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I heard about this on Air America today.  Good news for someone, but I think
I'm too old, Ray
----- Original Message -----
From: "Peggy Willocks" <[log in to unmask]>
To: <[log in to unmask]>
Sent: Tuesday, June 20, 2006 10:36 PM
Subject: New hope with stem cells/GDNF


>A must-read!
>
> Peggy
>
> http://www.forbes.com/forbeslife/health/feeds/hscout/2006/06/20/hscout533366
> .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.
>
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