In 2003, scientists described the complete genetic script that underlies the biology of humans. This genetic information is in the form of chemical letters; in total, it comprises a book that contains 3 billion characters.
One of the important findings from these advances in genetics is that a “typo” in even one of those letters can result in a serious, even deadly, genetic disease. Identifying and correcting these errors is one of the key goals of research in this field. Scientists have been successful in identifying these mistakes in a number of diseases, including muscular dystrophy, sickle cell anemia and the subject of this article, progeria.
Progeria is a very rare condition — only about 33 children are currently known to be living with the disease. Its key characteristic is premature aging. Starting after the first year of life, children with progeria appear to age quickly — they lose their hair, begin to lose weight, have vision deficits and develop joint problems. Children with progeria typically die from a heart attack or stroke in their early teens.
In hopes that an understanding of progeria could lead to treatments for the disease and potentially a better understanding of natural aging, scientists tracked down the cause of the disease — a typo in just one of the 3,000,000,000 letters in the human genome. This gene normally is involved in manufacturing a protective shell around the cell’s nucleus, the “brain” of the cell. Because of the error in the gene, the malformation of this molecular “skull” distorts the nucleus, and this ultimately leads to premature death of cells throughout the body. This cell death, in turn, causes the various aging symptoms in individuals with the disease.
The identification of the genetic error that caused progeria helped clarify possible targets for drug therapy. Fortunately, scientists had already developed some potential drugs that homed in on these targets as possible anti-cancer therapies. These drugs were initially tested on cells from progeria patients in the laboratory, and in mice that mimic the disease. In both cases, the drugs appeared to be effective in mitigating the genetic defect. So researchers, including a mother of a child with progeria, conducted a clinical trial to investigate the potential benefit of one of these drugs.
There were a number of challenges in setting up the trial. For one thing, since so few children are afflicted with progeria, the number of individuals in the trial would be very small. Normally, clinical trials have a control group, which receives a sugar pill, and an experimental group, which actually gets the drug. Because of the limited number of participants, it was decided that all of them would receive the drug. The children were monitored for two years, and tracked for weight gain and other physical changes.
The results of the trial were not entirely clear; some of the children gained weight, some lost weight, and some saw no change. Some of the children also had other physical changes suggestive of improvement in their condition, and some did not. Although this trial did not provide a cure for individuals with progeria, it shows the potential of new genetic technology to allow rapid progress in understanding inherited diseases and identifying potential treatments. The pace of these discoveries is likely to accelerate in coming years with a better understanding and new genetic tools.
More information is available in:
E Leslie Gordon and others, “Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome.” Proceedings of the National Academy of Sciences, USA Sept. 24, 2012, www.pnas.org/cgi/doi/10.1073
E Jennifer Couzin-Frankel. “Drug trial offers uncertain start in race to save children with progeria.” Science 337:1594-1595, Sept. 28, 2012.
PATRICK GUILFOILE has a Ph.D. in bacteriology and is currently an interim associate vice president at Bemidji State University.