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    Originally posted by jsilver View Post
    "Are you aware that neither chondroitinase nor PTEN deletion has been shown to restore function after spinal cord contusion?"


    Sorry Wise, You're wrong again.
    Jerry, I am sorry that you commented on the post before I had a chance to complete editing it. I was referring to chronic spinal cord contusion. Tony Caggiano's study studied a crush/compression model of the spinal cord and up to two weeks. I know that they called it contusion but it is a crush/compression and not a contusion model. In the Iseda study, we looked at the effects of chondroitinase up to 4 weeks and saw no regeneration after contusion. However, we saw regeneration in the hemisection model.

    Wise.
    Last edited by Wise Young; 24 Jun 2012, 12:34 PM.

    Comment


      Chondroitinase

      Jerry,

      Let me expand the discussion about chondroitinase therapy of spinal cord injury. I am very aware of the work by Tony Caggiano. As you know, I was on the Board of Directors of Acorda Therapeutics when that study was done in the company. I know that Tony called it contusion model but I believe that it is a crush/compression and not a contusion model which requires rapid indentation with velocities of >0.1 m/sec. In any case, they studied the effects of chondroitinase only up to 2 weeks after injury, found locomotor and bladder improvements but did not evaluate corticospinal tract regeneration in the animals.

      Only several studies have been published concerning chondroitinase effects on locomotor recovery after severe spinal cord contusion and most have been negative. Jakeman, et al. [1] showed that a single intraparenchymal injection of chondroitinase ABC (ChABC) did not improve walking in mice when given 7 days after injury. Harris, et al. [2] showed that ChABC enhances peri-contusion axonal sprouting and did not confer “robust improvements in behavioral recovery”.

      In contrast, many researchers have reported significant functional recovery in animals treated with ChABC shortly after hemisections [4-9]. As you know, such partial injuries of the spinal cord leave many residual axons that can sprout to enhance function. Transected spinal cords tend not to regenerate because of the gap between the two stumps. Thus, it would seem that the most appropriate spinal cord model to test chondroitinase is the chronic severe spinal cord contusion model produced by at 25 mm 10g weight drop contusion, the animal equivalent of an ASIA A spinal cord injury.

      In the 2008 Iseda study [3], we tried to fill in the gaps in the Caggiano, et al. study by looking for effects of chondroitinase applied as late as 4 weeks after contusion injury or hemisection. We found no corticospinal tract regeneration or walking recovery in contused rats treated up to four weeks after injury. However, we did saw corticospinal tract regeneration and walking recovery in the hemisection model.

      Combinations of ChABC with other therapies seem to enhance ChABC ability to promote recovery. For example, Lee, et al. [10] found that L1 and chABC applied late promoted recovery after spinal cord compression injury in mice. Tom, et al. [11] removed necrotic tissue at a cervical contusion site, placed a peripheral nerve graft, and treated with GDNF and ChABC to promote some functional recovery. Combination of ChABC with clenbuterol [12], peripheral nerve bridges [13-15], Schwann cell bridges [16], neurotrophins [17, 18], and lithium [19] markedly enhanced the ChABC effects in various spinal cord injury models.

      Would you advocate applying ChABC alone to chronic ASIA A spinal cord injuries in humans without further animal experimentation? Would you support a clinical trial giving ChABC to chronic incomplete (ASIA B & C) spinal cord injuries? Which would you prefer to give: cethrin or ChABC? Would you favor doing a combination therapy and, if so, which?

      Wise.

      References Cited

      1. Jakeman LB, Hoschouer EL, Basso DM. Injured mice at the gym: review, results and considerations for combining chondroitinase and locomotor exercise to enhance recovery after spinal cord injury. Brain Research Bulletin. 2011;84(4-5):317-26. [PMID: 20558254]
      2. Harris NG, Mironova YA, Hovda DA, Sutton RL. Chondroitinase ABC enhances pericontusion axonal sprouting but does not confer robust improvements in behavioral recovery. J Neurotrauma. 2010;27(11):1971-82. [PMID: 20809786]
      3. Iseda T, Okuda T, Kane-Goldsmith N, Mathew M, Ahmed S, Chang YW, Young W, Grumet M. Single, high-dose intraspinal injection of chondroitinase reduces glycosaminoglycans in injured spinal cord and promotes corticospinal axonal regrowth after hemisection but not contusion. J Neurotrauma. 2008;25(4):334-49. [PMID: 18373483]
      4. Carter LM, McMahon SB, Bradbury EJ. Delayed treatment with chondroitinase ABC reverses chronic atrophy of rubrospinal neurons following spinal cord injury. Exp Neurol. 2011;228(1):149-56. [PMID: 21215745]
      5. Jefferson SC, Tester NJ, Howland DR. Chondroitinase ABC promotes recovery of adaptive limb movements and enhances axonal growth caudal to a spinal hemisection. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011;31(15):5710-20. [PMID: 21490212]
      6. Tester NJ, Howland DR. Chondroitinase ABC improves basic and skilled locomotion in spinal cord injured cats. Exp Neurol. 2008;209(2):483-96. [PMID: 17936753]
      7. Cafferty WB, Bradbury EJ, Lidierth M, Jones M, Duffy PJ, Pezet S, McMahon SB. Chondroitinase ABC-mediated plasticity of spinal sensory function. J Neurosci. 2008;28(46):11998-2009. [PMID: 19005065]
      8. Yick LW, Cheung PT, So KF, Wu W. Axonal regeneration of Clarke's neurons beyond the spinal cord injury scar after treatment with chondroitinase ABC. Exp Neurol. 2003;182(1):160-8. [PMID: 12821386]
      9. Yick LW, Wu W, So KF, Yip HK, Shum DK. Chondroitinase ABC promotes axonal regeneration of Clarke's neurons after spinal cord injury. Neuroreport. 2000;11(5):1063-7. [PMID: 10790883]
      10. Lee HJ, Bian S, Jakovcevski I, Wu B, Irintchev A, Schachner M. Delayed Applications of L1 and Chondroitinase ABC Promote Recovery after Spinal Cord Injury. Journal of Neurotrauma. 2012. [PMID: 22497349]
      11. Tom VJ, Sandrow-Feinberg HR, Miller K, Santi L, Connors T, Lemay MA, Houle JD. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(47):14881-90. [PMID: 19940184]
      12. Bai F, Peng H, Etlinger JD, Zeman RJ. Partial functional recovery after complete spinal cord transection by combined chondroitinase and clenbuterol treatment. Pflugers Archiv : European journal of physiology. 2010;460(3):657-66. [PMID: 20552220]
      13. Cote MP, Hanna A, Lemay MA, Ollivier-Lanvin K, Santi L, Miller K, Monaghan R, Houle JD. Peripheral nerve grafts after cervical spinal cord injury in adult cats. Exp Neurol. 2010;225(1):173-82. [PMID: 20599980]
      14. Houle JD, Amin A, Cote MP, Lemay M, Miller K, Sandrow H, Santi L, Shumsky J, Tom V. Combining peripheral nerve grafting and matrix modulation to repair the injured rat spinal cord. Journal of visualized experiments : JoVE. 2009(33). [PMID: 19935638]
      15. Houle JD, Tom VJ, Mayes D, Wagoner G, Phillips N, Silver J. Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord. J Neurosci. 2006;26(28):7405-15. [PMID: 16837588]
      16. Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD. Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci. 2005;25(5):1169-78. [PMID: 15689553]
      17. Liu T, Xu J, Chan BP, Chew SY. Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair. Journal of biomedical materials research Part A. 2012;100(1):236-42. [PMID: 22042649]
      18. Karimi-Abdolrezaee S, Schut D, Wang J, Fehlings MG. Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury. PLoS ONE. 2012;7(5):e37589. [PMID: 22629425]
      19. Yick LW, So KF, Cheung PT, Wu WT. Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. Journal of Neurotrauma. 2004;21(7):932-43. [PMID: 15307905]
      Last edited by Wise Young; 24 Jun 2012, 2:16 PM.

      Comment


        Dr.Wise, thanks a lot for this elaboration, and I have a question: does clenbuterol supposed to act here as a provider of cAMP for adrenalin intracellular spreading? May you specify what are the "various spinal cord injury models"?

        Comment


          Wise,

          I spent this morning re-reading your (Iseda et al) J Neurotrauma paper so I can directly address some of your questions and speculate on the answers to others. Firstly, I suggest again that you carefully define “sprouting” as axons stemming from remaining axons versus “regeneration” which is axons arising from previously cut axons. In my opinion you should use the word “regeneration” much more sparingly. It is quite clear that you cannot and should not claim that there was CST regeneration mediated via ch’ase in your hemisection model because you did not serially reconstruct axons back to their origins. It is impossible to rule out sprouting from spared fibers, which is what likely occurred. Fiber sprouting of a number of supraspinal axon systems mediated via ch’ase with reproducible functional recovery has been demonstrated time and time again by many other labs. Importantly, nobody has shown significant “regeneration” of CST axons after a single injection of ch’ase in any model. I would also add that nobody has convincingly demonstrated regeneration of CST axons using stem cells or lithium. Also, it is clear that frank regeneration of CST axons after severe contusive injury has not occurred in any lab after a single injection of ch’ase. Given the magnitude of tissue damage and axon loss with contusive injury, a single injection of ch’ase has had at best minor effects and we will need additional strategies to bridge such lesions (see below). Liz Bradbury is the first to present data recently that the application of a long lasting and widespread lenti viral delivery of ch’ase following severe contusive injury can lead to CST sprouting (among other fibers systems) and restore modest locomotor function. I could not find any behavioral experiments in the Iseda paper, so where is the walking data you were talking about? Importantly, we are using PNS grafts and ch’ase to bridge even more serious, complete thoracic transection lesions and we have now shown for the first time that substantial, centimeters-long regeneration of TH, 5-HT and propriospinal axons can occur with impressive return of urinary function. However, there was no evidence of CST or rubro-spinal tract regeneration. There was a modest improvement in locomotor behavior (BBB score of 2 to 7) which was likely mediated via the regeneration of the catecholaminergic projections (the paper is in review at Neuron). In terms of chronic spinal cord injury, we have recently shown impressive return of respiratory function 1.5 years after C2 hemisection lesion following a single injection of ch’ase at C4. The magnitude of functional recovery is far greater (by 4 fold) than that which occurs at acute stages. This is a fascinating discovery that we are still trying to understand. The result gives great hope to the SCI community. Importantly, our new chronic data along with that from the James Fawcett lab of a positive ch’ase effect on forepaw function in a chronic cord injury model has stimulated great interest from the International Spinal Research Trust (ISRT in England). I am very pleased and excited that serious talks about clinical trials are ongoing. Questions about which patients would best benefit from ch’ase administration; where, when and how much enzyme is to be delivered: ( the enzyme will likely be delivered well below the injury level rather that at the site of injury) and the role of rehab are all now being discussed

          Comment


            Wow, great to be able to participate (by watching). Thanks, Dr. Young and Dr. Silver.

            Comment


              Originally posted by kivi66 View Post
              Dr.Wise, thanks a lot for this elaboration, and I have a question: does clenbuterol supposed to act here as a provider of cAMP for adrenalin intracellular spreading? May you specify what are the "various spinal cord injury models"?
              kivi66,

              The abstract for the clenbuterol and chondroitinase paper is attached. Clenbuterol is an alpha adrenergic agonist and activation of that receptor increases cAMP, which has been shown by Marie Filbin and Pearce and Bungle, et al. to stimulate regeneration in the spinal cord. That presumably is the mechanism of the synergistic effects of the two treatments together.

              Regarding "various spinal cord injury models", I was referring to the various ways that people cut the spinal cord, i.e. lateral hemisection, dorsal hemisection, overhemisection, etc. to produce an incomplete injury with large numbers of residual axons crossing the injury site. Chondroitinase should increase sprouting of these residual axons to reconnect with more neurons and thereby improved function without regeneration.

              Note that animals should recover locomotion from hemisections and partial sections of the spinal cord. Thus functional recovery is usually not significantly different between chondroitinase treated and control untreated animals. That is why I did not describe these models any further because they are not particularly useful for showing functional regeneration. Most of the successful use of chondroitinase to treat spinal cord injury have used these incomplete injury models.

              Wise.

              [*] Bai F, Peng H, Etlinger JD and Zeman RJ (2010). Partial functional recovery after complete spinal cord transection by combined chondroitinase and clenbuterol treatment. Pflugers Archiv : European journal of physiology 460: 657-66. Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA. Spinal cord injury not only disrupts axonal tracts but also causes gliotic, fibrotic, and Schwannotic scarring with resulting deposition of chondroitin sulfate proteoglycans (CSPGs) which prevent axonal reconnection and recovery of locomotor function. Here, we determined whether recovery of locomotor function could be promoted after complete transection, by degrading CSPGs enzymatically within the injury site with chondroitinase ABC (chABC) together with treatment with the beta(2)-adrenoceptor agonist, clenbuterol, a neuroprotective agent which can promote regrowth of lower motoneurons. Partial recovery of locomotor function was observed 8-12 weeks postinjury only after combined chABC and clenbuterol treatment. The recovery of locomotor function coincided with the presence of axons caudal to the injury site arising from neurons of the reticular, vestibular, and red nuclei also only with combined chABC and clenbuterol treatment. Axons myelinated by Schwann cells were most prominent in the transection site in the combined treatment group. Clenbuterol treatment activated cAMP response element binding protein within retrogradely traced neurons which has been associated with axonal regrowth. ChABC treatment decreased scarring due to both CSPG and collagen deposition as well as the gap between intact regions of the spinal cord. ChABC also increased numbers of phagocytic cells which remove myelin debris as well as populations of astrocytes thereby aiding blood-spinal cord barrier reformation. Together the results suggest that chABC and clenbuterol can act synergistically to promote recovery of locomotor function.

              Comment


                Jerry,

                Thanks very much for reviewing the paper. I agree with most of what you say. I don't mind using the term "sprouting of residual axons" to refer to growth of axons that remain at the injury site. Our colleagues may object to changing the definition of "sprouting" since many use the word sprouting to refer to regrowth of cut axons.

                I think that Iseda did see regrowth of corticospinal axons in chondroitinase treated rats. He labeled corticospinal axons by injecting dye into the motor cortex and he saw labeled axons crossing the injury site in chondroitinase-treated rats while there were none in hemisected rats that were not treated with chondroitinase. There are few ways to explain this other than regeneration.

                I agree with you that "frank regeneration" of corticospinal tracts across contusion sites has not been reported. We did not see such regrowth after chondroitinase treatment, even though injection of chondroitinase dramatically reduced immunoreactivity to CSPG within 4 days and CSPG immunoreativity remained low for at least 3 weeks after.

                As you can imagine, Iseda was surprised by this finding. One possibility is of course that the CSPG immunoreactivity is gone but part of the CSPG is still there inhibiting axonal growth in the contusion model and not hemisection model. I hope that you would agree that this is unlikely. By the way, it is true that the paper did not show any walking data. However, if chondroitinase did restore walking in rats with contusion injuries, we would have been very glad to have seen and reported it.

                For people who might be interested in the paper, I attach a copy of the reprint. I will comment on the other aspects of your post later (I have to pack to leave tomorrow to get back to the U.S.).

                Wise.



                Originally posted by jsilver View Post
                Wise,

                I spent this morning re-reading your (Iseda et al) J Neurotrauma paper so I can directly address some of your questions and speculate on the answers to others. Firstly, I suggest again that you carefully define “sprouting” as axons stemming from remaining axons versus “regeneration” which is axons arising from previously cut axons. In my opinion you should use the word “regeneration” much more sparingly. It is quite clear that you cannot and should not claim that there was CST regeneration mediated via ch’ase in your hemisection model because you did not serially reconstruct axons back to their origins. It is impossible to rule out sprouting from spared fibers, which is what likely occurred. Fiber sprouting of a number of supraspinal axon systems mediated via ch’ase with reproducible functional recovery has been demonstrated time and time again by many other labs. Importantly, nobody has shown significant “regeneration” of CST axons after a single injection of ch’ase in any model. I would also add that nobody has convincingly demonstrated regeneration of CST axons using stem cells or lithium. Also, it is clear that frank regeneration of CST axons after severe contusive injury has not occurred in any lab after a single injection of ch’ase. Given the magnitude of tissue damage and axon loss with contusive injury, a single injection of ch’ase has had at best minor effects and we will need additional strategies to bridge such lesions (see below). Liz Bradbury is the first to present data recently that the application of a long lasting and widespread lenti viral delivery of ch’ase following severe contusive injury can lead to CST sprouting (among other fibers systems) and restore modest locomotor function. I could not find any behavioral experiments in the Iseda paper, so where is the walking data you were talking about? Importantly, we are using PNS grafts and ch’ase to bridge even more serious, complete thoracic transection lesions and we have now shown for the first time that substantial, centimeters-long regeneration of TH, 5-HT and propriospinal axons can occur with impressive return of urinary function. However, there was no evidence of CST or rubro-spinal tract regeneration. There was a modest improvement in locomotor behavior (BBB score of 2 to 7) which was likely mediated via the regeneration of the catecholaminergic projections (the paper is in review at Neuron). In terms of chronic spinal cord injury, we have recently shown impressive return of respiratory function 1.5 years after C2 hemisection lesion following a single injection of ch’ase at C4. The magnitude of functional recovery is far greater (by 4 fold) than that which occurs at acute stages. This is a fascinating discovery that we are still trying to understand. The result gives great hope to the SCI community. Importantly, our new chronic data along with that from the James Fawcett lab of a positive ch’ase effect on forepaw function in a chronic cord injury model has stimulated great interest from the International Spinal Research Trust (ISRT in England). I am very pleased and excited that serious talks about clinical trials are ongoing. Questions about which patients would best benefit from ch’ase administration; where, when and how much enzyme is to be delivered: ( the enzyme will likely be delivered well below the injury level rather that at the site of injury) and the role of rehab are all now being discussed

                Comment


                  OK, if axons were observed to clearly cross the lesion then this could be considered regeneration and since you did only label one side of the cortex that further helps confirm regeneration. However, the axons are not going very far and I don't see clear evidence of terminal arborizations. Also, I should point out that ch'ase helps to reduce the phenomenon of axonal dieback so without examining multiple intermediate time points one needs to be extra careful. The axons may not have retracted backwards in the first place. None-the-less, impressively long CST regeneration directly through or around a contusive lesion has never been shown after a single injection of ch'ase given in the vicinity of the lesion site. Going forward to humans ( and I surely hope we do) it is likely that ch'ase will be delivered via injection to the spinal cord gray matter well below the level of injury. The goal is to foster plasticity from any remaining but poorly functioning descending axons. The levels to be injected will need to be hotly discussed, but targeting the cervical or lumbar enlargements or lumbo-sacral region to restore some measure of hand, leg, or bladder/bowel/sexual function makes sense. Of course, a heavy dose of intensive rehab will be needed. I'd love to see a ch'ase component added to your patients.

                  Comment


                    Originally posted by jsilver View Post
                    OK, if axons were observed to clearly cross the lesion then this could be considered regeneration and since you did only label one side of the cortex that further helps confirm regeneration. However, the axons are not going very far and I don't see clear evidence of terminal arborizations. Also, I should point out that ch'ase helps to reduce the phenomenon of axonal dieback so without examining multiple intermediate time points one needs to be extra careful. The axons may not have retracted backwards in the first place. None-the-less, impressively long CST regeneration directly through or around a contusive lesion has never been shown after a single injection of ch'ase given in the vicinity of the lesion site. Going forward to humans ( and I surely hope we do) it is likely that ch'ase will be delivered via injection to the spinal cord gray matter well below the level of injury. The goal is to foster plasticity from any remaining but poorly functioning descending axons. The levels to be injected will need to be hotly discussed, but targeting the cervical or lumbar enlargements or lumbo-sacral region to restore some measure of hand, leg, or bladder/bowel/sexual function makes sense. Of course, a heavy dose of intensive rehab will be needed. I'd love to see a ch'ase component added to your patients.
                    Hello Dr Silver,

                    Do you think that incomplete injuries will be more likely to benefit from your new Ch'ase therapy. For instance people like me who have already a significant function back due to Brown Sequard Injury or other types of incomplete's that can walk with assistance of walkers and crutches and have significant function already but are still paralyzed to some degree.. From what I can understand this is where Ch'ase is proven to work best. Is that right?

                    Thank you for any response.
                    Regards,Bart.

                    Comment


                      Dr. Silver,

                      I have a couple of questions regarding Ch'ase.
                      It soulnds like this enzyme would not have much effect if there ar no remaining axons crossing the injury site. Why not perform a trial (once safety has been established in complete injuries) on patients with mild to moderate injuries? This would seem to be a potential quick win for many people like walking quads and paras (including me).
                      Also, about this new peptide you mentioned that can be delivered systemically, how do you know that there won't be any unnecessary (and possibly undesirable) "sprouting" in other areas of the spinal cord.

                      Thank you for your time and effort.

                      Comment


                        Originally posted by BSgimp View Post
                        Hello Dr Silver,

                        Do you think that incomplete injuries will be more likely to benefit from your new Ch'ase therapy. For instance people like me who have already a significant function back due to Brown Sequard Injury or other types of incomplete's that can walk with assistance of walkers and crutches and have significant function already but are still paralyzed to some degree.. From what I can understand this is where Ch'ase is proven to work best. Is that right?

                        Thank you for any response.
                        Regards,Bart.
                        Excellent question! I'm also a member of the Brown Sequard Injury club.
                        "I'm manic as hell-
                        But I'm goin' strong-
                        Left my meds on the sink again-
                        My head will be racing by lunchtime"

                        <----Scott Weiland---->

                        Comment


                          Dr.Silver ,
                          Hi , I have a question regarding chas' and contusion spinal cord injury . Did you do any experiments with CHAS' on chronic contusion spinal cord injury of rats in the last few years ? and if the answer is no what was the reason(s) not using the contusion version of rat's spinal cord injury in your lab when you were using CHAS' and graft experiment? are your current experiments with chas' is on chronic contusion spinal cord injury or you are using other kind of injury (comlete cut , etc. ) ? Do you think your CHAS' and graft experiment will be as effective on contusion injury as it is on complete cut, etc. ? thank you

                          Comment


                            Originally posted by BSgimp View Post
                            Hello Dr Silver,

                            Do you think that incomplete injuries will be more likely to benefit from your new Ch'ase therapy. For instance people like me who have already a significant function back due to Brown Sequard Injury or other types of incomplete's that can walk with assistance of walkers and crutches and have significant function already but are still paralyzed to some degree.. From what I can understand this is where Ch'ase is proven to work best. Is that right?

                            Thank you for any response.
                            Regards,Bart.

                            That is precisely correct. Those with some function and even minimal function below the level of injury and in addition, those who have worked hard via rehab to maintain muscle mass and regain as much as possible but have plateaued functionally have potentially the most to gain.

                            Comment


                              Originally posted by KofQ View Post
                              Dr. Silver,

                              I have a couple of questions regarding Ch'ase.
                              It soulnds like this enzyme would not have much effect if there ar no remaining axons crossing the injury site. Why not perform a trial (once safety has been established in complete injuries) on patients with mild to moderate injuries? This would seem to be a potential quick win for many people like walking quads and paras (including me).
                              Also, about this new peptide you mentioned that can be delivered systemically, how do you know that there won't be any unnecessary (and possibly undesirable) "sprouting" in other areas of the spinal cord.

                              Thank you for your time and effort.
                              Again, it is likely that those with some sparing below the injury level would be good initial candidates. However, we have the ability to build bridges across an injury site in our animal model with complete transection. So far our bridging techniques work at acute stages and we are now gearing up to do this at chronic stages. So far our peptide just makes our animals with severe contusive injuries urinate and walk much better and not worse. Whether there might be some cognitive changes (i.e.., memory loss or something like that ) will have to await further animal studies.

                              Comment


                                Originally posted by kz View Post
                                Dr.Silver ,
                                Hi , I have a question regarding chas' and contusion spinal cord injury . Did you do any experiments with CHAS' on chronic contusion spinal cord injury of rats in the last few years ? and if the answer is no what was the reason(s) not using the contusion version of rat's spinal cord injury in your lab when you were using CHAS' and graft experiment? are your current experiments with chas' is on chronic contusion spinal cord injury or you are using other kind of injury (comlete cut , etc. ) ? Do you think your CHAS' and graft experiment will be as effective on contusion injury as it is on complete cut, etc. ? thank you
                                So far we have only just begun to try to promote functional regeneration across a chronic contusive injury using grafting and ch'ase. We are not using just ch'ase alone to promote regeneration across a lesion for reasons that I had explained earlier in response to questions from Wise. We need to build a bridge and wake up axons that have been stuck in the scar for a long time. Ch'ase alone can't do this. My guess is that Liz Bradbury and others in England are already using ch'ase vectors caudal to the lesion to promote plasticity of spared fibers at chronic stages.

                                Comment

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