Saddled With Setbacks, Gene Therapy Finally Looking Up
The field of gene therapy experimentation has suffered a few notable setbacks recently, including the highly publicized death of one man in a Pennsylvania clinical trial. Although scientists have not yet conclusively determined that the man’s death was the result of the gene research, there have been other problems.
The goal of gene therapy is to replace a defective gene with a healthy one that will produce a missing protein. But researchers have struggled to get large enough quantities of the gene into a patient’s cells and then to induce the genes to produce enough protein to improve the patient’s health. The most common way to introduce new genes is to insert them into a virus--one that has been defanged so it doesn’t produce disease--that will introduce them into cells. But these viruses can produce an immune reaction such as the one that killed 18-year-old Jesse Gelsinger.
Last week, however, researchers from Children’s Hospital of Philadelphia and the Stanford University Medical Center presented some good news for a change. In preliminary results from a safety trial of a new system for treating hemophilia B, they found not only that the virus they used does no harm, but that it was providing substantial benefits to the patients.
Hemophilia B is caused by a deficiency of a protein called factor IX. Without factor IX, blood does not clot properly, and a victim can bleed to death from a small cut. Recombinant factor IX produced by genetic engineering techniques can stimulate clotting, but it is expensive and must be injected. Gene therapy could provide a more permanent solution.
The researchers used an adeno-associated virus (AAV) developed by Avigen Inc. of Alameda, Calif., as the “vector” to introduce the factor IX gene. AAV is a common virus that has been shown to be present in most humans and that, most important, does not produce an immune reaction.
Dr. Katherine High of Children’s Hospital reported at a New Orleans meeting of the American Society of Hematology that the team had injected a low dose of AAV into the muscle of three hemophilia B patients. None showed a reaction to the virus, and all three began producing factor IX, thereby reducing their need for recombinant factor IX. The production persisted for the six months that the patients were monitored. They now give higher doses to the next group of patients.
If Morning Sickness Is Extreme, It May Be a Girl
Women who suffer from extreme nausea and vomiting during the first three months of pregnancy are more likely to be carrying a girl than a boy, according to Swedish researchers. The condition is called hyperemesis gravidarum and may be related to increased production of a pregnancy-related hormone called human chorionic gonadotropin.
Dr. Johan Askling and his colleagues at the Karolinska Institutet in Stockholm studied all Swedish births from 1987 to 1995, a total of more than 1 million. They reported in Saturday’s Lancet that the overall male-to-female ratio was 51.4 to 48.6. Among women hospitalized for hyperemesis gravidarum, however, the ratio was 44.3 to 55.7.
St. John’s Wort Beneficial in Depression Treatment
St. John’s wort, a popular over-the-counter herbal remedy, is as effective in treating depression as the common anxiety drug imipramine, German scientists report.
The team reported in Saturday’s British Medical Journal that imipramine and hypericum extract--the active ingredient in St. John’s wort--were equally effective and both were more effective than a placebo. The findings are the most recent in a series of studies showing that St. John’s wort has beneficial properties.
Although imipramine has been displaced by some of the newer, Prozac-like drugs called selective serotonin reuptake inhibitors, it is still considered the gold standard against which new treatments for depression are evaluated.
Dr. Karl-O. Hiller of the Steiner Arzneimittel in Berlin and his colleagues studied 263 patients with moderate depression. One-third were given 350 milligrams of hypericum extract three times daily, one-third were given 100 milligrams of imipramine once daily and the rest received a placebo.
Side effects were similar in all groups. Because many depression patients receive inadequate treatment or none at all, the authors concluded that hypericum extract may be considered as an alternative first choice in treatment of mild to moderate depression.
Zinc Reduces Childhood Pneumonia, Diarrhea
Widespread use of zinc supplements could prevent millions of cases of pneumonia and diarrhea among children in developing nations, according to a new study in the December Journal of Paediatrics. Researchers from the World Health Organization and the Johns Hopkins School of Hygiene and Public Health combined the findings from 10 small studies of the efficacy of zinc supplements to reach their conclusion.
They calculated that the supplements could reduce the incidence of diarrhea by as much as 25% and that of pneumonia by about 41%. The effect on diarrhea prevention compares favorably with interventions like clean water and breast-feeding, while zinc has a greater preventive effect on pneumonia than any current intervention. Pneumonia and diarrhea are among the leading causes of childhood death in developing nations.
Doctors Asked to Stop Oral Polio Vaccine Use
The American Academy of Pediatrics is recommending that physicians abandon the oral polio vaccine for routine childhood vaccinations and use only injected killed-virus vaccine. Most physicians now use a combination of the two types in a series of vaccinations, and the current recommendation is that the killed-virus vaccine be used first.
The problem with the oral vaccine, which uses a weakened form of the polio virus, is that a small number of children who receive it each year develop polio. Its advantage is that it produces immunity faster.
The new guidelines, published in the December Pediatrics, would allow physicians to use up their remaining supplies of the oral vaccine before switching to the killed-virus product exclusively.
Mortality at Record Low, Life Span Highest in 1998
The U.S. death rate reached its lowest point ever last year and life expectancy hit an all-time high, according to another report in the December Pediatrics. Researchers from the Johns Hopkins School of Hygiene and Public Health said the death rate in 1998 was 470.8 per 100,000 population. Average life expectancy reached 76.7 years, an increase of 0.2% from the previous year. AIDS deaths were down 21%; from homicide, down 14% and from suicide, down 6%. Live births rose 2%, the first increase since 1990. Infant mortality was 7.2 deaths for every 1,000 live births, equaling the previous year’s record low.
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Medical writer Thomas H. Maugh II can be reached by e-mail at thomas.maugh@latimes.com.
