Research groups at UCLA and the National Institutes of Health have discovered a potential treatment for a rare genetic disease in which children age prematurely and usually die by the time they reach their teens.
The finding, reported online today in the Proceedings of the National Academy of Sciences, showed that a class of cancer-fighting drugs corrected abnormalities in cells taken from patients with Hutchinson-Gilford progeria syndrome, which affects one in 4 million children.
The drugs might help prolong the children’s lives or block a host of problems, such as poor growth, loss of hair and body fat, and atherosclerosis, scientists said.
The finding also opens a potential avenue of research into the causes of normal aging, they said.
Children who have the progeria syndrome, which was identified more than a century ago, appear normal when born but, within the first year, their growth slows dramatically. By about age 2, they have lost their hair. They generally never reach 4 feet in height nor surpass a weight of 35 pounds.
In 2003, a team of scientists led by Dr. Francis S. Collins, director of the NIH’s National Human Genome Research Institute, reported that they had found the gene causing the defect. Known as LMNA, it directs creation of a protein called lamin A.
Under normal circumstances, lamin A proteins accumulate in a layer just inside the cell nucleus.
But in Hutchinson-Gilford progeria patients, lamin A never gets to its correct destination. Instead, it builds up on the membrane of the nucleus. The nucleus becomes misshapen, with bulging projections pushing into the cell’s cytoplasm.
In the two separate papers, Collins’ team and that of Drs. Stephen Young and Loren Fong at UCLA reported that they had eradicated the projections in human cells by using a class of drugs known as farnesyltransferase inhibitors.
Young and Fong had earlier shown the same effect using the drugs on mouse cells containing the defective human LMNA gene.
The drugs prevent lamin A from reaching the nuclear membrane so it cannot build up there.
The scientists are uncertain if the drug treatment will translate into a useful therapy.
The next step, both teams said, would be to treat mice genetically engineered with the human gene for Hutchinson-Gilford progeria. Collins said a human clinical trial could begin as early as spring if the results were promising.
Some farnesyltransferase inhibitors have been extensively tested for safety, including in children, because of their promise in fighting certain cancers. Several are in advanced clinical trials.
“We just really are phenomenally fortunate,” said Dr. Leslie B. Gordon, medical director of the nonprofit Progeria Research Foundation, assistant professor of pediatrics at Brown University in Rhode Island and a co-author on Collins’ team.
Gordon, who has a child with progeria, said it is unlikely that the drugs would have undergone such costly and extensive testing for progeria itself because the disease is so rare.