Breakout Two: Jerry Silver

It took one year to figure out how to deal with the chronic spinal cord . . . I have a courageous collaborator in my lab who I’ll introduce tomorrow.  I say, with respect to chronic or acute, just do the chronic.  Every lab that has a robust result, you should be doing it.

That’s why the w2w organizers chose us to be here, because they knew we were doing it.

Also, at NIH they’re dying to see work related to chronic . . . (well, that’s good news.)

Jerry on the chronic cord: axons that were cut have died back . . . there’s a dense wall full of stem cells surrounding the lesion with a moat of nothing in between.  They can sit there for decades.  That very dense scar has to be removed.  If you can take advantage of plasticity with locomotor training; and there are things (optigenetics) that work only in the beginning.

What’s going on in the cord is good and bad.  Good = nerves are still there.  Bad = things are getting reorganized in nonfunctional ways.  BUT the abnormal circuitry can be fixed with lots of therapy.  In the case of the respiratory system, just chondroitinase (ChABC) restores the proper function.

What happens if we just knock out p10 (the gene Os talked about earlier this morning)?  We might get chaotic new circuitry . . . that’s one of the things we’re testing to see.  We’re doing that right now.  In chronics.  

We have a whole variety of lesion models, from hemisections to removal of a whole section of the cord to contusions.  Contusions are the bloodiest, and therefore the biggest.  Jerry’s saying that he thinks the scar after injury is just a mistake — just a mistake.

What kind of animal would recover the fastest with a transection?  No warm-blooded species can regenerate any function with a complete transection . . . but an embryo does have more plasticity and can recover better from a partial transection.

What about those animals that didn’t recover in your lab?  All of our work is double blind, and we’ve done the work 3 separate times, so I know it’s not a fluke.  We try to do all the injuries exactly the same, then using the doses that worked well in tissue culture, and we saw the variability you heard about this morning.  Some got a lot of walking back, some got none at all.  Some got urination, some got none.  Some got both, some got neither.  Why?  Maybe the injuries are not exactly the same.

Okay, talk about the beach chair . . . what is that?  After injuries, there are OPCs, ependymal cells, a whole mixed bag of stem-like cells hanging out in that space around the lesion.  As soon as the axon is cut, it dies back a little bit, and then macrophages come in and drive those nerve cells back.   This is inflammation.

Stopping the inflammatory process would be a good thing, eh?  The stem cell population LOVES the core of the lesion; the axons HATE it.  So the stem cells have it all to themselves . . . as the axons go backwards, they see more and more of those stem cells, which make a rich cocktail of things, including the NG2 proteoglycan.  That’s the beach chair.  Ng2 Gleos normally make synapses.  These are glial precursors.  They depolarize.  They’re sampling the brain, looking for dead oligodendrocytes.  In the injured cord, they’re still doing that, but they’re in the wrong place.

Q: Doesn’t that mean that the Geron study was adding more to what was already there, doing harm?  Well, same cells but they were putting them all around the outside, hoping they’d remylenate the stripped axons outside the lesion site.

Q:  Who are the young guns that are going to replace you?

We’re always training new students; several from Os’s lab are right here.  Also I’m not dead yet! (laughter)

Q: Where’s the peptide thing going?

What’s really important to go forward is a robust result.  You don’t need a little tick in a graph.  You need something big.  My university got all excited about this and wrote a patent, which they’re now shopping around, and we’re now in our fourth round of discussions with GlaxoSmithKline, though they want it for stroke and other things.  Once they get it, we lose control.  They can do whatever they want, and sci is not going to be high on their list. Jerry says he won’t sign any contract without something in it for SCI patients.

This community can influence that process if WE MAKE A LOT OF NOISE.

Martin puts out a thought experiment . . . why do we rely on pharma at all?  They’re not there to help us.  We need to be like the AIDS community was — we can raise money ourselves, independently.  They’ll make viagra 4 or something, a better boner medicine. (laughter)

Back to stem cells . . . are those things proliferating, reproducing, what the heck are they doing?  They’re everywhere, like tiles.  NG2s . . . they make myelin.  They respond to the wound by dividing. The core of a lesion is full of them, stuck.  If you clean the scar, you’re damaging those tips — which may be good — you may be starting them up again.

(Oy, I need pictures with arrows and circles to understand this better.)  He’s talking about synapses as if they were little magnetic zones.

Can anything be done by US to get rid of scar?  No.

Break to post.  More in a sec.

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One Comment on “Breakout Two: Jerry Silver”

  1. […]  Dr Steward saying that if there were $1 Billion, the Manhattan Project would happen.  Dr. Silver saying that his lab is working on chronics, and that he thinks everybody who has a robust result […]

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