June 2006
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Research
Pictured here is a popular Chinese herbal prescription for so-called "wind-related conditions," including stroke. Patients boil each ingredient for specified amounts of time to make a tea. Sucher estimates that this single prescription contains 250 or more chemical compounds.
Stroke and epilepsy: East meets West
Traditional Chinese herbal medicine has been practiced for millennia, yet has rarely been rigorously tested like Western medicine. Nikolaus Sucher, MD, PhD, in Children's Hospital Boston's Division of Neuroscience, is one of a handful of U.S. scientists who are probing Chinese herbal medicines at the molecular level, with the hope of someday developing better Western-style treatments for stroke and epilepsy.Focusing on 58 traditional Chinese medicines used to treat stroke, Sucher used a variety of techniques to determine what ingredients they contain—a complicated task, since ingredients can vary and aren't always detectable by usual laboratory methods. Sucher showed that many herbal formulations are active at molecular targets known to be important in both stroke and epilepsy. Whole formulations often showed more activity than single compounds within them.
"My major insight was that you can't just isolate active compounds into a drug," Sucher says. "Rather, you have to go with a combination approach."
Chinese herbal formulations contain, on average, six to seven different drugs: a so-called "ruler," or principal ingredient, directed at a disease's main cause and symptoms, "minister" drugs directed at underlying causes and their symptoms, "assistants" to target secondary symptoms and counteract side effects of the other drugs and "enablers" to direct the drugs' action into the right "channels." But in the United States, combination therapies are uncommon, and the FDA forbids clinical trials of drug combinations except for conditions like cancer and HIV.
Sucher's studies, summarized in the March issue of Epilepsy & Behavior, also found that many compounds act on multiple targets, and bind to those targets only weakly. Qualities like these are typically shunned by U.S. pharmaceutical companies, which favor "magic bullets"—single drugs with single targets to which they bind tightly.
But with the drug pipeline running dry, the industry is starting to take a second look at natural products—the source of drugs like aspirin, digitalis and penicillin—in hopes of finding novel compounds. Expanded treatment options, whether single drugs or combinations, would greatly benefit children and adults with epilepsy and stroke.
Research briefs
This year's Pediatric Academic Societies meeting included nearly 100 presentations from Children's Hospital Boston. Below are just a few of the studies presented. For more, visit: www.childrenshospital.org/newsroom.Injury prevention by zip code
When it comes to childhood injury, not all zip codes are equal, finds a study led by Eric Fleegler, MD, MPH, in Children's Division of Emergency Medicine. Using 2002 data, Fleegler and colleagues mapped the nearly 200,000 Massachusetts hospital visits for pediatric injury to their zip code of origin. Of 503 zip-code areas, 39 zip codes accounted for 30 percent of all hospital charges for pediatric injury. Fleegler believes the map will help target scant injury-prevention dollars.ADHD drugs can stunt children's growth
Stimulants like Ritalin and Adderall have been the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) for the last 40 years. Now, an analysis of 22 selected trials finds that children on these drugs have slightly restricted growth, averaging about three-quarters of an inch in height for a 10-year-old boy. The researchers, including Children's Omar Khwaja, MD, and Dean Sarco, MD, in Neurology, suggest close growth monitoring for children taking ADHD drugs.Validating an obesity gene
Genes that cause obesity are extremely hard to pin down: obesity likely involves many different genes and numerous outside factors, but a recent study linked obesity with a common variant of a gene called INSIG2. Now,¬İChildren's researchers Helen Lyon, MD, MS, in Genomics and Genetics, and Joel Hirschhorn, MD, PhD, in Genomics, Genetics and Endocrinology, have helped to replicate the finding in five of six large, demographically diverse populations. A surprising 10 percent of the world's population carries two copies of the INSIG2 variant, making it a good possible starting point for developing obesity treatments.
