Health
A research team in Israel has devised a novel approach to identifying the molecular basis for designing a drug that might one day decrease the risk diabetes patients face of developing Alzheimer's disease.
The team presented its work at the 57th annual meeting of the Biophysical Society, held Feb. 2-6 in Philadelphia, Pa.
A recent study suggests that people who suffer from type 2 diabetes face twice the risk of developing Alzheimer's disease later in life compared to those who do not have diabetes.
The link these diseases share relates to the formation of two types of peptide deposits that aggregate, or clump together.
Peptides are chains of amino acids; longer chains form proteins. One type of peptide, called amyloid beta, is found in Alzheimer plaques in neurons of the brain. The other type, amylin, is found in the pancreas and the brain.
Two years ago, researchers found both molecules in the pancreas of diabetic patients, and in both diseases their presence has been linked to the progression of the disease state.
To explore the hypothesis that interactions between the two molecules might play a critical role in the self-assembly of peptides that leads to protein aggregation, Yifat Miller, assistant professor from Ben-Gurion University of the Negev, Beer-Sheva, Israel, characterized the way the two protein molecules interact with each other through an examination of their structure. It was the first analysis of its kind.
“By identifying the specific 'hot regions' of these peptides that strongly interact with each other, our study may provide insight into the link between type 2 diabetes and Alzheimer's disease,” Miller said. “We believe that preventing these interactions by developing a drug will decrease the risk that type 2 diabetes patients face of developing Alzheimer's disease later life.”
Collaborator Aphrodite Kapurniotu of Technische Universität München, Freising-Weihenstephan, Germany, performed the molecular experimental examination of the interactions between these two peptides. Miller's research received funding from the European Union Seventh Framework Programme.
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Three clinical trials that seek to find more effective treatments for influenza are enrolling volunteers with influenza at the National Institutes of Health’s Clinical Center in Bethesda, Md., and at several dozen other domestic and international sites.
One study examines whether treatment with a licensed influenza drug, oseltamivir, reduces the time that infected people continue to produce virus in the upper airway.
A second tests whether a combination of three licensed flu antiviral drugs works better than oseltamivir alone in people with influenza who have chronic health conditions, such as heart or lung disease, that put them at greater risk of severe illness.
The third tests whether treatment with plasma enriched with anti-influenza antibodies improves the condition of hospitalized influenza patients compared to standard antiviral treatment alone.
“This year’s flu season came earlier than usual and has been particularly hard on the elderly,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious diseases, part of the NIH. “Despite our best efforts to prevent influenza through vaccination, people still get sick every year with the flu. At best, influenza infection is a miserable experience. At worst, it can be a deadly one. We need better ways to treat people with influenza, which kills thousands of people in the United States each year, and clinical research supported by NIAID helps to address that need.”
The studies are sponsored by the NIAID Influenza Research Collaboration, a clinical research network funded by the NIAID Division of Clinical Research (DCR). Researchers at 36 sites in the United States and additional sites in Argentina, Australia, Mexico and Thailand participate.
Activities of the collaboration are coordinated under the leadership of Richard Davey, M.D., deputy clinical director, NIAID DCR, and John Beigel, M.D., medical affairs scientist on contract with NIAID.
Although oseltamivir has been approved for use in the United States since 1999, no studies have shown conclusively whether the drug significantly reduces the amount of virus produced (shed) by an infected person. Reduced shedding would likely lessen the chances of an infected person passing the virus to others.
The oseltamivir trial will enroll a total of approximately 560 people at 31 locations in the United States, Argentina and Thailand.
Enrollees must be between the ages of 18 and 65 years and have confirmed influenza virus infection but not be hospitalized or suffering from any other health conditions that would put them at risk of developing influenza complications.
The trial comparing oral oseltamivir alone to treatment with oseltamivir plus two other licensed antiviral drugs is enrolling a total of up to 720 adults at sites in the United States, Argentina, Australia, Mexico and Thailand.
In addition to having laboratory-confirmed influenza, enrollees must have at least one other characteristic that places them at higher risk of developing serious complications. Asthma and other lung disorders, heart disease, obesity, weakened immune function and being over age 65 are some of the conditions that place people at higher risk for serious disease.
The third trial is enrolling children as well as adults, including pregnant women, hospitalized with severe influenza.
This trial aims to enroll a total of approximately 100 people at approximately 20 sites in the United States.
All participants will receive standard drug treatment for influenza, and half will also receive two infusions of plasma enriched with antibodies against the virus. Antibodies are infection-fighting proteins produced by the immune system.
The antibodies used in the trial are derived from blood donated by volunteers who were recently vaccinated against flu or are recovered from a recent bout of flu.
“Anecdotal evidence suggests that the addition of plasma with high levels of antibody against the virus may confer additional benefit over drug treatment alone. This trial will be one of the first to examine that possibility in a scientifically rigorous fashion,” said Dr. Davey. “The outcome of this trial may provide valuable data on how best to treat patients hospitalized with severe influenza.”
Detailed information about each of the trials now enrolling volunteers is also available at http://www.clinicaltrials.gov .
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