July 28, 2006, 10:20 PM CT

gene therapy for hereditary heart conditions

A new way of delivering corrective genes with a single injection into a vein holds promise for long-lasting treatments of hereditary diseases of the heart, University of Florida researchers report.

UF researchers used the approach to successfully reverse symptoms in mice with a form of muscular dystrophy that damages the heart. They also tested the virus-based delivery method in monkeys and found genes were readily absorbed by heart muscle cells, and the effect persisted for months.

The findings, published July 27 in the online edition of Circulation Research, pave the way for studies in humans that could begin as soon as early next year for patients with Pompe disease, a rare form of muscular dystrophy that is usually fatal in the first year of life.

"Nine years ago we knew we could get long-term gene expression in the heart but it was with direct injection into the heart muscle and it was inefficient," said UF pediatric cardiologist Barry J. Byrne, M.D., Ph.D., the paper's senior author and director of the Powell Gene Therapy Center. "The difference here is that we can deliver a much lower dose of the vector into a vein like any other drug, and the corrective gene collects in the heart".

Scientists say gene therapy looks increasingly feasible for the treatment of cardiovascular conditions linked to faulty genes or congenital metabolic diseases, including atherosclerosis, stroke, muscular dystrophy and an enlargement of the heart muscle known as dilated cardiomyopathy.........

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July 28, 2006, 9:32 PM CT

Nanotechnology And Atherosclerosis

In laboratory tests, one very low dose of a drug was enough to show an effect on notoriously tenacious artery-clogging plaques. What kind of drug is that potent?

It's not so much the drug itself as how it was delivered. Fumagillin - a drug that can inhibit the growth of new blood vessels that feed atherosclerotic plaques - was sent directly to the base of plaques by microscopically small spheres called nanoparticles developed by researchers at Washington University School of Medicine in St. Louis.

"Previously we reported that we can visualize plaques using our nanoparticle technology, but this is the first time we've demonstrated that the nanoparticles can also deliver a drug to a disease site in a living organism," says Patrick Winter, Ph.D., research assistant professor of medicine. "After a single dose in laboratory rabbits, fumagillin nanoparticles markedly reduced the growth of new blood vessels that feed plaques".

The researchers report their findings in the recent issue of the journal Arteriosclerosis, Thrombosis, and Vascular Biology, and the article is now available on line.

An atherosclerosis plaque results when a buildup of cholesterol, inflammatory cells and fibrous tissue forms inside an artery. If a plaque ruptures, it can block blood flow to the heart or brain, causing heart attack or stroke.........

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July 26, 2006, 5:29 PM CT

Human Behavior Changes Infectious Diseases

Simple models predict that only one strain of an infectious disease can exist at one time, but observation suggests otherwise. In a study in the recent issue of The American Naturalist, Ken Eames and Matt Keeling (University of Warwick) use a mathematical model to help explain multiple strains, showing that the way humans interact is all-important. The scientists observed that the coexistence of multiple infectious disease strains result from monogamous populations.

"When people are serially monogamous (that is, interactions take place one at a time), groups with different behavior favor strains with different properties," explain the authors. "When new interactions occur frequently, rapidly transmitted strains are most successful, but when new interactions take place infrequently there is extra pressure on strains to have a long infectious period".

Eames and Keeling focused their study on sexually transmitted infections, where the assumption of monogamy is most applicable, but stress that their conclusions may have wider relevance.

"There are implications for all sorts of other infections too," Eames continues. "Just think of the behavioral differences between village and city life: one with quiet streets and few new faces, and the other with thousands of hurrying people and crowded public transport. That's two very different environments for a pathogen. There are always going to be plenty of factors that determine which strains emerge, but human mixing behavior has a big part to play".........

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July 26, 2006, 4:50 PM CT

Keeping Babies From Deadly Infections

The Food and Drug Administration on Tuesday approved a new test studied at the University of Florida that could lead to better screening for the most common cause of infection in newborn babies.

Passed from mother to child during birth, group B streptococcus can cause sepsis, pneumonia, meningitis, neurological damage and, in a small percentage of newborns, even death.

Although all women are tested for group B streptococcus during pregnancy, current screening methods can leave some babies at risk for contracting an infection from the bacterium. But the new test, which UF researchers studied for several months as part of a clinical trial, allows health-care workers to quickly screen mothers during labor, improving the odds that babies will receive preventive care so they will not be infected during delivery.

"Without any intervention, (group B strep) is the most common cause of early-onset infection in newborns," said Rodney Edwards, M.D., a UF assistant professor of obstetrics and gynecology in the College of Medicine who led the clinical trial at UF, one of six sites to study the test. "It can cause sepsis, meningitis and pneumonia. The likelihood of dying if you are a newborn is 5 percent. (With meningitis) even if the baby makes it through the infection there is a chance of cerebral palsy and cognitive delay".........

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July 22, 2006, 10:45 PM CT

Watching Real-time Chemical Activity In Cells

Attempts to identify potential drugs that interfere with the action of one particular enzyme linked to heart disease and similar health problems led scientists at Johns Hopkins to create a new tool and new experimental approach that allow them to see multiple, real-time chemical reactions in living cells. Their report on the work is published July 21 in the journal ACS Chemical Biology.

Most current drug development operations test chemicals on enzymes isolated from their normal environs and then take further steps to see if the chemical can get into the cell to do its work, and figure out how poisonous the chemical is to a cell.

"Living cells are critical to our work because they show us how and what is actually happening in a normal context and time span when a chemical is added," says Jin Zhang, Ph.D., an assistant professor of pharmacology and molecular sciences in Hopkins' Institute for Basic Biomedical Sciences.

Testing chemicals on enzymes in living cells provides the opportunity to find potential drugs that work in new ways. For example, using living cells allows researchers to "see" where in the cell chemicals do their work. Scientists could then design new drugs to go to specific places within cells to work more efficiently. Also, streamlining the one-at-a-time approach offers the chance to study - and rule out or in - many potentially useful chemicals at once.........

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July 19, 2006, 10:31 PM CT

Breast Stem Cell Secrets

The most aggressive form of breast cancer may originate from breast stem cells that have undergone genetic mishaps.

Victorian Breast Cancer Research Consortium researchers from The Walter and Eliza Hall Institute, using mouse models, have discovered that breast stem cells do not express receptors for the female hormones oestrogen or progesterone. These and other features of the stem cell resemble the aggressive 'basal' subtype of breast cancer. There is increasing evidence that breast cancer is not simply a single disease. Researchers now view breast cancer as a heterogeneous disease, made up of various subtypes. This observation has led to speculation that breast tumours are derived from different cell types that could include the breast stem cell or its descendents that have suffered genetic accidents.

This possibility has generated great interest in understanding the composition of normal breast cells including the stem cell. A question of particular interest is whether the breast stem cell expresses receptors for oestrogen and progesterone and the marker 'Her2', since these help define the subtypes of breast cancer; and also guide current approaches to treatment.

The WEHI team, together with the Eaves group in Vancouver, have observed that the breast stem cell in mice is 'triple negative' for oestrogen, progesterone and Her2 receptors but does express certain 'basal cell' markers. These characteristics also define the basal subtype of breast cancer, which is more usually seen in tumours that develop in women who are carriers of the breast cancer predisposing gene BRCA1.........

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July 19, 2006, 10:04 PM CT

Autism: Fewer Neurons For Processing Emotion

For the first time, research has shown that the autistic brain has fewer neurons in an area related to emotion and social behavior, according to a new study published in the July 19 issue of The Journal of Neuroscience.

This study provides quantitative evidence linking autism to an abnormality of the amygdala, especially the lateral nucleus-a major emotion-processing area with connections to parts of the brain responsible for higher cognitive functions.

"These new findings, based on cell counting, complement other independent studies that suggest amygdala abnormalities likely contribute significantly to the primary core deficit in social function that defines this disorder," says Emanuel DiCicco-Bloom, MD, professor of pediatric neurology at the University of Medicine and Dentistry of New Jersey.

Authors Cynthia Schumann, PhD, of the University of California, San Diego, and David Amaral, PhD, director of the M.I.N.D. Institute at the University of California, Davis, counted and measured neurons in the amygdala of nine postmortem autistic male brains and 10 age-matched male postmortem non-autistic brains. Ages ranged from 10 to 44 years old. Unlike previous postmortem studies, the sample excluded brains of individuals with epilepsy or similar disorders associated with cell loss in the amygdala.........

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July 19, 2006, 6:16 AM CT

Improving Breast Cancer Diagnosis

New software created by FAU researchers and Boca Raton Community Hospital is set to improve breast cancer diagnosis. When used in combination with magnetic resonance imaging, this software gives a much better quality picture and makes it easier for the physicians to detect abnormalities among normal breast tissue seen in a mammogram or ultrasound.

For hard-to-diagnose cases, it could save a woman from a mastectomy by pinpointing the dimensions of a cancer and giving doctors the option of a lumpectomy.

It also could save a woman's life by finding cancers too small to show up in regular detection methods.

"There are many cases when you get a suspicious feeling from a mammography but you don't have a definitive diagnosis," said Roger Goldwyn, a mathematics professor at Florida Atlantic University who helped develop the new technology. "This enhanced MRI allows you to really determine what is there".

The software, technically called contrast enhanced dynamic imagining, is being used at Boca Raton Community Hospital's Center for Breast Care on high-risk patients and those recently diagnosed with breast cancer.

Although the Food and Drug Administration approved the software in 2004, officials are just now asking for $10 million in federal money to help continue the research and package the program to allow more hospitals to use it.........

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July 18, 2006, 9:05 PM CT

Distinguished Professor Of Ophthalmology

J. William Harbour, M.D., has been named the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences at Washington University School of Medicine in St. Louis.

Washington University Chancellor Mark S. Wrighton joined Larry J. Shapiro, M.D., executive vice chancellor for medical affairs and dean of the School of Medicine, in announcing the appointment.

"Endowed professorships are among the most important gifts a university can receive because they allow us to recognize outstanding individuals and to support their important contributions in research and education," Wrighton says. "In addition to supporting Dr. Harbour's current work, this distinguished chair also honors a seminal figure in Washington University's history".

"Dr. Paul Cibis was one of the true pioneers of modern vitreoretinal surgery, a remarkably gifted doctor and scientist," Shapiro says. "It is highly appropriate that a professorship endowed in his name help to support the work of Bill Harbour, a physician/scientist who is one of our most gifted eye surgeons".

The Cibis Distinguished Professorship was established in 2000 by a donor who wishes to remain anonymous. It honors the late Paul A. Cibis, M.D., an important figure in the history of Washington University's Department of Ophthalmology and Visual Sciences.........

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July 18, 2006, 8:36 PM CT

New diabetes drug may also cause weight reduction

The Washington University Diabetes Center at Barnes-Jewish Hospital focuses on providing patients with the latest technology, treatments and clinical research. Some patients at the center are receiving a new diabetes drug that may give a welcome side effect - weight loss.

Byetta, developed by Amylin Pharmaceuticals and Eli Lilly and Co., is designed to help patients with type 2 diabetes get better control of their condition by helping the body make more of its own insulin. The drug, a twice-daily injection, tells the pancreas to make the right amount of insulin after meals to bring blood sugar closer to normal levels. It also helps stop the liver from producing too much sugar when the body doesn't need it, and helps slow down the rate at which sugar enters the bloodstream. It is typically used along with oral diabetes medications, and in some patients, it has led to weight loss.

One of the patients taking Byetta is Cris Welling, a research lab supervisor in the endocrinology/metabolism lab of M. Alan Permutt, M.D., professor of medicine and of cell biology and physiology. About five years ago, Welling volunteered to be a non-diabetic control in a University research study. When she went through the initial tests, she found out she had pre-diabetes.

Welling's physician, Garry Tobin, M.D., associate professor of medicine and medical director of the diabetes center, had prescribed several other oral medications to treat her diabetes, but none helped her to lose weight. Since she began taking Byetta for type 2 diabetes about 10 months ago, she has lost about 40 pounds. She no longer needs medicine for high blood pressure and has reduced the medicine she takes for high cholesterol.........

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