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Stem cell technique could help those with fast-aging disease

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Science and Technology,Health
A recently developed stem cell technique could help researchers find a cure for the rare, fatal fast-aging disease known as Hutchinson-Gilford progeria syndrome, as well as help scientists better understand the normal aging process.

Progeria is caused by a single mutation to the LMNA gene, which results in the defective production of a protein named lamin A. This protein is needed to build the membranous shell around a cell's genetic material.

Children with the disease undergo rapid aging and most don't live to become teenagers. More than 90 percent of them die from complications related to hardening of the arteries and blood vessels. There's no known treatment and because the disease is incredibly rare -- only 64 children are known to have it worldwide -- scientists don't have much opportunity to study it.

Over the past five years, scientists have learned how to use targeted retroviruses that selectively alter DNA to roll back specific cell types such as skin cells and muscular cells into what are called induced pluripotent stem (iPS) cells. These stem cells, like embryonic stem cells, can go on to form other types of cells depending on the kind of tissue into which they're transplanted.

Several researchers, including those who published their findings this week in the journal Nature, are exploring this technique's usefulness in understanding exactly how progeria does its damage.

The researchers, led by geneticists Juan Carlos Izpisua Belmonte and Guanghui Liu at the Salk Institute in La Jolla, Calif., used the technique on skin cells obtained from people with progeria. After reprogramming these damaged cells to become iPS cells, the scientists found that the cells no longer showed the disease's telltale defects to the nucleus.

"In other words, these progeria iPS cells looked like normal young, healthy iPS cells," Liu said.

When the scientists transplanted those cells back into muscular tissue in a petri dish, though, the progeria cells resumed their old tricks. That's not surprising, Liu said, as simply resetting these cells to a stem cell state won't cure them of their underlying genetic defects.

But the technique will allow scientists to more easily study the onset of progeria and its progression, which will hopefully allow researchers to one day develop therapies that stop or reverse damage caused by progeria's rapid aging. In fact, Liu said, his lab is currently working on an important step of this process by developing a technique that can fix the genetic mutation responsible for progeria while it's in a stem cell state.

"Hopefully our efforts will be useful to generate ... [non-symptomatic] progeria cells and help those progeria patients in the near future," he said.

In addition to helping those with progeria, such techniques could also help scientists better understand the process of normal aging by being able to see cells age the equivalent of a normal lifetime over the course of a few weeks.

Tom Misteli, a gene biology researcher at the National Cancer Institute in Bethesda, said that while the research isn't particularly novel, as it essentially uses the same techniques previously developed to create regular iPS cells, it further confirms the technique's usefulness in better understanding progeria.

"It's a first very small step, but it won't lead to any immediate therapeutic application," he said.

Geneticist Brian Kennedy, president and chief executive officer of the Buck Institute for Research on Aging in Novato, Calif., agreed that the therapeutic potential remains some way off, but added that it's impressive nonetheless.

"From an understanding point of view, it's a great tool," he said.

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