Treaty. Children with progeria brandish trophies after completing 2 years of a clinical trial for lonafarnib now reported to prolong the lifespan.
The Progeria Foundation
in 1998, toddler son Leslie Gordon Sam was diagnosed with an extremely rare and always fatal disease, progeria syndrome Hutchinson-Gilford, much like premature aging. Immediately, Gordon, a doctor, decided to do everything possible to change the sad prospect of the disease, the average age of death is 13: She gained a doctorate and formed a foundation that has allocated millions for research on progeria. This week, Gordon co-authors of a publication that describes the first clinical trial of a drug for progeria. She is optimistic that the drug helped children, including Sam, who participated. But others say that the results are difficult to interpret and it is not known therapy made a difference.
Hutchinson-Gilford progeria syndrome is caused by a spontaneous mutation in the design of a known gene LMNA , which codes for a protein called prelamin A. Progeria patients experience an accumulation of an abnormal version of prelamin a in their cells that, among other changes, deforms the nucleus and modifies gene expression. Although they appear normal at birth, toddlers with progeria do not develop properly, and as seniors, they begin to lose hair and body fat, and suffer stiffness and atherosclerosis . In 05, a group led by Stephen Young, a cardiologist at the University of California, Los Angeles, showed that a class of drugs called farnesyl transferase inhibitors (FTI) appeared to normalize the cells with progeria, and in 06, his team reported similar success in the disease mouse model.
The Progeria Research Foundation Gordon launched a test called an FTI lonafarnib, which had been tested without success in cancer. Twenty-five children-who account for 75% of those who are known to have the disease worldwide when the trial began, were followed closely for at least 2 years on lonafarnib. To measure success, the researchers focused on weight gain, which in children with progeria is progressing at a snail's pace. In the trial, nine children had an average weight gain of 0.52 kg per year, slightly more than a pound, an improvement over virtually no weight gain the previous year. The other 16 children had either no significant change in their rate of weight gain or lost weight during the study. The results were published online today in the Proceedings of the National Academy of Sciences .
Gordon is excited not only weight gain, but also by arterial stiffening measures evaluated in 18 children. In all but one, improved measurement, suggesting the ship had become more flexible and potentially reduce the risk of heart attacks and strokes. "We can change anything on the cardiovascular system has implications for health," said Gordon.
Others are not so sure. "I'm afraid we interpret the sound" in the data, rather than seeing real evidence of benefits, says Harry Dietz, a pediatric cardiologist at Johns Hopkins University in Baltimore, Maryland. "It is a complex document and hard to interpret, in my opinion," agrees Nicolas Lévy , molecular genetics director at the Children Hospital of Timone in Marseille, France, who helped lead a group that identified the gene mutation behind progeria in 03.
lonafarnib test research Foundation Progeria ended in 2010, but the base is now monitoring 45 children from 24 countries who take drugs and cholesterol drugs pravastatin and zoledronate, which prevents fractures. The two cells in a treated standardized progeria flat and mice with a version of the disease. Levy and his colleagues are now conducting a separate trial, testing the last two drugs on 12 children with progeria. They hope to present their findings soon.
An expanded version of this story appears in the September 28 issue of Science.
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