New method of predicting drug side effects could limit need for experimentation
SAN DIEGO A new method that searches an enormous database of protein structures could allow researchers to predict a drug’s potential side effects without researchers having to perform a single lab experiment, according to technologyreview.com.
Drugs work by latching onto very specific receptor sites on protein targets, like a key fitting into a lock. If a drug also happens to latch onto another, unintended target, it may produce unwanted side effects. The new method analyzes the shape of the intended lock and then combs through the structures of other proteins to look for similarly shaped locks. If such a lock is found, an algorithm rigorously determines whether the drug fits snugly into it. If it does, the technique has probably identified what’s called an “off-target.”
The researchers, led by University of California, San Diego pharmacologist Philip Bourne, didn’t stop there. Once they had identified an off-target, they worked backward, looking for other drugs known to bind to it and then using their technique to determine whether those drugs could also bind to the original target. If so, the researchers had further evidence that the two proteins—the intended target and the unintended target—had highly similar drug receptor sites. Then, by assessing the biological function of the off-target, they could suggest possible side effects of the drug being tested.
Bourne’s new technique reverses the approach ordinarily taken to computational drug design. Most methods focus on the drug rather than on the protein that it binds to. Pharmaceutical researchers routinely sift through databases of small molecules looking for drugs to match a particular protein. Bourne’s team, by contrast, is looking for proteins to match a particular drug.
The technique could also be used to identify ways to repurpose existing drugs, an application that Bourne’s group is currently exploring. Not all side effects are bad: just as the antidepressant bupropion, the active ingredient in Wellbutrin, is also used as an aid in smoking cessation, many drugs could have more than one beneficial use. Computational screening for off-targets could identify such alternative uses of known drugs.
New Jersey adds flu vaccine to list of childhood innoculations
PHILADELPHIA The state of New Jersey announced that, starting in September 2008, children entering day care or preschool will be required to have had flu vaccinations, despite some parents’ fears that the trace amounts of mercury in the vaccines could trigger autism.
The flu vaccine is an addition to the list of communicable diseases for which children in the state already are required to have before they can enter such social settings as day care or preschool, both situations in which contagious diseases are easily spread. “This is a public-health policy that is aimed at protecting children and the community at large,” Eddy Bresnitz, state epidemiologist and a deputy health commissioner, told the Philadelphia Inquirer.
Some parents, however, have expressed concern and even written letters to the Public Health Council in opposition to the change, mainly over safety concerns. While no scientific studies have found a link between thimerosal—a mercury-containing preservative once used in vaccines—and the triggering of autism in young children, some vaccines still contain trace amounts of the chemical and it’s enough to alarm parents.
“It is our feeling that parents have the right to make medical decisions for their families,” Sue Collins, a parent and leader of the New Jersey Alliance for Informed Choice in Vaccination, told the paper. “I don’t want trace amounts of mercury in my body or my children’s bodies under any circumstances. We know it is a dangerous toxin and yet we keep injecting it into our kids.”
“Thimerosol-free preparations are available, and the trace amounts in some preparations are truly tiny, tiny, tiny, tiny, tiny, tiny, tiny amounts,” said Craig Newschaffer, chair of the department of epidemiology and biostatistics at the Drexel University School of Public Health.
The new rules follow recommendations of the American Academy of Pediatrics and the U.S. Centers for Disease Control and Prevention.
New Jersey does allow exemptions based on medical and religious grounds, but not for “philosophical” reasons. “Flu is turning out to be a stealth killer,” said Robert Field, chair of the department of health policy and public health at the University of the Sciences in Philadelphia. “Seasonal flu, which most people can shrug off as an inconvenience for a week or two, is truly a threat to people at high risk, particularly the very old, the very young, and those with compromised immune systems.”
Tibotec awards Medivir $24 million for drug development milestone
STOCKHOLM, Sweden Medivir has received $24.54 million from Tibotec related to the development of the drug candidate TMC435350, which recently advanced into Phase II clinical trials at the end of November, according to published reports.
The money has come in two different payments. The first payment was for a clinical milestone reached by Medivir under the terms of the research and license agreement between the two companies; that amounted in $7.21 million for Medivir. The second payment is due because Medivir opted not to obtain the marketing rights to an approved product in the Nordic countries, which resulted in $17.32 million.
“Our goal is to achieve revenues from sales of licensed pharmaceuticals in the Nordic market in the coming 12 months,” explains Medivir’s chief executive officer Lars Adlersson. “A robust financial position will facilitate the creation of a Nordic sales and marketing organization and strengthen us in coming partnership negotiations.”