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. Dr. Silver can be seen here on an interactive presentation.
U2FP has established a Research Fund to support this exciting 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. You can donate now!
Updates on how funds are spent and lab results will be published on the U2FP website. Additional information and updates from the researchers involved in the project will be presented at the Working 2 Walk 2012 Science and Advocacy Conference.