Miércoles 29 de Noviembre de 2006, Ip nº 181

UR seeks stem cell breakthrough
Por Lauren Stanforth

Quietly but steadily, under the watchful eye of some of the nation's top scientists, hundreds of technicians and researchers isolate cells and scrutinize data in 18 immense laboratories at the University of Rochester Medical Center. They're teasing out the secrets of stem cells, the building blocks of the body, in the hope of finding cures for diseases such as Parkinson's, diabetes and multiple sclerosis.

Some of the work has sparked controversy because it uses days-old human embryos, which some researchers believe can develop into many tissues of the body and in larger quantities than possible with stem cells taken from adult tissue. In turn, discoveries using those cells may lead to many more treatments, for conditions as wide-ranging as spinal cord injuries and blood cancers.

But the issue is not as simple as many political pundits, and some scientists, have led the public to believe. Using stem-cell science to treat people may be close to realization for some conditions but many years away for others. Federal funding for new embryonic work is banned, but private funding is flowing. Using embryos could be vital for some discoveries but completely unnecessary for others.

One UR scientist, neurologist Dr. Steven A. Goldman, recently had a breakthrough, then a setback, in Parkinson's treatment. Yet he might be close to finding a treatment for some neurodegenerative diseases.

Details of the daily work of researchers such as Goldman are largely unknown to the public, if only because the science is so complex and arcane. But shining a spotlight on his lab may improve understanding of the research that could one day change medicine.

"To think, you can actually start to do the things you dream about," Goldman said.

UR expands reach

Directly across from Goldman's desk in the Arthur Kornberg research building next to Strong Memorial Hospital is a dry eraser board filled with scribbling. The notations would probably mean nothing to 99 percent of the population. But for Goldman, it's like reading the back of a cereal box. "It's pretty easy actually," he said.

Goldman is sketching out what is called a progenitor cell, a cell that leads to the formation of the brain's structures. But one has to determine how and why the cell changes to learn how to manipulate it for other purposes. That's where the mapping of the cell comes in, finding the different genes present in each cell that, with the help of molecular signals, cause the cell to turn into its final form.

The cell sketched in black marker on Goldman's board is an astrocyte progenitor, a cell that eventually turns into the star-shaped network of branches and fibers that make up the physical structure of the brain.

This explanation is as simple as can be derived from Goldman's intensely complex work. But in the corner of the board, there is a sign of something more people could relate to — drawings done by three of Goldman's children, who entertained themselves during a visit to his office.

Goldman, 49, a native of Philadelphia, calls himself a "Manhattan expatriate," one of the many who flock north to get away from the crushingly long commutes and insane real estate prices of the New York City area. Goldman and his wife, Maiken Nedergaard,a professor of neurosurgery, worked there as scientists for about 20 years at Weill Medical College of Cornell University, one of the best medical research institutions in the country.
The couple likely could have gone to their pick of elite institutions when they decided to leave Cornell. They chose Rochester in 2003, in part because, as Nedergaard said, "it was a good place to raise the kids." That the University of Rochester Medical Center was attempting to bolster its research division also was an important factor. Goldman and Nedergaard now live in Webster with their five children, ages 7 to 16.

UR built the $36 million Arthur Kornberg Medical Research wing in 2001 and invested millions more to attract the country's top scientific minds. Goldman and Nedergaard were among them, said Dr. Bradford C. Berk, CEO of the medical center.

Berk's goals for stem cell research at the UR are lofty. He believes UR can be one of the top programs in the world for cancer and neurological stem cell research, and the recruitment of two or three more researchers should help UR reach that goal, said Berk, himself a cardiovascular researcher who became the medical center's CEO this year.

"When we can recruit an internationally recognized guy like Steve Goldman, he significantly improves the total research environment," Berk said.

The creation of Goldman and Nedergaard's labs brought in about 50 staff positions and millions more in federal and private research dollars.

Nedergaard investigates how particular conditions affect tissue, and Goldman looks at how to change those reactions to eliminate disease. Their work sometimes overlaps. On a recent afternoon Nedergaard stuck her head into Goldman's office to ask who was using a piece of donated living brain tissue that was being removed during a neurosurgery at the hospital.

"It's 20 years later and she's still in the lab next door," he said.

Abdellatif Benraiss, an assistant professor in Goldman's lab, worked with Goldman at Cornell for about five years until he and his family decided to leave New York after the 9/11 terrorist attacks. Benraiss, a native of Morocco, worked at a university in Paris but didn't like living in another big city. Goldman recruited him to UR this year.

Benraiss is continuing the work that he started at Cornell on Huntington's disease, a degeneration of neurons in the brain that leads to uncontrolled movements and emotional disturbance.

"I have more responsibility here and much better space," Benraiss said.

From canaries to people

Although discussions of stem cell research didn't explode nationally until the federal ban on new research involving embryos in 2001, Goldman and scientists like him have been working on the concept for decades.

Goldman began looking for stem cells, the cells where all cells originate, in the brains of canaries at Rockefeller University in the early 1980s. Canaries are of particular interest to scientists because new neurons are created in the male brains of canaries every year so that they can learn new songs. To immortalize his start in this science, Goldman has a porcelain canary sitting on his desk.

In the 1990s, Goldman went on to search for brain stem cells in mice, rats and monkeys. A technique first had to be developed for isolating the cells before he and other researchers could work on manipulating them.

Goldman and his team of assistant professors, students and technicians are now attempting to ease disease symptoms in mice and rats with the cells they have identified. But a recent breakthrough in Goldman's lab is a perfect example of the promise of stem cells — and the problems they can create.

Goldman's team found cells that can turn into dopamine-producing neurons. Dopamine is the chemical messenger between nerve cells that is lacking in the brains of people with Parkinson's disease. Some rats were injected on one side of the brain with a chemical that simulates Parkinson's symptoms. But because rats do not have the same motor skills as people, the movements normally associated with Parkinson's aren't apparent. So the rats were given a stimulant so they would move around. Because only one side of the brain was affected by the chemical, the rats ran in circles.

But when the rats were injected with new cells on that same side of the brain, their circular movements disappeared. After the rats were euthanized, however, an examination of their brains under a microscope revealed something else — tiny, noncancerous tumors.

The new cells weren't just generating dopamine neurons, thereby eliminating Parkinson's symptoms, they were growing unnecessary tissue as well. The results were published in October in the journal Nature Medicine.

Goldman feels the starter cells perhaps weren't purified enough to ensure that other growth cells weren't sneaking in.

However, "for me it was a glass half-full because it was great to see neurological repair," Goldman said.

A cure in sight?

Other study findings for another disease so far show no such glitches, and Goldman's team presented that research early this month at a meeting of the National Multiple Sclerosis Society.

In this recent experiment, Goldman used mice he called "shiverer mice" that are bred to be born without brain myelin, the sheath that surrounds the nerves and aids in the rapid transmission of messages from neuron to neuron. Myelin degenerates in multiple sclerosis and leukodystrophies, rare genetic disorders such as Krabbe disease. The mice appear to shiver as a result, hence the name.

The details of the research cannot be released until Goldman's team publishes its data, something journals require for exclusivity. But after injecting a formulation of the starter cells that give rise to myelin, some of the mice have gained motor skills and have lived past eight months. Normally, these mice do not live longer than three or four months.

Goldman said the work likely will be used to start a clinical trial in people. But it could take up to two years to meet the Food and Drug Administration's requirements for mass-producing the purified cells.

Goldman was one of about 50 researchers who attended the MS society conference. The MS Society has split $3.8 million among researchers for work throughout the world, including Goldman's. "The data (Goldman) showed us was spectacular. We were blown away by it," said Timothy Coetzee, associate vice president of research initiatives and outreach for the MS Society.

Also of note in Goldman's myelin research is what the team used to produce the cells. Goldman's lab used cells derived from adult tissue, not the embryos that some scientists say the industry needs to best produce stem cells. Goldman said some stem cells can be found in adult tissue, thus eliminating the need to use embryos. But other stem cells, such as those needed for Parkinson's research, can only be found in the embryo.

Goldman used an embryonic line of stem cells for his Parkinson's work, but the cells were derived from a line that existed before the federal ban — so he receives federal funding for it.

The university is currently working on devising a new space inside Goldman's lab that will be separate from the rest of his National Institutes of Health funded-research so he can work with new embryonic lines. Currently, the NIH requires that no one receive funding for any projects if they're using the same space for unsanctioned embryonic work. Even though the NIH won't fund it, Goldman said some private organizations have pledged money to the UR to do the research — as has happened at other research institutions across the country.

Goldman said his work with myelin replacement could be used in people in one to two years, and his Parkinson's work in perhaps three to five years. But for other diseases that people have hitched to the stem-cell star, such as Alzheimer's disease, there is still much work to do, he said.

Goldman wrote an opinion piece last year in the journal Neurology in which he said many stem cell discoveries have a long way to go.

"As physicians, we need to clearly define for the broader public and for our patients where science ends and religion takes over," Goldman wrote.

"Yet to do so, we need to be clear where the science is at the moment, where it may lead, and what difficulties lie ahead."

  26/11/2006. The Rochester Democrat and Chronicle.


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