October 30, 2009

Discovery Lecturer outlines rare premature aging disorder

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Discovery Lecturer Elizabeth Nabel, M.D., left, with Gordon Bernard, M.D., and Jeff Balser, M.D., Ph.D. (photo by Anne Rayner)

Discovery Lecturer outlines rare premature aging disorder

Elizabeth Nabel, M.D., opened her Discovery Lecture by introducing the audience to a young boy, Sam Burns, who was diagnosed with a premature aging syndrome — Hutchinson-Gilford Progeria Syndrome (HGPS), or “progeria” — at 1 year of age.

Sam's diagnosis prompted the formation of a national effort to study this rare disease — an effort that is also revealing insights into cardiovascular disease more broadly.

“When Sam was born, Leslie Gordon, his mom (who is a pediatrician), did everything she could — as you can imagine a parent would — to try to discover the cause of progeria and do something about it,” said Nabel, director of the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health.

The first thing Gordon did was to form the Progeria Research Foundation, which began interesting investigators, including Nabel, in studying the disease.

“And probably the smartest thing she did was interest the current NIH director, Francis Collins, to work on it.”

Only 50 to 60 children in the world have this disorder, and these children uniformly die of heart attack or stroke in their early teens.

But the reasons behind the cardiovascular problems that lead to their deaths have long been a mystery.

In 2003, Collins' lab identified the genetic basis of progeria: mutations in the lamin A gene which result in a defective protein dubbed “progerin.”

That knowledge led Nabel and colleagues to create a mouse model to study the disease and its cardiovascular consequences.

Nabel recounted the research — from bedside to bench, and back to bedside — that has resulted in a possible new treatment for the disease; clinical trials of drugs called farnesyltransferase inhibitors are currently under way.

And the findings about the molecular basis of the disease may also reveal insight into the “normal” aging process, she said.

“We don't know what's the cart and what's the horse, but there are some really fascinating changes that occur as we age. And, progerin, perhaps, is a mirror on the aging progress.”

To view Nabel's lecture — and for a complete schedule of the Discovery Lecture series and archived video of previous lectures — go to www.mc.vanderbilt.edu/discoveryseries.