Embryonic stem cell breakthrough? Paralyzed rats walk.

[movielib]

http://www.forbes.com/forbeslife/hea...out533366.html

Stem-Cell Therapy Restores Movement in Paralyzed Mice
06.20.06, 12:00 AM ET

TUESDAY, June 20 (HealthDay News) -- In what experts are describing as a major advance, scientists have used embryonic stem cells to form new, functional nerve cell connections in formerly paralyzed mice that effectively restored the animals' limb movement.

While success in humans remains a distant goal, the achievement is "proof of principle" that stem-cell grafts such as these might someday be used to treat spinal cord injury, ALS (Lou Gehrig's disease), Parkinson's disease and other crippling neurological conditions, one expert said.

"This is something that we've been looking for for 30 years," said Naomi Kleitman, program director of the Extramural Research Program at the U.S. National Institute of Neurological Disorders and Stroke.

Kleitman was not involved in the study, but her office helped fund the research. She called the finding "exciting, because it proves the principle that with the right combination, we can coax [nerve] cells out, and now we know what to build on."

The findings will be published Monday in the journal Annals of Neurology.

Numerous studies have come out over the past few years showing that embryonic stem cells can form nerve cells in areas of the spinal cord damaged by injury or disease. But getting these motor neurons to make functional connections to muscle has been a frustrating roadblock.

"In the simplest [neuronal] relay, a brain cell talks to the motor neuron in the spinal cord and says, 'Move that muscle,' " Kleitman explained. "Then, the motor neuron reaches out of the spinal cord to the muscle using these long fibers called axons. They communicate with the muscle, send an impulse, and the muscle contracts."

But this seemingly simple network relies on a complex partnership of growth factors and signaling chemicals -- each vital to the process. So, research aimed at deciphering these players and their connections has continued.

"It's like a detective story where if you don't put all the clues in order, you wind up going off in the wrong direction," Kleitman said.

The new study was conducted by a team at Johns Hopkins University School of Medicine, led by Dr. Douglas Kerr. His group concocted a kind of neural "recipe" that satisfied all of the conditions needed for the successful growth and networking of new motor neurons.

Starting in the laboratory, they first used specific growth factors to spur mouse embryonic stem cells to differentiate into motor neurons. Then they added two chemicals -- retinoic acid and sonic hedgehog protein -- to help these new cells feel more at home in the spinal-cord environment.

The next step was to deliver these primed cells into the spinal cords of mice previously paralyzed by a viral infection.

But another roadblock loomed.

"We know that there are proteins in this area that inhibit axons from growing in adult animals," Kleitman explained. The proteins are linked to the protective myelin sheath that coats nerve fibers. "They're part of how we keep our nervous system from going haywire during normal function," she said.

To overcome this resistance, the Hopkins team added two agents -- cyclic AMP (cAMP) and the drug rolipram -- to the mix. According to Kleitman, these molecules "block the 'stop sign,' so that now the axons can grow."

But there was one more hurdle -- it's one thing to allow axons the freedom to grow, but to grow where? "You've got pretty long distances to cover, so one of the things you need is a 'target' that's screaming out like a neon sign, 'Come here!' " Kleitman said.

The Hopkins group created just such a target by applying a powerful neural growth factor, called GDNF, to the remains of nearby, deadened sciatic nerve cells. The GDNF -- derived from fetal mouse neural stem cells -- essentially "called out" to the growing axons, urging them to make the connection.

In the end, this complex biochemical "recipe" worked, the Hopkins team reported.

Of the more than 4,100 new motor neurons created in one mouse's spinal cord, about 200 exited the cord and 120 found their way to skeletal muscle. These new connections looked identical under the microscope to those seen in healthy mice, the researchers said.

What's more, 11 of the 15 treated, previously paralyzed mice began to regain muscle strength and function and were more mobile in their cages.

However, this restoration of function did not occur when the researchers left out even one of the ingredients from the mix.

According to Kerr, his team has simply tried to recreate the environment that directs neural formation early in fetal development.

"As adults, our cells no longer respond to early developmental cues because those cues are usually gone," he explained in a statement. "That's what we believe we have changed [here]. We asked what was there when motor neurons were born, and specifically what let motor neurons extend outward. Then we tried to bring that environment back, in the presence of adaptable, receptive stem cells."

Kleitman called the work "elegant," but stressed that much more research needs to be done before this strategy could be applied to human patients. "To take this to a person you need to work with something larger than a rat leg -- that's only about an inch of [neuronal] growth," she said. Scientists also need to make sure that certain risks associated with stem-cell therapy -- most notably, increased tumor formation -- can be minimized.

However, Kerr said his group is already engaged in a federally funded study, set to start this summer, that will try and replicate the mouse findings in a larger model -- a pig -- using human embryonic stem cells. If that effort proves successful, FDA-approved human clinical trials might be a few years away, the researcher said.

Kleitman said the new advance has everyone in her field optimistic.

"We get really excited when good science leads to more good science, that then leads in a direction that can really help people," she said.

[muggins]

Starting in the laboratory, they first used specific growth factors to spur mouse embryonic stem cells to differentiate into motor neurons. Then they added two chemicals -- retinoic acid and sonic hedgehog protein -- to help these new cells feel more at home in the spinal-cord environment.

Eh?

[crazyronin]

Sonic hedgehog protein explained

[kvrdave]

I thought this type of thing has been done with adult stem cells already. Might be mistaken, though.

[Breakfast with Girls]

The lead researcher on this project:

[Giantrobo]

Promising news.

[Lord Rick]

misleading thread title?

Title says "walk" but article says increased movement.

Still good news, though.

[movielib]

Originally Posted by Lord Rick

misleading thread title?

Title says "walk" but article says increased movement.

Still good news, though.

I read several different stories on this before choosing the one and posting it. Some of those stories said walk (e.g. http://www.cbsnews.com/stories/2006/...n1734662.shtml ) so I guess I picked that up.

[kvrdave]

Well, while in the shower this morning, Paul Harvey talked about this study. Then he said, "Imagine how many Christopher Reeves would be walking if this type of research were legal."



It is legal you old goat. In fact, if I wanted to be an embryo farmer and just knocked up women to take embryos rather than waiting around for abortions, I could. That is how legal it is. It couldn't be any more legal.

[raven56706]

my fiance's dog was paralyzed from the waste down and after surgery, he is slowly walking again....

[heavy liquid]

Originally Posted by movielib

I read several different stories on this before choosing the one and posting it. Some of those stories said walk (e.g. http://www.cbsnews.com/stories/2006/...n1734662.shtml ) so I guess I picked that up.

I read another very in-depth article on this yesterday, but can't seem to find it now. I did find this which was also in the article I read yesterday:

http://ca.news.yahoo.com/s/21062006/...paralysis.html

The paralysis wasn't completely gone, but six months after treatment, 11 of the 15 animals could bear weight, take steps and push away with the affected leg.

Sounds like they could almost walk. Still, this is amazing news either way! Hopefully it's just a matter of refining the procedure. I hope everything goes smoothly and they're actually able to help people soon.

[movielib]

Originally Posted by kvrdave

Well, while in the shower this morning, Paul Harvey talked about this study. Then he said, "Imagine how many Christopher Reeves would be walking if this type of research were legal."



It is legal you old goat. In fact, if I wanted to be an embryo farmer and just knocked up women to take embryos rather than waiting around for abortions, I could. That is how legal it is. It couldn't be any more legal.

Paul Harvey was already going senile when I listened to him in the '60s.

[dave-o]

Originally Posted by kvrdave

Well, while in the shower this morning with Paul Harvey...

[kvrdave]

I don't judge you.

[dave-o]

Originally Posted by kvrdave

I don't judge you.

Fair enough, as long as we don't have to hear....(wait for it).......



the rest of the story.

[kvrdave]

[whaaat]