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January 29, 2004
CENTER GRANTEE UNCOVERS NEW PROTECTIVE PROCESS
IN SPINAL MOTOR NERVE CELLS
Sometimes, in the midst of turmoil, having one small thing
made right can make a world of difference. That's the philosophy underlying
a body of research at the Packard Center -- the idea that even a small
improvement or a small salvaging of what's normal in motor neurons can
keep things going until a cure arrives. Or, perhaps, several small "salvages,"
taken together, might keep cell death at bay and turn ALS into a manageable
chronic disease.
In that vein, research by the latest Center grantee, neuro-researcher
Katrin Andreasson, takes on added importance. Andreasson, a scientist
with Johns Hopkins School of Medicine, has focused on a well-known chemical
pathway that goes awry in a host of neurological diseases, including ALS.
And recently, she and her co-researchers have found a potential bright
spot on that route, a built-in molecular "button" that, when
"pushed" unleashes a natural protective cascade, a set of reactions
in nerve cells that damp down damage.
The larger pathway centers on molecules called COX1 and COX2, now famous
in medical circles because inhibiting them forms the basis for aspirin's
good effects, as well as for those of pain-relievers and anti-inflammatories
like Advil or Celebrex.
Andreasson and others have found a number of nerve diseases, from stroke
to ALS, accompanied by an undeniable rise in COX 2. "COX2, we know,
isn't harmful at low levels. In fact, it's necessary within individual
nerve cells for learning and memory. It has a role in natural immune function
and perhaps even sleep," says Andreasson. "But higher levels
are linked to toxicity. And it was after we tried to map this out that
we saw an unexpected--and potentially useful--effect."
COX1 and COX2 are key enzymes in producing agents called prostaglandins
that, in many ways, act like hormones. "Some prostaglandins are notorious,"
says Andreasson. Certain ones help bring about symptoms in asthma, for
example. So when she and colleagues applied one suspect prostaglandin
to a rat spinal cord culture that models ALS, they expected damage to
be intensified. But the opposite was the case. "The spinal neurons
were dramatically protected," Andreasson says.
Trying to see what might account for the good effect, the team focused
on different tissue sites targeted by the prostaglandin -- there are four
of these docking sites or, as they're more appropriately termed, receptors.
When the team stimulated one particular receptor, called EP2, in the spinal
cord model, the effect was again dramatic. Remaining nerves were protected
and the diminished areas in the spinal cord were again rich in motor nerves.
"We were totally surprised that such a protective process exists
naturally," Andreasson remarks. With her Packard Center grant, Andreasson
will test other prostaglandin receptors for positive effects. She also
plans to try stimulating EP2 receptors in living SOD1 mouse models of
ALS. "We're excited by the possibility that this may lead to a therapy."
>>more Recent News
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| Recent news from the Robert Packard Center
for ALS Research: |
| In ALS, It’s Not the Number of Ailing Astrocytes That Counts - June 12, 2008 |
| Leaky Blood Vessels Add To ALS Damage, Could Offer New Repair Site - June 10, 2008 |
| William H. Adams Foundation Pumps New Energy, Funds into Search for ALS Cure - May 6, 2008 |
| Tell-Tale Protein Clumping in ALS is Less Complex Than Expected - April 10, 2008 |
ALS Mouse Study Highlights Astrocytes' Strong Potential as Therapy Target - February 7, 2008 |
| Exciting New Human ALS Trial: Lithium and Riluzole - February 7, 2008 |
| ALS Treatment: A Matter of Cleaning House? - December 19, 2007 |
New Study Brings What Goes Wrong in Inherited ALS into Focus - September 18, 2007 |
| New ALS Protein Could Be a Keystone - August 9, 2007 |
| Muscles More Than Passive Victims in ALS, Study Suggests - June 29, 2007 |
| Saer and O’Neill Named Packard Center Board Co-Chairs - June 28, 2007 |
Self-Attack? Self-Repair? First Real Look at Gene Activity in ALS Models Sparks Thirst for Answers - May 3, 2007 |
| Model of Accelerated Familial ALS Sheds Light on Disease Process - April 6, 2007 |
| Early News From First Large Search for Sporadic ALS Genes - February 20, 2007 |
| Human Stem Cell Transplants Mature Into Neurons and Make Contacts in Rat Spinal Cord - February 14, 2007 |
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