Jerry Silver and Other Discussion from ChinaSCINet Update

[paolocipolla]

Christopher,

What the authors found was that these NSAID's appear to block rho. Those results were very clear. I don't share Jerry's skepticism of all the results in the paper. Nor did the peer reviewers of the paper share his views. Finally, you should know that the most effective way to reduce stroke in people is a baby aspirin a day.

Wise.

Wise,

this post here above reminds me that in the past I had several times the impression that, sometimes, you don't fully realise the perspective of people living in chair.
For example, in this context, I don't see why did you say:
"Finally, you should know that the most effective way to reduce stroke in people is a baby aspirin a day" ?

It's more or less like if you go at W2W and give a presentation about preventimng stroke.. that is not exactly what the audience is interested in, who cares?

Anyway, don't worry, it has happened to me many times to listen to scientists talking to me about his/her wonderfull research and then I had to ask him/her "is that going to get me out of chair somehow"? Tipically the answer is "not really... bla bla" and the face of the individual turns red. If I don't see a red face in a few seconds then I usually ask something like "Why should I get excited hearing what you are telling me"?

Hope you understand what I mean and how bad people in chair may feel hearing researchers sometimes.

Paolo

[crabbyshark]

When axons approach the inhibitory environment, RhoA is activated in the axon.
When RhoA is activated in the axon, the axon freezes.
Evidence suggests that ibuprofen inhibits, or turns off, RhoA.

In turn, the inhibition of RhoA-activation blinds the injured axon to its growth inhibitory environment resulting in enhanced axonal sprouting and plasticity. This has been demonstrated in various CNS-injury models for direct RhoA-inhibition and for downstream/upstream blockade of the RhoA-associated pathway.

Axons regrow at ~1 mm per day.
Perhaps a dose of ibuprofen, or another similar NSAID, taken every day, would inhibit RhoA and allow regrowing axons to overcome the inhibitory environment in chronic SCI.

[ay2012]

These drugs have been determined to be safe for use in humans. Ibuprofen and its side effects are very well known. Ibuprofen is easily available. Time is of the essence. It should probably be put to clinical trial in acutes and chronics asap.

What?! Sorry but this is nonsense. Animal studies are significantly shorter than human trials. Every potential therapy (if possible) should be tested in a complete, chronic model before going to trial, in my opinion. Your view would only make sense if everything could go to trial collectively at the same time... Obviously the animal models wouldn't occur that way either, but a whole hell of a lot faster. If you want simply any therapy to go to trial, even if it hasn't demonstrated efficacy in a comparable animal model, I hope you're ready to sit through a bunch of failures or that you're ok with rolling the dice and waiting 5+ years per trial to even see what lands.

[cripwalk]

Wise,

this post here above reminds me that in the past I had several times the impression that, sometimes, you don't fully realise the perspective of people living in chair.
For example, in this context, I don't see why did you say:
"Finally, you should know that the most effective way to reduce stroke in people is a baby aspirin a day" ?

It's more or less like if you go at W2W and give a presentation about preventimng stroke.. that is not exactly what the audience is interested in, who cares?

Anyway, don't worry, it has happened to me many times to listen to scientists talking to me about his/her wonderfull research and then I had to ask him/her "is that going to get me out of chair somehow"? Tipically the answer is "not really... bla bla" and the face of the individual turns red. If I don't see a red face in a few seconds then I usually ask something like "Why should I get excited hearing what you are telling me"?

Hope you understand what I mean and how bad people in chair may feel hearing researchers sometimes.

Paolo

Please feel free to correct me if I'm wrong but Dr young's point was simply that a drug's usefulness shouldn't be dismissed because it is common, as it may have yet unexplored but effective alternative uses.

[GRAMMY]

We have not yet started the Cethrin experiments.

Wise.

A perfect opportunity to do a side by side comparison of Cethrin and aspirin in chronic rats!

[crabbyshark]

What?! Sorry but this is nonsense. Animal studies are significantly shorter than human trials. Every potential therapy (if possible) should be tested in a complete, chronic model before going to trial, in my opinion. Your view would only make sense if everything could go to trial collectively at the same time... Obviously the animal models wouldn't occur that way either, but a whole hell of a lot faster. If you want simply any therapy to go to trial, even if it hasn't demonstrated efficacy in a comparable animal model, I hope you're ready to sit through a bunch of failures or that you're ok with rolling the dice and waiting 5+ years per trial to even see what lands.

The specific combination UCBMC+MP+Lithium therapy, to my knowledge, wasn't tested in a chronic SCI animal model before being taken to trial in humans.

For a therapy to be tried in humans, the therapy simply has to be determined to be safe. It does not have to be determined to be efficacious. Failure is a part of learning. If it fails, it fails, but at least we know.

Ibuprofen is well known, cheap and easily available. There is evidence ibuprofen significantly helps animals when administered during acute spinal cord injury. The science behind the way ibuprofen affects axons suggests ibuprofen might be beneficial for those with chronic SCI.

It would be more than feasible to take 200 people with chronic spinal cord injury and split them up into two groups - placebo and ibuprofen, administer the medicine for 12 or 24 months, then determine if the ibuprofen group was any better than the placebo group at the end of the trial.

[ay2012]

The specific combination UCBMC+MP+Lithium therapy, to my knowledge, wasn't tested in a chronic SCI animal model before being taken to trial in humans.

For a therapy to be tried in humans, the therapy simply has to be determined to be safe. It does not have to be determined to be efficacious. Failure is a part of learning. If it fails, it fails, but at least we know.

Ibuprofen is well known, cheap and easily available. There is evidence ibuprofen significantly helps animals when administered during acute spinal cord injury. The science behind the way ibuprofen affects axons suggests ibuprofen might be beneficial for those with chronic SCI.

It would be more than feasible to take 200 people with chronic spinal cord injury and split them up into two groups - placebo and ibuprofen, administer the medicine for 12 or 24 months, then determine if the ibuprofen group was any better than the placebo group at the end of the trial.

This would still cost money. At the expense of possibly trying another therapy. I know that UCBMC weren't tested in a chronic animal setting. That's why people were justifiably weary beforehand, and skeptical still, but less so because they seem to be showing some results.

[crabbyshark]

This would still cost money.

Any trial costs money. Animal trials cost money. And time.

Ibuprofen is well-known. Once all the parameters were set, a clinical trial of ibuprofen would be far cheaper than a clinical trial of any therapy that includes expensive drugs or major surgery. If it works or not, we learn something. Either way, relatively little resources are expended finding out.

[Fly_Pelican_Fly]

Any trial costs money. Animal trials cost money. And time.

Ibuprofen is well-known. Once all the parameters were set, a clinical trial of ibuprofen would be far cheaper than a clinical trial of any therapy that includes expensive drugs or major surgery. If it works or not, we learn something. Either way, relatively little resources are expended finding out.

Good luck finding a principal investigator, the venture capital and a trial infrastructure for this incredibly awesome idea!

[jsilver]

Asking whether ibuprofen can provide any clinically relevant recovery after chronic spinal cord injury is like asking whether a squirt gun might have helped to put out the fires in the twin towers. Sure, the squirt guns would have helped.