Jerry SilverPosted: October 17, 2014
It wouldn’t be working 2 walk without Jerry.
Talk is called Update on Experiments to Restore Function after Chronic SCI
Background . . . his Ramon Cajal drawing showing how axons die back after injury. Cajal thought the axons died. He was wrong. The axons are alive, they’re sitting in the white matter of the cord, waiting.
They’re trapped. Why?
Oh, and his cartoons that show the possible reasons. Not going to type this all out, because you can see it for yourself. Recommend going to watch this video from 2012, where you can see all of this introductory material yourself. It’s worth your time. Really. Or, if you have the 2012 book you can read the chapter about Jerry’s peptides and how they break down the environment that keeps axons from growing.
Still going over the peptide stuff, the first one of which was identified in his lab in 2009. These receptors are so interesting. It turns out that the receptors are like flypaper to axons . . . you get a bunch of them together and the axons can’t help themselves . . . they grow into it and never come out. What the peptides do is allow the axons to move through the injury site.
So they did their injuries to the rats. And in the acute rats, it worked very well. 21 out of 26 animals treated with the ISP peptide got some recovery. 3 of those recovered essentially fully.
They looked at what would happen if they increased the dose by a factor of 4 — and that made every single animal recover bladder function. When they looked at the slides, they saw that there wasn’t axon growth from the brain and past the injury, but there was a big jump in growth below the injury.
What about chronics? They damaged the rats. Then they waited for 2 months (which is a chronic phase for rats). Then they added chABC, and FGF (growth factor) and picked the scar, which he says is like cellophane, then they built a little bridge. And then they waited for 7 or 8 months.
They saw some kinds of nerve growth, but not all. Not serotonergic. Have not yet seen improvements in locomotion.
Okay, bummer. They need the serotonergic neurons. Why aren’t they growing? It looks like there’s a gene that needs to be turned off. It’s called SOCS3. So they turned it off and saw the peeing behavior improve quite a lot, but not the locomotion.
Gah, okay. Still need to mess with these poor rats all over again.
But maybe they don’t have to build a bridge at all . . . took a new group of injured rats. Waited 6 months. Injected ChABC, injected peptides. There were 10 animals at the start, but staying alive with injuries this severe is very difficult, and only 4 of them made it to the final part of the testing.
And one of those four was absolutely a superstar. (It’s hard to feel enthusiastic about rat recovery. It is.) And yet I can see that Jerry himself is feeling pretty enthusiastic . . . I mean he got a seriously damaged chronic animal to recover almost fully, and without needing to build bridges or rearrange genes.
They only did simple injections, remember.
Next . . . assemble a world class team to do combinations that will pull together what we know is working. Peptides, chABC, rehab, genes. That’s the agenda over the next few months.
One thing that occurs to me is that if it’s that difficult to keep chronic rats alive, we have a problem. We