowned expert in vascular immunology, who led the study in mouse models. “Immune memory is the underlying basis of successful vaccines. This means that conceptually it becomes possible to consider the development of a vaccine for heart disease.” Dr. Ley said he believes the antigen involved is actually a normal protein that the body mistakes as being foreign and therefore launches an immune attack resulting in inflammation in the arteries. “Essentially, we’re saying that there appears to be a strong autoimmune component in heart disease,” he said, explaining that autoimmune diseases result from the body’s mistaken attack on normal cells. “Consequently, we could explore creating a “tolerogenic” vaccine, such as those now being explored in diabetes, which could induce tolerance by the body of this self-protein to stop the inflammatory attack.” The study was published online Monday in the Journal of Clinical Investigation in a paper entitled “Dynamic T cell?APC interactions sustain chronic inflammation in atherosclerosis.” Dr. Ley cautions that creating a vaccine is a complex process that could take years to develop. However it offers exciting potential. “If successful, a tolerogenic vaccine could stop the inflammation component of heart disease,” he said. “This could probably be used in conjunction with the statins (cholesterol-lowering drugs) that have already taken a significant chunk out of the numbers of people with heart disease. Together, they could deliver a nice one-two punch that could be important in further reducing heart disease.” Dr. Ley said antigen-presenting cells take up infectious organisms, foreign materials and self-proteins (in the case of autoimmune diseases) and “chop them into little pieces called epitopes” and then display the pieces on the surface of the cell. “The T cell comes along, and if it has the correct receptors, it will recognize the epitope pieces and make cytokines (a type of immune system soldier molecule) that attack the material and cause inflammation.” Autoimmune diseases include such illnesses as type 1 diabetes, rheumatoid arthritis and multiple sclerosis. In the study, Dr. Ley and his team used live cell imaging techniques to track immune cells in normal and artherosclerotic mouse aortas. He said in mice with atherosclerosis, there are a large number of antigen-experienced T cells that have already seen certain epitope pieces (from self proteins) that they perceive as foreign. “The T cells talk to the antigen-presenting cells and, in response, make cytokines that launch an attack. This is what makes the inflammation in the vessel wall persistent.” Inflammatory cells join fat and cholesterol to form artery-clogging plaque that can eventually block blood flow, leading to a heart attack. “It wasn’t previously known that antigen-experienced T cells existed in the vessel wall,” said Dr. Ley. “This experiment makes me now believe that it may be possible to build a vaccine for heart disease.” ### About La Jolla Institute
Founded in 1988, the La Jolla Institute for Allergy & Immunology is a biomedical research nonprofit focused on improving human health through increased understanding of the immune system. Its scientists carry out research seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious diseases, cancer, inflammatory and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes, Crohn’s disease and asthma. La Jolla Institute’s research staff includes more than 150 Ph.D.s and M.D.s. To learn more about the Institute’s work, visit www.liai.org. Contact: Bonnie Ward |
| Researchers aim to grow salivary glands using patient’s own cells Posted: 13 Aug 2012 09:00 PM PDT
Biologists, surgical oncologists and regenerative medicine specialists from Rice University, the University of Delaware and the Christiana Care Health System in Wilmington, Del., have begun a four-year program aimed at using cells to grow whole salivary glands that can replace those destroyed by cancer radiation therapy.
The research, which is funded by a $2.5 million grant from the National Institutes of Health’s National Institute of Dental and Craniofacial Research, could benefit thousands of cancer patients who suffer from xerostomia, or dry mouth. Dry mouth is an especially severe problem for patients with cancers of the head and neck because the mouth’s saliva-producing acinar cells are particularly susceptible to radiation. As a result, about 40,000 head and neck cancer patients who undergo standard radiation therapy each year report serious problems with dry mouth. The condition can make it painful for patients to swallow, eat and even speak. It also causes accelerated tooth decay and oral infections. “We’ve already shown that we can harvest acinar cells prior to radiation therapy, grow them in the lab, implant them into test animals and maintain their ability to produce salivary enzymes,” said Cindy Farach-Carson, Rice’s Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology and the principal investigator on the new grant. “In the next phase of the research, we want to show that we can make whole salivary glands that can integrate into the host and increase saliva production. To do that, we need more than just saliva-producing cells. We need nerves and ducts and blood vessels and all the other things that make up the gland itself.” If the research is successful, it could pave the way for future clinical trials. Farach-Carson, a biologist and longtime cancer researcher, said the regenerative salivary gland project is possible only because the research team includes experts in cell biology, clinical oncology and tissue engineering. For example, Rice’s project team includes co-investigator Daniel Harrington, faculty fellow in biochemistry and cell biology, who has expertise in polymer science and materials engineering. Farach-Carson, who also serves as Rice’s vice provost for translational bioscience and as scientific director of Rice’s BioScience Research Collaborative, spends a good deal of her time extolling the benefits of research that crosses disciplinary and institutional boundaries. She said the salivary gland project is a perfect example of what can happen when experts from disparate fields come together to solve a common problem. “This all began in 2005 when I went on sabbatical and was randomly assigned to share an office with Robert Witt, one of Delaware’s leading head and neck surgical oncologists,” Farach-Carson said. “My prior work had been with prostate cancer, so Bob and I traded stories about our previous work and found some common ground. Around that time, we also met Xinqiao Jia, a materials scientist at the University of Delaware who specializes in creating biomaterials for regenerative medicine.” Witt, who directs the Head and Neck Multidisciplinary Center at Christiana Care’s Helen F. Graham Cancer Center, said, “There is currently no way to prevent or cure xerostomia for cancer patients who are undergoing radiation therapy. This is clearly a problem where regenerative medicine holds great promise for improving the quality of life for many people.” In addition, the research could also benefit those with Sjögren’s syndrome, a chronic disease in which a person’s immune system attacks the body’s moisture-producing glands. Up to 4 million Americans live with Sjögren’s syndrome. Jia, associate professor of materials science and engineering, said recreating the structure and function of whole salivary glands is a challenge. “Every tissue in the body has unique requirements from its surroundings,” she said. “The biocompatible polymers we create at the University of Delaware can be tuned to match the structure of soft tissues in salivary glands. We can also incorporate specific biological cues to direct the growth and organization of the cells that are seeded into the polymers.” Jia said her group works closely with their biological and clinical partners to identify the key properties that must be incorporated into the hydrogel polymers to direct cell organization and growth. “This partnership over the past seven years has been incredibly rewarding for all of us,” Farach-Carson said. “Generous support from a patient of Dr. Witt provided the initial resources that enabled our early studies and brought us to where we are now. Without that help, we might never have reached this major milestone today.” ### A high-resolution image is available for download at: http://news.rice.edu/wp-content/uploads/2012/08/0810_SALIVA_image1-hg.jpg CAPTION: Surgical oncologists and engineers from Delaware meet weekly by videoconference with Rice University researchers Daniel Harrington and Cindy Farach-Carson to discuss their efforts to grow whole salivary glands to replace those destroyed by cancer radiation therapy. A high-resolution image is available for download at: http://news.rice.edu/wp-content/uploads/2012/08/0810_SALIVA_image2-lg.jpg CAPTION: Researchers have shown that salivary cells cultured outside the body can be coaxed into forming organized structures similar to those found in the body. These images show cells marked with fluorescent dyes that identify specific proteins found in salivary tissues. A copy of the NIH grant abstract is available at: http://projectreporter.nih.gov/project_info_details.cfm?aid=8390897&icde=13217123 Follow Rice News and Media Relations via Twitter @RiceUNews Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,708 undergraduates and 2,374 graduate students, Rice’s undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice has been ranked No. 1 for best quality of life multiple times by the Princeton Review and No. 4 for “best value” among private universities by Kiplinger’s Personal Finance. To read “What they’re saying about Rice,” go to www.rice.edu/nationalmedia/Rice.pdf. Contact: David Ruth |
| Scientists devise new strategy to destroy multiple myeloma Posted: 13 Aug 2012 09:00 PM PDT Researchers at Virginia Commonwealth University Massey Cancer Center are reporting promising results from laboratory and animal experiments involving a new combination therapy for multiple myeloma, the second most common form of blood cancer.
The study published online in the journal Cancer Research details a dramatic increase in multiple myeloma cell death caused by a combination of the drugs obatoclax and flavopiridol. The researchers, led by Steven Grant, M.D., Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, program co-leader and member of Developmental Therapeutics and member of the Cancer Cell Signaling program at VCU Massey Cancer Center, found that the two drugs worked together through different mechanisms to promote a form of cell suicide known as apoptosis. “There is an urgent need for curative therapies for multiple myeloma,” says Grant. “Our hope is that this research will lay the foundation for new and more effective treatments for patients with multiple myeloma and potentially other blood cancers for which adequate therapies are lacking.” Obatoclax is an experimental agent currently being investigated in various forms of blood cancers. It works by disabling proteins that prevent cancer cells from undergoing apoptosis. Flavopiridol is a member of a class of agents known as a cyclin-dependant kinase (CDK) inhibitors, and blocks the growth of cancer cells in addition to reducing levels of anti-apoptotic proteins. In laboratory experiments, the novel drug combination dramatically increased multiple myeloma cell death. These results were confirmed in animal models where the drugs significantly improved the survival of immune-compromised mice with human multiple myeloma. An unexpected effect was also observed ? flavopiridol, in addition to reducing levels of anti-apoptotic proteins, significantly increased the expression of apoptosis-inducing proteins such as Bim, a protein shown in previous studies to trigger cell death. “This research builds on nearly a decade of work carried out by our laboratory that focuses on manipulating mechanisms that lead to apoptosis in hematological malignancies,” says Grant. “Our findings could have immediate implications for the design of clinical trials using combinations of these types of drugs. In fact, plans to develop such a trial at Massey are currently underway.” Because the findings showed synergism between these two classes of drugs, the researchers plan to test other clinically-relevant CDK inhibitors in combination with obatoclax for multiple myeloma. ### Grant collaborated with the study’s lead co-authors, Yun Dai, M.D., Ph.D., and Shuang Chen, M.D., Ph.D., from the VCU Department of Internal Medicine, who were key contributors to this work. Other collaborators included Xinyan Pei, M.D., Ph.D., also from the VCU Department of Internal Medicine; Paul Dent, Ph.D., Universal Corporation distinguished professor in cancer cell signaling and member of the Developmental Therapeutics program at VCU Massey; and Robert Orlowski, Ph.D., M.D., from M.D. Anderson Cancer Center. The full manuscript of this study can be found at: http://cancerres.aacrjournals.org/content/early/2012/06/14/0008-5472.CAN-12-1118.long This research was supported by NIH Research Project Grant (RO1) CA100866, a Multiple Myeloma SPORE award from the National Cancer Institute, the Multiple Myeloma Research Foundation, the Leukemia and Lymphoma Society of America and, in part, by funding from VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059. News directors: Broadcast access to VCU Massey Cancer Center experts is available through VideoLink ReadyCam. ReadyCam transmits video and audio via fiber optics through a system that is routed to your newsroom. To schedule a live or taped interview, contact John Wallace, (804) 628-1550. About VCU Massey Cancer Center
VCU Massey Cancer Center is one of only 67 National Cancer Institute-designated institutions in the country that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It has one of the largest offerings of clinical trials in Virginia and serves patients in Richmond and in five satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at www.massey.vcu.edu or call 877-4-MASSEY for more information. About VCU and the VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls more than 32,000 students in 211 certificate and degree programs in the arts, sciences and humanities. Sixty-nine of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu. Contact: John Wallace |
| An artificial retina with the capacity to restore normal vision Posted: 13 Aug 2012 09:00 PM PDT Two researchers at Weill Cornell Medical College have deciphered a mouse’s retina’s neural code and coupled this information to a novel prosthetic device to restore sight to blind mice. The researchers say they have also cracked the code for a monkey retina ? which is essentially identical to that of a human ?and hope to quickly design and test a device that blind humans can use.
The breakthrough, reported in the Proceedings of the National Academy of Sciences (PNAS), signals a remarkable advance in longstanding efforts to restore vision. Current prosthetics provide blind users with spots and edges of light to help them navigate. This novel device provides the code to restore normal vision. The code is so accurate that it can allow facial features to be discerned and allow animals to track moving images. The lead researcher, Dr. Sheila Nirenberg, a computational neuroscientist at Weill Cornell, envisions a day when the blind can choose to wear a visor, similar to the one used on the television show Star Trek. The visor’s camera will take in light and use a computer chip to turn it into a code that the brain can translate into an image. “It’s an exciting time. We can make blind mouse retinas see, and we’re moving as fast as we can to do the same in humans,” says Dr. Nirenberg, a professor in the Department of Physiology and Biophysics and in the Institute for Computational Biomedicine at Weill Cornell. The study’s co-author is Dr. Chethan Pandarinath, who was a graduate student with Dr. Nirenberg and is currently a postdoctoral researcher at Stanford University. This new approach provides hope for the 25 million people worldwide who suffer from blindness due to diseases of the retina. Because drug therapies help only a small fraction of this population, prosthetic devices are their best option for future sight. “This is the first prosthetic that has the potential to provide normal or near-normal vision because it incorporates the code,” Dr. Nirenberg explains. Discovering the Code
Normal vision occurs when light falls on photoreceptors in the surface of the retina. The retinal circuitry then processes the signals from the photoreceptors and converts them into a code of neural impulses. These impulses are then sent up to the brain by the retina’s output cells, called ganglion cells. The brain understands this code of neural pulses and can translate it into meaningful images. Blindness is often caused by diseases of the retina that kill the photoreceptors and destroy the associated circuitry, but typically, in these diseases, the retina’s output cells are spared. Current prosthetics generally work by driving these surviving cells. Electrodes are implanted into a blind patient’s eye, and they stimulate the ganglion cells with current. But this only produces rough visual fields. Many groups are working to improve performance by placing more stimulators into the patient’s eye. The hope is that with more stimulators, more ganglion cells in the damaged tissue will be activated, and image quality will improve. Other research teams are testing use of light-sensitive proteins as an alternate way to stimulate the cells. These proteins are introduced into the retina by gene therapy. Once in the eye, they can target many ganglion cells at once. But Dr. Nirenberg points out that there’s another critical factor. “Not only is it necessary to stimulate large numbers of cells, but they also have to be stimulated with the right code ? the code the retina normally uses to communicate with the brain.” This is what the authors discovered ? and what they incorporated into a novel prosthetic system. Dr. Nirenberg reasoned that any pattern of light falling on to the retina had to be converted into a general code ? a set of equations ? that turns light patterns into patterns of electrical pulses. “People have been trying to find the code that does this for simple stimuli, but we knew it had to be generalizable, so that it could work for anything ? faces, landscapes, anything that a person sees,” Dr. Nirenberg says. Vision = Chip Plus Gene Therapy
In a eureka moment, while working on the code for a different reason, Dr. Nirenberg realized that what she was doing could be directly applied to a prosthetic. She and her student, Dr. Pandarinath, immediately went to work on it. They implemented the mathematical equations on a “chip” and combined it with a mini-projector. The chip, which she calls the “encoder” converts images that come into the eye into streams of electrical impulses, and the mini-projector then converts the electrical impulses into light impulses. These light pulses then drive the light-sensitive proteins, which have been put in the ganglion cells, to send the code on up to the brain. The entire approach was tested on the mouse. The researchers built two prosthetic systems ? one with the code and one without. “Incorporating the code had a dramatic impact,” Dr. Nirenberg says. “It jumped the system’s performance up to near-normal levels ? that is, there was enough information in the system’s output to reconstruct images of faces, animals ? basically anything we attempted.” In a rigorous series of experiments, the researchers found that the patterns produced by the blind retinas in mice closely matched those produced by normal mouse retinas. “The reason this system works is two-fold,” Dr. Nirenberg says. “The encoder ? the set of equations ? is able to mimic retinal transformations for a broad range of stimuli, including natural scenes, and thus produce normal patterns of electrical pulses, and the stimulator (the light sensitive protein) is able to send those pulses on up to the brain.” “What these findings show is that the critical ingredients for building a highly-effective retinal prosthetic ? the retina’s code and a high resolution stimulating method ? are now, to a large extent, in place,” reports Dr. Nirenberg. Dr. Nirenberg says her retinal prosthetic will need to undergo human clinical trials, especially to test safety of the gene therapy component, which delivers the light?sensitive protein. But she anticipates it will be safe since similar gene therapy vectors have been successfully tested for other retinal diseases. “This has all been thrilling,” Dr. Nirenberg says. “I can’t wait to get started on bringing this approach to patients.” ### The study was funded by grants from the National Institutes of Health and Cornell University’s Institute for Computational Biomedicine. Both Drs. Nirenberg and Pandarinath have a patent application for the prosthetic system filed through Cornell University. Weill Cornell Medical College Weill Cornell Medical College, Cornell University’s medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances ? including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson’s disease, and most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu. Contact: Lauren Woods |
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