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Allen Institute will give preview of spinal-cord atlas

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When Jane Roskams started studying spinal-cord injuries, she kept coming across cells she couldn’t identify. Other experts were often stumped, too.

“I quickly found out what a black box the spinal cord is,” said the University of British Columbia (UBC) scientist. “People don’t even know what half the cells are, let alone what they do.”

So when a Seattle neuroscience lab created by Microsoft billionaire Paul Allen was casting around for its next project, Roskams offered a suggestion: Create a detailed map of the spinal cord.

Today, the Allen Institute for Brain Science is releasing the first data from that project, which is expected to be finished by early next year.

The spinal-cord atlas will provide a boost to research on Lou Gehrig’s disease (ALS), Multiple Sclerosis and other disorders that attack the nervous system, Roskams said. It also will help efforts to treat, and perhaps repair, spinal-cord injuries.

“It will enable us to look inside each group of cells in the spinal cord and know what it is that makes them special and different from the cells around them,” said Roskams, of UBC’s Brain Research Centre. “I don’t think there will be a lab in the world working on spinal-cord injuries that does not access this as soon as it goes online.”

Allen is picking up most of the tab for the $2.3 million project. But the institute also raised about $600,000 from private donors and diverse groups, including Paralyzed Veterans of America (PVA), The ALS Association, Pemco Insurance and the pharmaceutical company Wyeth.

About 250,000 Americans are living with spinal-cord injuries, and about 10 percent are veterans, said Thomas Stripling, PVA’s director of research and education.

The severity of spinal-cord injuries from combat has been increasing, partly because medical care allows soldiers to survive wounds that previously would have been fatal. Also, while the body armor worn by soldiers in Iraq and Afghanistan protects much of the spine, it exposes the neck, where injuries lead to more extensive paralysis, Stripling said.

Advances in treatment have made it possible for victims to live longer and more comfortable lives, and Stripling said he hopes the spinal-cord atlas will lead to even more improvements.

Robotic analysis

Founded in 2003 with $100 million in seed money from Allen, the Seattle institute’s first project was a detailed atlas of the mouse brain. Though mice and men differ in many ways, they share more than 90 percent of their genes.

The spinal-cord project also will use mice.

As with the brain, the new project will rely on robotic systems to analyze paper-thin slices of spinal cord.

The analysis will reveal which genes are switched on in each region of the cord, down to individual cells.

Every cell in the mouse spinal cord contains a full set of about 20,000 genes, but not all of those genes are active in every cell. The pattern of activation determines how a cell works and gives each cell type its special properties.

“Every cell has a story to tell,” said Allan Jones, the institute’s chief scientific officer.

Knowing which genes are switched on will provide researchers with clues about what goes wrong in disease, Roskams said. For example, Lou Gehrig’s disease, or amyotrophic lateral sclerosis, attacks only the nerves in the spinal cord that relay orders from the brain to move the muscles and limbs. Generally, the disease moves upward from the lower part of the spinal cord. The result is progressive paralysis.

Once researchers know more about what makes the affected nerves unique, the closer they will come to designing drugs or otherwise tweaking cells to make them resistant to attack.

“The cells that lie in the spinal cord hold the clues to our understanding of how these diseases develop and what we can do to try to repair the spinal cord and brain when those particular diseases set in,” Roskams said.

The institute also will analyze both brains and spinal cords of mice at various stages of development, including before birth and during old age. That’s particularly exciting for spinal-cord research, because young animals — including humans — recover more quickly and completely from spinal-cord injuries than adults.

Some of the genes and materials involved in the initial growth and wiring of the nervous system are still active in young animals, but disappear later in life. If scientists can identify key genes, it may be possible to switch them back on, or develop drugs that would lead to nerve Regeneration.

Growing evidence also suggests that many brain and nerve diseases, including schizophrenia and autism, may be rooted in early development of the nervous system, Jones said.

“Something is setting the stage very early on in life,” he said. “Maybe something is not getting wired up properly … but we’re not sure.”

Next: the human brain

As Allen’s initial seed money is used up, the institute hopes to find other sources of funding for future projects, including its ambitious plans for an atlas of the human brain.

That project, which is still in the planning stages, will cost about $55 million and take four years, said chief operating officer Elaine Jones. She’s looking for donors and may request money directly from Congress.

All of the institute’s data are available free online. The mouse-brain atlas gets about 14,000 visitors a month and has been cited in nearly 160 scientific studies since it was unveiled less than two years ago.

The site is so popular that a satellite server was set up at a research center in Sweden to improve access for European scientists. Another will open soon in Japan.

By Sandi Doughton
Seattle Times science reporter
Copyright © 2008 The Seattle Times Company

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