Posted tagged ‘Os Steward’

Let’s Review: Part One

November 15, 2012

I’m writing this from my desk at our house near Seattle . . . everyone who came to Working2Walk is by now long since home and settled back into whatever routines normally fill their days.  As I look over the posts on this blog, it occurs to me that there are a couple of things left to do.  One is to say thanks again to the people who worked all year to bring this thing into being, mostly as volunteers, one or two as very poorly compensated staff.  We owe them.

Another is to sift through all this information and highlight a few places that stand out for follow up and further review.  Your list might be different from mine on that score, and I’d be love to hear about it if that’s the case.  So, starting from the beginning . . .

1. Marilyn Smith’s words from her opening remarksWe have three tools. EDUCATE, ORGANIZE, and TAKE ACTION.  As those with the most skin in the game, we need to invest ourselves in the process.  The most powerful force we have going for us, though, is BELIEF.  We want you to leave this conference with belief in the power of science, knowledge, and advocacy.

2. Dr. Os Steward’s excitement about his CTRP team’s success in finding a specific gene — called PTEN — that blocks regeneration of nerves.  When someone with his reputation for calm and caution and meticulous communication 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 interested.

3. Dr. Murray Blackmore’s sheer cleverness, determination, and most especially, youth.  I’ve heard for a long time now that SCI research used to be considered a big fat dead end to any serious career.  “You’ll waste your life trying to solve that!  Focus on something that’s actually achievable!”  That was once common advice.  And here was this sharp new mind attacking the problems with impressive ingenuity and determination.  I especially liked the part where he said that he went data-mining in cancer research about transcription factors and quickly discovered that there are 210 of them that seem to have a role in cancer growth.  When he cross-checked that list of 210 with the 12 that he knew were involved with axon growth, 11 out of 12 were on the list.  As he told us, “That means the other 199 suddenly become very interesting . . . ”  In his talk, Blackmore described his just-published research that shows transcription factors can make old neurons think they’re young and still able to regenerate, so this matters.

4. Oy.  This is going to be a long list, I can see that.  I’ll put this up as part one and keep working on the rest.

Morning at the Reeve Irvine Research Center

November 3, 2012

Dr. Os Steward is describing how the place works . . . there are senior scientists, post grad fellowship people, grad students, technicians.

The technicians are all dressed up today, which they’re laughing about because most of the time they’re very much dressed down; one of them is talking now.

Her normal day is making rats pee, morning and night.  All our days are spent in the basement; we don’t see the sun much, don’t know what the weather is.  Every day of the year, no exceptions, because the animals need to be cared for.  An operation like this requires a LOT of people.

The plan for us today is to meet with the postdoc fellows, hearing about what they’re working on, getting a chance to ask them how what they’re doing is going to help US.  The grad students are the ones who are just starting their projects.  We’re going to see how labs work . . . from the cellular  level to animal models to human performance labs, where they’re looking at what kinds of rehab work best for people with impaired function.

He asks for questions, but we don’t know what to ask yet . . .

Kelly Sharp steps up to explain the logistics.  The senior scientists will be arranged around the various labs, ready to explain and take questions as needed.  We’re free to roam around and see what there is to see for about an hour and a half, then come back to eat.  They’ve set up their most intriguing equipment so that we can see what it is and how it works.

Hmmmm.  Not sure how I’m going to do this blog thing in that scenario.  Probably go around and find the most crazy-interesting things & try to describe as we go.

Some background — Reeve Irvine Research Center got started because an elderly woman with a lot of money and a love of horses saw Chris Reeve being interviewed on television not long after his injury.  She was touched and impressed that he didn’t blame the horse, and she sent him a note volunteering to hand over a million dollars to establish a center here.  The story is that Dana and a friend were opening the piles of mail and came across that note, almost dismissing it as impossible.

But here we are.  It’s a 4-story building that’s obviously built for access.  Off we go.

Os Steward

November 1, 2012

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.