UC Irvine - hav we all seen this one?

[Christopher Paddon]

http://today.uci.edu/news/2010/08/nr_pten_100808.php

[mamadavid]

Comments from Dr Young, Dr Silver?

The article seems to be more than a year old, yet it appears on the November 17 issue. Has anyone heard any more recent news about it?

[paolocipolla]

This is the evolution, even more exciting IMO
Sustained axon regeneration induced by co-deletion of PTEN and SOCS3

.....Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration...

http://www.nature.com/nature/journal...ture10594.html

[lakboy]

Here goes , the only trial for chronic spinal cord injury is the one that Dr. wise is doing , and if that fails then forget about a cure for at least ten years and here I am being optimistic.

[GRAMMY]

Here goes , the only trial for chronic spinal cord injury is the one that Dr. wise is doing , and if that fails then forget about a cure for at least ten years and here I am being optimistic.

Check out the chart for spinal cord injury clinical trials here...China is not the only one with a trial.

unite2fightparalysis.org/clinicaltrials

[kbailey]

PTEN activity is low early during development, allowing cell proliferation. PTEN then turns on when growth is completed, inhibiting mTOR and precluding any ability to regenerate.

Would that mean that an infant who suffers a spinal cord injury is less likely to become paralyzed????

[dr.zapp]

For my thoughts on why pten is a poor target for SCI therapy any time soon- /forum/showthread.php?t=148545&page=2

As a side note, Dr He's lab that did this is in the middle of moving to UCSD from Harvard so they can take advantage of the better research environment for stem cells in California.

[kbailey]

Don't get all excited about this, as I said in my earlier post- PTEN is a tumor suppressor! You take it away and you get cancer.

So same thought different question, why aren't infants more susceptible to cancer?

[Bob Yant]

Neurons are not susceptible to cancer-like growth. Glial cells are what causes brain cancer. pTEN inhibition causes the axons to regenerate from the neuron cell body.

Dr. He is moving to UC Berkeley, not UCSD. Dr. He is not moving to California because of the better research environment for stem cells in California.

[paolocipolla]

For my thoughts on why pten is a poor target for SCI therapy any time soon- https://www.carecure.net/forum/showt...=148545&page=2

As a side note, Dr He's lab that did this is in the middle of moving to UCSD from Harvard so they can take advantage of the better research environment for stem cells in California.

In the abstract I read:

"Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery"

http://www.nature.com/nature/journal...ture10594.html

I wonder if there could be a way to activate mTOR and STAT3 without co-deleting PTEN and SOCS3?

Then if that would be possible would still exist the cancer risk?

Paolo

[paolocipolla]

Neurons are not susceptible to cancer-like growth. Glial cells are what causes brain cancer. pTEN inhibition causes the axons to regenerate from the neuron cell body.

Dr. He is moving to UC Berkeley, not UCSD. Dr. He is not moving to California because of the better research environment for stem cells in California.

Thank you Bob for providing these info.

So now I wonder how would be possible to inhibit PTEN just in the neurons?

I guess they are working on that..

Paolo

[dr.zapp]

Neurons are not susceptible to cancer-like growth. Glial cells are what causes brain cancer. pTEN inhibition causes the axons to regenerate from the neuron cell body.

Dr. He is moving to UC Berkeley, not UCSD. Dr. He is not moving to California because of the better research environment for stem cells in California.

Whoops, just had heard that from a post doc that is in the same Dept, guess his info was less than accurate. What is your connection w/ Dr. He?

Neruons do form tumors, just not very common (abt 1%)... central nerocytoma, gangliocytoma, dysplastic cerebellar gangliocytoma, ganglioglioma, desmoplastic infantile ganglioglioma, dysembryoplastic neuroepithelial tumor, ganglioneuroma... but then again, a pten deletion/inhibition is not very common either, so who knows what will happen after a few years post-treatment. On a good note- neuronal tumors are much more treatable than gliomas, often just require surgery... but if it is unresectable, still not good.

[Wise Young]

The article seems to be more than a year old, yet it appears on the November 17 issue. Has anyone heard any more recent news about it?

Dr. He is the senior author on a paper published by my former graduate student Kai Liu, who showed that knocking out PTEN in mice strongly stimulates corticospinal tract regeneration. This study showed that the importance of genetic control of growth. CNS axons of course once grew during development but genetic stimulation of such growth turns off during development. It seems that PTEN is part of the mechanisms that stops axonal growth, acting through downstream mechanisms such as mTOR.

This is the first time that I have heard STAT3 being proposed to be a major factor. We recently published a paper in PLOS ONE, showing the lithium inhibits astrogliogenesis by inhibiting STAT3. Of course, lithium stimulates regeneration of spinal tracts probably by stimulating NFAT and WNT/beta-catenin. There are some suggestions that lithium also acts by up regulating mTOR but all these still need to be studied. The reason why we are using lithium is because it facilitates regeneration and neurotrophin production by stem cells.

Dr. He is moving from Harvard to UC Berkeley. He will be doing so in January. It is s significant loss to Harvard and a great addition to Berkeley.

Wise.

[Bob Yant]

Last week Zhigang He had an article published in Nature online, showing that blocking both SOCS3 and pTEN led to a ten fold regeneration in the optic nerve compared to pTEN inhibition alone.

http://www.nature.com/nature/journal...ture10594.html