Feed: SPINAL CORD INJURY RESEARCH AND ADVOCACY
Posted on: Thursday, September 06, 2012 7:45 AM
Author: unite2fightparalysis
Subject: CNS Regeneration Project supported by Unite 2 Fight Paralysis

 


 
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 In 2010, Drs. Kai Liu (Hong Kong University), Zhigang He (Harvard University) 
and Oswald Steward (Reeve-Irvine Research Center) were part of a team of 
researchers who published a groundbreaking paper in Nature Neuroscience, 
showing massive regeneration of the corticospinal tract (CST) for the first 
time in history. This is very significant because the CST pathway controls 
locomotion, and is thought to be the most difficult to regenerate.

Regeneration was achieved by deleting an enzyme called PTEN (a phosphatase and 
tensin homolog), which controls a molecular pathway called mTOR that is a key 
regulator of cell growth. PTEN activity is low during early human development, 
allowing cell proliferation. PTEN then turns on when growth is completed, 
inhibiting mTOR and precluding any ability to regenerate.

In late 2011, Dr. He led a group who published a paper in Nature that showed 
combining PTEN with SOCS3 (suppressor of cytokine signaling 3) produced four 
times the number of axons to regenerate, and they grew 10 times the distance 
compared to using PTEN or SOCS3 inhibition alone. This suggests that PTEN and 
SOCS3 are suppressing growth factors and pathways that promote axon growth, and 
although each gene acts on different pathways, there is some synergy between 
them.

U2FP was interested in these discoveries and invited a group of researchers to 
meet with them to discuss their application in treating chronic spinal cord 
injuries. As a result of that meeting, a team that includes Drs. Steward, He, 
Liu and Jerry Silver (Case Western Reserve University) is now collaborating to 
translate this research to the clinic.

Dr. Silver is considered an expert in research related to the injury site and 
his recent peptide discovery will be added to this collaborative research 
project, allowing for even greater regeneration. His acute model peptide 
studies are now going forward to test in the chronic model. U2FP has 
established a Research Fund to support this collaboration in an effort to move 
it forward faster.

Moving forward to a preclinical phase is predicated on achieving three 
milestones:
1.Obtaining definitive evidence that regeneration can be safely achieved by 
deleting PTEN and SOCS3 to enhance recovery of function.
2.Obtaining definitive evidence that the combination therapy can be delivered 
in a therapeutically relevant time frame. Ideally experiments would be 
conducted on chronic injury models.
3.A therapeutic approach and delivery system must be identified that can be 
translated to a therapy. Considerable progress has already been made to achieve 
this milestone by Gail Lewandowski’s lab at the Reeve-Irvine Center.

It is important to note that since the initial discovery, the number of 
scientists doing PTEN research has greatly expanded. There are at least 20 
additional labs working in this area of research which will provide increased 
knowledge and accelerate the progress in moving this therapy forward. 

U2FP is comprised of individuals with a personal stake in advancing therapies 
to treat chronic SCIs and we would like for you to join our efforts and support 
this research. The results of this research will be reviewed by U2FP’s 
Scientific Advisory Board for recommendations. Meanwhile, you can support the 
work of this collaboration by donating to the U2FP Research Fund.  
<http://www.z2systems.com/np/clients/u2fp/donation.jsp?campaign=23> You can 
donate now! 

Updates on how funds are spent and lab results will be published on the U2FP 
website. Additional information from the researchers involved in the project 
will be presented at the Working 2 Walk 2012 Science and Advocacy Conference.  
<http://www.u2fp.org/organize/events/working-2-walk/> 


 
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