Os Steward

I can’t think of anyone I’d rather have introduce me . . . Bob has been a wonderful friend for many years & has helped us in so many ways, some of which you’ll be hearing about this morning.

For those of you who don’t go to a lot of meetings, you need to know that this one is really quite special.  For those who aren’t scientists, please put us on the spot, ask us questions, that’s why we’re here.

Image of the RIRC staff on the screen, where 80 people now work on nothing but curing spinal cord injury.

For the first time, we’ve been able to achieve the holy grail of regenerative research.  In the past three years, lots of labs working around the world and collaborating together have solved one of the hardest puzzles.  Points out one in particular, Minoru Fujiki . . . says the guy flies in, works all day, gets back on a plane and flies home.

Goal to develop a therapy to induce regeneration of the pathway that controls movement after sci — they’re focused on the Corticospinal Tract, hence the name of their project CSTP.  There’s been little success until just the last couple of years.  They’ve succeeded.  Showing an image from an MRI.  The usual.  Axons in red, stopped dead at the lesion site.  New image, but this time the axons have grown past the injury.

It’s a rodent, eh?  What if you could do it in a person?

This is 2-3 segments worth of growth . . . showing a chart of possible daily activity for C4 vs C6 . . .we all know what this means.  Making a c4 injury into a c6 one would be huge.

One reason regeneration does not occur is that molecular pathways that could mediate regeneration are shut down.  One of those pathways is known as mTOR, which is shut off by a molecular brake called phosphatase and tensin inhibitor PTEN.  Blocking PTEN restores the ability to regenerate nerve connections after spinal cord injury!  

(That exclamation point is on the screen, it’s not my addition.)

The proof of concept paper was from Kevin Park in 2008, Science 322.

So they did the work on the spinal cord.  Deleting pten allows regeneration in the cord.  Published in nature neuroscience

(break while they try to adjust the color on the laptop for his slides . . . technology is awesome when it works.)

They did the work on mice because they’re convenient . . . but they don’t have the kinds of cavities that happen in rats and humans.  There was always going to be another problem to solve.  They wanted to move to a better model — one that had scarring.

Steps to Translation (meaning, getting a therapy to human beings)

1. show that regrowing axons lead to better function

2. knock out the pten gene in a therapeutically relevant time frame — meaning, in their experiments so far they’ve knocked it out first, then inflicted the sci, then watched the axons grow across the injury site . . . they’re now testing for what happens if the pten gene is knocked out after the injury . . . they expect it will have the same result, but it has to be shown.

3. come up with a workable delivery system for humans

They think they’ve done it . . . a tentative yes.

So, what are they working on now . . . a crush cervical injury given to a rat.  What’s the best way to test for functional recovery?  They made a little slanted platform with stepped up buckets of pellets.  The rat has to reach down further and further to get a pellet.  The deepest well is hardest to get to . . . but their pten treated rats could do it, if they also had something called Fibrin.

This intervention was shortly after the lesion . . . are we going to hear about chronics?  Most definitely.

It’s not NO . . . it’s really, truly JUST MAYBE.

There is a lot more to do . . . especially in working out the details of delivery.

So, how much recovery might be possible?  That’s unclear.

An open question is how this scales up . . . he’s showing an image of human, rat, and mouse brain/cord laid side-by-side.  the human one is a lot bigger.

Okay.  Thank you very much.

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2 Comments on “Os Steward”

  1. Clearly they are working out the Pten for acutes and chronics will be left behind… I have seen this attitude too many times… they marginally mention chronic to keep us calm, but that’s a joke.. Problem is that to run a clinical trial for acute takes much longer and many more patients.. etc.. if they don’t want to seriously target chronics we need to cut their founding! that’s all they understand.

  2. […] shows enthusiasm, it’s definitely catching.  I’ve gone back and put some links into that post so you can read the background material yourself if you’re […]

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