Dr. Jan-Eric Ahlfors pushes forward with Regeneration Matrix

[Mize]

Just to be correct, complete and incomplete classifications are linked to residual sensory/motor outcomes rather than spared spinal cord tissue.

In the U.S. those terms are determined solely by sacral preservation. No anus sensation or function = complete even if you have other sensory and motor below the injury location.

[Nowhere Man]

Just to be correct, complete and incomplete classifications are linked to residual sensory/motor outcomes rather than spared spinal cord tissue.

Yes I know. My point is that it is (probably) well documented that rehab helps recovery with incomplete SCI. There is no proof that rehab helps regenerating axons reach functional targets because such recovery has never been achieved. I'm not saying it wouldn't be extremely helpful because I bet it would. I'm trying to point out that there is a reason why there is no proof yet...recovery after regeneration has never been achieved. Still at basic research stage, not human trial stage. Any substantial regeneration has been from neural stem cells shooting out axons, not the original axons in the animal's spinal cord. Unfortunately, its all just a clusterfck, with no recovery.

[Fly_Pelican_Fly]

Yes I know. My point is that it is (probably) well documented that rehab helps recovery with incomplete SCI. There is no proof that rehab helps regenerating axons reach functional targets because such recovery has never been achieved. I'm not saying it wouldn't be extremely helpful because I bet it would. I'm trying to point out that there is a reason why there is no proof yet...recovery after regeneration has never been achieved. Still at basic research stage, not human trial stage. Any substantial regeneration has been from neural stem cells shooting out axons, not the original axons in the animal's spinal cord. Unfortunately, its all just a clusterfck, with no recovery.

So what I think you're actually trying to articulate is that no lab has regenerated host corticospinal tracts in severe chronic animal models to restore motor function to a level close to that of pre-injury. This is factual. If you want to walk unaided, run, skip, hop, play the piano or play soccer again - yes basic science is still figuring it out.

However, recovery, even if not to a level of pre-injury is still worthwhile translating in the meantime. Recovery of some or even one autonomic function for example is absolutely huge and worthwhile investing in. In addition to this, the restoration of gross/crude function that could help you sit independently, reach, grasp, stand or even take a few clumsy steps will have absolutely massive impact on your independence and long term body integrity - bone health, muscle atrophy, skin health, metabolism and ageing.

Without doubt, basic science has some way to go to restore you to your full glory or even close to it, but there are enough lines of science to positively impact your body's function and integrity now. I think turning your nose up these efforts is a bit myopic.

The reality is the progress of the field is neither as great as some people make our nor as bad as some are painting it. It needs more money, more scientists that are not slaves to academia and importantly a business model that attracts investment.

[Mize]

Well said Pelican. Any amount of recovery represents a reduction in the suffering of the person with an SCI. I know, for a fact, that cervical-injury trial participants have regained use of arms and hands to a point of being able to use car hand controls. You're right that doesn't mean playing the piano well but to be able to drive is a massive change for the better.

[lunasicc42]

Well said Pelican. Any amount of recovery represents a reduction in the suffering of the person with an SCI. I know, for a fact, that cervical-injury trial participants have regained use of arms and hands to a point of being able to use car hand controls. You're right that doesn't mean playing the piano well but to be able to drive is a massive change for the better.

Which trial has restored hand function? (not doubting you, I am just not aware really)

[Nowhere Man]

So what I think you're actually trying to articulate is that no lab has regenerated host corticospinal tracts in severe chronic animal models to restore motor function to a level close to that of pre-injury. This is factual. If you want to walk unaided, run, skip, hop, play the piano or play soccer again - yes basic science is still figuring it out.

However, recovery, even if not to a level of pre-injury is still worthwhile translating in the meantime. Recovery of some or even one autonomic function for example is absolutely huge and worthwhile investing in. In addition to this, the restoration of gross/crude function that could help you sit independently, reach, grasp, stand or even take a few clumsy steps will have absolutely massive impact on your independence and long term body integrity - bone health, muscle atrophy, skin health, metabolism and ageing.

Without doubt, basic science has some way to go to restore you to your full glory or even close to it, but there are enough lines of science to positively impact your body's function and integrity now. I think turning your nose up these efforts is a bit myopic.

The reality is the progress of the field is neither as great as some people make our nor as bad as some are painting it. It needs more money, more scientists that are not slaves to academia and importantly a business model that attracts investment.

Actually, I am not trying to articulate that. I never said anything about recovery needing to be close to "pre-injury". Regeneration has never been proven to restore ANY function. It has never been proven to restore ANY sensation (probably impossible). It has never been proven to restore any voluntary use of muscle including bladder/bowel. Sure maybe some scientists have CLAIMED to achieve these things, but not in any published & replicated by reputable lab study.

[Jim]

Actually, I am not trying to articulate that. I never said anything about recovery needing to be close to "pre-injury". Regeneration has never been proven to restore ANY function. It has never been proven to restore ANY sensation (probably impossible). It has never been proven to restore any voluntary use of muscle including bladder/bowel. Sure maybe some scientists have CLAIMED to achieve these things, but not in any published & replicated by reputable lab study.

Our study documents concrete evidence of growth across the injury site and far beyond, return of walking, bowel, and bladder in ASIA A patients. Your statement is simply not true.

[Fly_Pelican_Fly]

Actually, I am not trying to articulate that. I never said anything about recovery needing to be close to "pre-injury". Regeneration has never been proven to restore ANY function. It has never been proven to restore ANY sensation (probably impossible). It has never been proven to restore any voluntary use of muscle including bladder/bowel. Sure maybe some scientists have CLAIMED to achieve these things, but not in any published & replicated by reputable lab study.

Regeneration is a loose term. Highlighting in bold wont give it more meaning. Which spinal tracts are you regenerating? Anything can fall into the term regeneration. What type of axon? What type of neuron? What type of function are you looking for?

You clearly have your own interpretation of what is means to you but it would be useful for readers to understand so please share in detail. Just citing axons migrating in, through and then out of the injury site and forming functional synapses is not really enough information to describe exactly what you are defining to be regeneration.

Just out of interest do you consider any of these regenerative?

http://www.pubfacts.com/detail/23804...nal-cord-injur
http://www.pubfacts.com/detail/22200...ions-for-regen
http://www.pubfacts.com/detail/26426...ndroitinase-In
http://www.pubfacts.com/detail/27019...l-regeneration

Also, why would you say restoring sensation is impossible? Is the data for the sensation change in the stem cell trial subjects to date a lie? These subjects have been independently assessed before and after intervention from what I understand.

[Nowhere Man]

Our study documents concrete evidence of growth across the injury site and far beyond, return of walking, bowel, and bladder in ASIA A patients. Your statement is simply not true.

a) it is not concrete evidence of regeneration. It can easily be spared intact axons and/or human error. DTI, from what I understand, highlights water movement, its not a picture of the axons. I'm pretty sure other contemporary scientists don't believe it is regeneration either. Isn't chinasci doing another trial right now, to see if untethering & locomoter training alone could be responsible for "walking".? Way too many questions remaining.
b) return of bladder? Can the patients feel urge of when they have to pee? Not AD, but actual sensation of bladder? Can the patients pee with brain thought alone? Tapping on your bladder is NOT return of bladder function. Its just using spinal cord circuitry. Not the brain. Didn't you say you have been managing your bladder for years by tapping? That's not having bladder function.
c) Describe the bowel function. What is your concrete evidence of return of bowel? Can the patients feel when they need to go? Can they go on command?

[Mize]

Which trial has restored hand function? (not doubting you, I am just not aware really)

My apologies.

I know someone in a clinical trial and had been under the impression it was responsible for their recovering hand function. After inquiring i have learned that was not the case. Arm and hand function had returned earlier.

[Nowhere Man]

Regeneration is a loose term. Highlighting in bold wont give it more meaning. Which spinal tracts are you regenerating? Anything can fall into the term regeneration. What type of axon? What type of neuron? What type of function are you looking for?

You clearly have your own interpretation of what is means to you but it would be useful for readers to understand so please share in detail. Just citing axons migrating in, through and then out of the injury site and forming functional synapses is not really enough information to describe exactly what you are defining to be regeneration.

Just out of interest do you consider any of these regenerative?

http://www.pubfacts.com/detail/23804...nal-cord-injur
http://www.pubfacts.com/detail/22200...ions-for-regen
http://www.pubfacts.com/detail/26426...ndroitinase-In
http://www.pubfacts.com/detail/27019...l-regeneration

Also, why would you say restoring sensation is impossible? Is the data for the sensation change in the stem cell trial subjects to date a lie? These subjects have been independently assessed before and after intervention from what I understand.

a) Well to me, to say the spinal cord regenerated means host spinal cord axons, the ones that were damaged upon injury (were "cut" via dieback or knife), have grown in the direction they are supposed to go. Sensory grows toward brain, movement grows down. It doesn't mean they grew back to original targets or even made any functional connections. To say regeneration, that to me would include things like neural stem cells where most of the axon regeneration is from neural stem cells and not host axons. I can't precisely define "substantial regeneration", I guess that's open for personal judgement. I know some treatments are only going to work on certain tracts. But if youre telling me a completely injured rat is walking again, that treatment had better restore tracts responsible for locomotion & sensation, which means long distance regeneration.


b) I'm not reading all those from Dr. Silver. Dr. Silver's treatment would be considered regeneration if true that host axons are growing through the bridge. I wouldn't use the term "robust" or "substantial" like he does. I'm not convinced that what they saw constitutes return of bladder function. Improved urodynamics does not equate to functional recovery. It might, but I'm not sure.

See figure 8.H. in "Nerve Regeneration Restores Supraspinal Control of Bladder
Function after Complete Spinal Cord Injury" by Dr. Silver.

2 millimeters? How robust. Am I reading this right. An average of 125 fibers made it 1 mm past graft site? 125 fibers? I must be reading this wrong maybe you can clarify that.

[Nowhere Man]

c) That study from Mark Tuczynski(sp.) looks like it came out this month. So you can forgive me for not knowing about it. I don't have access to the full paper. Once bitten, twice shy. I remember 4 years go, he came out with a study, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445432/ , which reported remarkable axon growth & recovery. "Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery."

But, when Dr. Oswald Steward’s lab went to replicate it, they couldn’t. Could they get neural stem cells to grow far, yes. But they couldn’t get host spinal cord axons to connect to them. Also, they couldn’t get any functional recovery. “There was extensive outgrowth of GFP labeled axons from the graft, but there was minimal ingrowth of host axons into the graft revealed by tract tracing and immunocy-tochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123968/

So, it will take a lot for me to regain trust in that lab. But it also goes to show that a study is not concrete proof. It needs to be replicated and even then things might not be what they seem.

[JamesMcM]

Actually, I am not trying to articulate that. I never said anything about recovery needing to be close to "pre-injury". Regeneration has never been proven to restore ANY function. It has never been proven to restore ANY sensation (probably impossible). It has never been proven to restore any voluntary use of muscle including bladder/bowel. Sure maybe some scientists have CLAIMED to achieve these things, but not in any published & replicated by reputable lab study.

I'm not a fan, but stem cell Inc. phase 1 trial with safety doses and no rehabilitation component showed and documented sensory improvement after their neural stem cell injection.

[JamesMcM]

My apologies.

I know someone in a clinical trial and had been under the impression it was responsible for their recovering hand function. After inquiring i have learned that was not the case. Arm and hand function had returned earlier.

I know what you're talking about, and it wasn't exactly a clinical trial, just a case study. There were other patients that showed upper body improvements though which is promising. Mind you none of these injuries were very chronic I think the latest was three years

[JamesMcM]

c) That study from Mark Tuczynski(sp.) looks like it came out this month. So you can forgive me for not knowing about it. I don't have access to the full paper. Once bitten, twice shy. I remember 4 years go, he came out with a study, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445432/ , which reported remarkable axon growth & recovery. "Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery."

But, when Dr. Oswald Steward’s lab went to replicate it, they couldn’t. Could they get neural stem cells to grow far, yes. But they couldn’t get host spinal cord axons to connect to them. Also, they couldn’t get any functional recovery. “There was extensive outgrowth of GFP labeled axons from the graft, but there was minimal ingrowth of host axons into the graft revealed by tract tracing and immunocy-tochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123968/

So, it will take a lot for me to regain trust in that lab. But it also goes to show that a study is not concrete proof. It needs to be replicated and even then things might not be what they seem.

This is just my opinion, it's pretty impressive that it "filled" the lesion as for no functional recovery I think that is because proper rehabilitation wasn't given. To cut cost little if any Was probably given. But technically they did replicate the results with substantial axon growth. I want to see high doses of neural stem cells injected at injury site directly, then the patient begins something like the Kumming walking program. Neural stem cells barn none are the superior cells for this issue. Just expensive, potentially dangerous, and difficult to harvest this is why am so interested in this clinical trial if they actually managed to reprogram bone marrow cells to neural. Of course everything is early, as we all know much more funding is needed for all of it