A drug approved for the treatment of cancer and prevent rejection of transplanted organs can also help children with progeria, a disease that resembles accelerated aging and typically kills those who are afflicted by their teenagers-a new study. The effects of the drug on the cells of these children is so striking, and the condition so devastating, that doctors and scientists are wondering whether to proceed immediately to a clinical trial.
Hutchinson-Gilford progeria syndrome (HGPS), commonly known as Progeria is an extremely rare genetic disease, fewer than 100 children are currently diagnosed with it worldwide. He gained notoriety because children, despite health research for the first year or life, develop apparent features associated with age such as stiff skin, hair loss, brittle bones and cardiovascular disease. The condition has remained almost a complete mystery until 03 when two groups, one including geneticist Francis Collins, now director of the National Institutes of Health, and physician-scientist Leslie Gordon, a parent of a boy with HGPS, identified a progeria mutation in children.
The genetic defect disrupts the treatment of a protein called lamin A, which helps shape the nucleus of a cell. Accordingly, cells produce large amounts of an abnormal form of lamin A Progerin dubbed, and the blister pack and generally oval loop core. Somehow Progerin accumulation disrupts the development of most of children's tissues. Three drugs that hinder the creation of progerin are already tested on 50 children with progeria.
search for a drug that works through a different mechanism that could complement other experimental drugs, several groups studying progeria have recently turned rapamycin, a compound having various actions, including the suppression of the immune system . In 09, a research team has shown that administration of rapamycin may extend the life span of mice.
Could it therefore also help children with progeria? When children with the condition of cells exposed to the drug in lab dishes, they eliminate their abnormal accumulation of progerin and survive longer, Collins, Kan Cao of the National Research Institute on the Human Genome and colleagues today reported Science Translational Medicine . In addition, the nuclei in progeria cells go from "pretty darn abnormal" to "very beautiful, ovoid happy future," says Collins.
Normal cells are small amounts of progerin, convince many researchers that it contributes to natural aging, and the team found that rapamycin also promoted clearance of the protein in them. rapamycin, Collins says, inhibits the activity of a protein called mTOR and thereby promoting a process called autophagy that removes abnormal proteins, including progerin. This apparently enough for the kernel to return to its normal shape.
"This is a new approach worth pursuing" for the treatment of progeria, said Collins. "We now have another way to attack progerin," agreed Gordon, who was not affiliated with the study, but is the medical Director of the Progeria Research Foundation, of which she and her husband started and partially funded the work of rapamycin. "This is fantastic news."
The difficult question now is the speed to move, given the short life of children with progeria. Some scientists call for further study. "What is lacking is evidence that rapamycin is beneficial in a mouse model of the disease, which is an essential step before considering clinical trials," says molecular biologist Brian Kennedy, president of the Buck Institute research on aging in Novato, California. He noted that purely cellular studies in the new paper are difficult to reconcile with the results of a strain of mice engineered to have progeria. In these rodents, autophagy is already in overdrive, so Kennedy is skeptical that rapamycin could help these animals-and therefore children with progeria.
Everyone does not share the reluctance of Kennedy. Gordon, for example, noted that rapamycin has well known effects and relatively small side and has been tested in many children already, she and the other running from progeria current clinical trial are "seriously considering "the opportunity to begin to give an oral derivative of rapamycin children. Gordon said that progeria mouse model that worries Kennedy may not be the most accurate overview of the human condition. And although some rapid tests for the toxicity of rapamycin in mice with a form of progeria is justified, "I'm not sure we would have to wait 2-3 years for an efficiency study in mice, " she says.
Kennedy admits he would understand if Gordon, whose son progeria is now 14 years old, and other physicians pushed forward with a clinical trial. "The disease is so severe that it is an opening to try a drug in children," he said.
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