In children with progeria, a mutant protein accumulates in blood vessel cells, hampering their ability to grow and multiply or killing them outright.
In mice that produce this same toxic protein, the effect is similar: these vascular cells become damaged or die.

The findings of two research reports are published in the Proceedings of the National Academy of Sciences ( PNAS ).

Progeria is a rare and fatal genetic condition that causes accelerated aging in children.

A Brown Medical School graduate, Gordon created the Progeria Research Foundation in 1999, one year after her son, Sam, was diagnosed with the condition. The foundation raises public awareness and bankrolls research about the rare disorder, which causes hair loss, osteoporosis, and other signs of premature aging in children. Children with the disorder die almost exclusively of atherosclerosis at an average age of 13. This form of heart disease is typically seen in people over 60.

Progeria is extremely rare. The foundation reports that there are 42 known cases worldwide. Atherosclerosis, however, is quite common, affecting millions of adults. It prompts the build-up of fats, cholesterol, calcium and other substances in arteries. These plaques reduce blood flow and can cause clots that block blood vessels to the heart or brain, triggering a heart attack or stroke.

To better understand progeria, and find a cure, the foundation runs a medical and research database through Brown's Center for Gerontology and Health Care Research and operates a cell and tissue bank at Rhode Island Hospital. It also funds research, providing partial funding for one of the new research studies.

Using human skin tissue from the Rhode Island Hospital bank, researchers at Columbia University found that progerin, a mutant form of the protein lamin A, builds up in the nucleus of cells, particularly those of blood vessels. As a result of this build-up, the nucleus becomes deformed and these cells stop growing, moving and multiplying. Some cells die. Blood vessel cells most affected were those in smooth muscle. The result is support for a direct relationship between progerin and atherosclerosis.
The results of this study replicate findings included in previous research on the use of FTIs in progeria research.

A research team, led by scientists at the National Human Genome Research Institute at the National Institutes of Health ( NIH ), created and studied mice that carried the human form of the mutant lamin A gene.
The gene, harbored in an artificial chromosome, produced the same toxic protein that harms or kills cells in children with progeria. In parallel with the Columbia and Brown team, scientists found that these mice lost blood vessel cells in smooth muscle.

" This mouse model should prove valuable for testing experimental therapies for progeria, such as anti-cancer drugs and bone marrow transplants," said Francis S. Collins, director of the National Human Genome Research Institute and senior scientist on the NIH paper. " Now that we're armed with a better understanding of the underlying causes of atherosclerosis, we can also use this model to explore cardiovascular disease in general."

Source: Brown University, 2006


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