Paralyzed Mice Walk Again

Samuel Stupp has a bunch of mice that used to drag their hind legs behind them when they crawled around his Illinois lab, but they have miraculously regained at least partial use of their rear legs.

Astonishingly, their severed spinal cords have been repaired, at least partly, without surgery or drugs.

All it took was a simple injection of a liquid containing tiny molecular structures developed by Stupp and his colleagues at Northwestern University. Six weeks later, the mice were able to walk again. They don't have their former agility, but their injuries should have left them paralyzed for life.

Stupp is on the cutting edge of one of the most exciting fields in medical research: regenerative medicine. If he and others in the field are on the right track, one of these days tragic diseases like Parkinson's and Alzheimer's will be a thing of the past. And the crippled will walk again as the human body repairs itself in ways that it cannot do today.

Preliminary results with lab animals have been encouraging, but what works for mice and rats frequently does not work for humans. But if it does, medicine will enter a new era.

Solution: Think Small

Stupp's team concentrates on combining the incredibly small world of nanotechnology with biology, creating molecules that self-assemble into large molecular structures that can literally "hug" around cells in the human body. That allows them to take charge of key cells present in the body and dictate how they will perform, or, in the case of stem cells, what they will become.

That's a slightly different approach than others in the field are following. Researchers at the University of Michigan, for example, are making "nano particles" that are thousands of times smaller than a single cell. They are small enough to slip through tiny openings in a cell, potentially delivering cancer-killing drugs directly to a damaged cell.

James R. Baker, who runs the university's nanotechnology institute, calls it the "nanotechnology equivalent of a Trojan horse."

Compared to Baker's horse, Stupp's molecular structures are huge, although still too small to be seen with the unaided eye.

'Glial' Cells Key to the Nervous System

The mice in Stupp's lab can move about better these days because the designer molecules attacked the precise reason why a spinal cord is unable to heal itself. When the cord is severed, glial cells in the body create a scar called a "glial scar."

"The scar appears within weeks after the injury and this basically paralyzes the patient forever," Stupp said. "The scar is like a physical blockade that prevents axons from regenerating and growing."

Axons are fibers that extend out from nerve cells and attach to other cells, thus allowing the brain to command the body to carry out its functions, like moving its legs. Stem cells present in the body that have not yet developed into a specialized cell should be able to differentiate into new neurons, thus making regeneration possible, but often the stem cells become glial cells instead, making recovery that much more difficult by reinforcing the "blockade."

A couple of years ago, Stupp said, his team discovered that it could pack its nanostructure with a biological signal that commands the stem cells to turn into neurons, not glial cells. The same signal, he said, orders the axons to grow.

And that's just what Stupp and his colleagues found when they dissected the damaged spinal column in some of the mice.

"We see regenerated axons across the lesion," he said. "That's the exciting part. Regeneration of axons across the lesion is very significant."

No Drugs, No Surgery

What it means is that the spinal column is, indeed, healing itself, and without the aid of drugs.

But what happens to those nanostructures after they've done their work? One of the concerns in the field of nanotechnology is that scientists might create tiny machines that could be used for great mischief. They might make manufacturing so cheap, for example, that any country could afford to become a military superpower. There is no chance of anything evil coming out of this, Stupp said.

"These nanostructures are completely biodegradable," Stupp said. "They disappear within weeks."

So they do their work and go away.

Stupp is now expanding his research into Parkinson's disease.

"It's just the very beginning, so this is extremely early," he said. "We are introducing these nanostructures in the brain of mice that have Parkinson's disease. We have seen very interesting functional recovery."

In the end, it might turn out that Stupp's work is only part of the solution. Like his associates at the University of Michigan, he might find that his nanostructures make great drug delivery systems. Certain solutions may require the introduction of stem cells, he said, so that controversy isn't likely to go away. But maybe a marriage between nanotechnology and traditional medical procedures might be just the ticket.

"What might really work is the integration of the two," he said.

Stupp's results are encouraging, although very preliminary. But he is so convinced that he's on the right track that he recently unveiled his mice, and their partial recovery, during a meeting in Washington of the Project on Emerging Nanotechnologies. The project is a public interest program sponsored by the Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts.

The mice are not pretty to watch. They still struggle to walk, sometimes dragging one foot. So it's a partial victory at this point. But it's a significant milestone in a field that is in its infancy.

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