Page 3 of 4 FirstFirst 1234 LastLast
Results 21 to 30 of 31

Thread: ? for jerry silver

  1. #21
    Also is there a place where we can follow the progress and development of the ch'ase treatment?

    And honestly sounds pretty promising. So if Im understanding this right, ch'ase has the potential to restore lower function for a T level contusion injury?

  2. #22
    I would suggest 2 things that you can do to follow the most current research around the globe with the use of ch'ase. You can go to the Society for Neuroscience website to read the current abstracts of work that will be presented in New Orleans in October. Go to the website below and the Advanced Search, type in the word "chondroitinase" on the line entitled "Abstract Body" then click the search button at the bottom. 23 abstracts will appear.

    http://www.abstractsonline.com/plan/AdvancedSearch.aspx


    The second thing you can do is to follow what may be presented at the U2FP website or what might be posted here at CC following the forthcoming W2W meeting.

    And yes the enzyme could potentially help those with lower level injuries especially if the injury is incomplete.

  3. #23
    jsilver, some elaboration to this "potentially", please.

  4. #24
    Quote Originally Posted by kivi66 View Post
    jsilver, some elaboration to this "potentially", please.
    There is new hope for the use of viral delivery of ch'ase as a way to treat a much broader area of the cord and for more lengthy time periods. Because contusive lesions are so large simple injection of the enzyme after such injuries has not been very successful. Things are changing now and here is an abstract from the Bradbury lab to explain this new strategy. We are also using this viral delivery strategy in our lab as well as our new peptide to produce long term, widespread effects

    Program#/Poster#: 270.07/EE19
    Presentation Title: Gene delivery of chondroitinase ABC promotes functional repair following spinal cord injury
    Location: Hall F-J
    Presentation time: Sunday, Oct 14, 2012, 3:00 PM - 4:00 PM
    Authors: *N. D. JAMES1, K. BARTUS1, J. SHEA1, K. BOSCH1, J. H. ROGERS2, S. B. MCMAHON1, B. L. SCHEIDER3, E. M. MUIR2, E. J. BRADBURY1;
    1King's Col. London, London, United Kingdom; 2Univ. of Cambridge, Cambridge, United Kingdom; 3Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Abstract: Spinal cord extracellular matrix is densely packed with growth inhibitory chondroitin sulphate proteoglycans (CSPGs), which become more abundant after injury. Thus, matrix modification has become a leading experimental strategy for promoting repair following spinal cord injury. Despite the beneficial effects that have been achieved by digesting CSPGs with the bacterial enzyme chondroitinase ABC (ChABC), the potential for achieving long term efficacy in traumatic injuries that mimic a human spinal cord injury has not yet been realised. Gene therapy offers a route to achieving stable continuous delivery of ChABC and therefore, here we deliver genetically modified ChABC via a lentiviral vector (LV-ChABC) to the adult rat spinal cord and assess the efficacy of chronic gene delivery using a spinal contusion injury model. Contusion injury represents the most common form of spinal cord injury in humans and, therefore, provides a clinically relevant tool for assessing the efficacy of potential therapeutic interventions. Adult rats received a moderate severity thoracic (T10) contusion injury and LV-ChABC or a control LV-GFP was immediately injected rostral and caudal to the injury site. We demonstrate prolonged and widespread CSPG degradation with LV-ChABC and, using both behavioural and electrophysiological outcome measures, we show improved function in animals treated with LV-ChABC. We saw a dramatic increase in spinal conduction through the injury site as well as a significant improvement in performance on the horizontal ladder test. In addition we will determine if the early functional improvements observed using the horizontal ladder test correlate with changes in spinal conduction at early time points. In order to enhance the potential clinical applications of this study we are now assessing the effects of LV-ChABC in a moderate severity cervical (C5) contusion injury. Approximately 50% of all human spinal cord injuries occur at the cervical level making this injury model of particular clinical relevance as well as allowing us to assess a number of additional functional outcomes such as forelimb grip-strength, sensory and motor function during sticky-tape removal, and proprioception using the inclined plane. Thus, we demonstrate the potential advantages of gene delivery of ChABC for achieving sustained and widespread CSPG degradation and that this is associated with functional improvements following contusion injury.

  5. #25
    Quote Originally Posted by kivi66 View Post
    jsilver, some elaboration to this "potentially", please.
    I might as well post our peptide story as well. All SFN abstracts are now public knowledge.

    Program#/Poster#: 252.07/M6
    Presentation Title: Peptide inhibitors of LAR family phosphatases release CSPG mediated entrapment of axons and promote robust behavioral recovery following contusive spinal cord injury.
    Location: Hall F-J
    Presentation time: Sunday, Oct 14, 2012, 3:00 PM - 4:00 PM
    Authors: *B. T. LANG1, J. M. CREGG1, M. A. DEPAUL1, A. R. FILOUS1, T. A. EVANS1, Y. L. WENG1, A. Y. HUANG2, S. LI3, J. SILVER1;
    1Dept. of Neurosciences, 2Dept. of Pediatrics, Case Western Reserve Univ., Cleveland, OH; 3Neurol. and Neurosci. Grad. Program, Univ. of Texas Southwestern Med. Ctr., Dallas, TX
    Abstract: Regeneration following spinal cord injury is curtailed by several processes, with the inhibitory chondroitin-sulfate proteoglycan (CSPG) rich glial scar being the primary impediment. Recent reports have identified the pro-synaptic proteins, Protein Tyrosine Phosphatase-Sigma (PTPσ) and Leukocyte common Antigen-Related (LAR) as the first CSPG receptors, although it is currently unknown how these receptors function to prevent axonal regeneration. Using an in vitro assay of the glial scar and time-lapse microscopy, we show that long-term exposure to gradients of CSPGs causes growth cones to stabilize and over-adhere within the CSPG substrate. Immunohistochemical analyses showed that PTPσ and LAR become highly concentrated in the terminally stabilized growth cones. A small membrane penetrating peptide inhibitor of the intracellular domain of LAR or a similar novel peptide inhibitor of PTPσ added to the cultures prevented the stabilization and over-adhesion of growth cones and allowed motility even after the longest exposure to CSPG. Furthermore, peptide treatment could reactivate growth cones into a highly motile state even after stabilization. One day following spinal cord injuries inflicted via an Infinite Horizon device, we administered long-term daily subcutaneous injections of each peptide, a combination of both or a vehicle control. Inactivation of RPTPσ, but not LAR, following severe contusive spinal cord injury allowed for remarkable recovery of hindlimb function, locomotor activity, and bladder control. Our results suggest for the first time that CSPGs in the lesion environment block regenerative growth by creating an abnormally high adhesive interaction between the substrate and the dystrophic axon. Furthermore, we show that LAR and PTPσ can be modulated and inactivated to prevent the over-adhesion and stabilization of axons following spinal cord injury. Most importantly, inactivation of PTPσ with a novel, easily injectable, small peptide inhibitor allowed unprecedented levels of functional recovery following spinal cord injury, presenting a potential new avenue of treatment for paralysis.

  6. #26
    Dr. Silver,
    Hi, thanks for your post. sorry i am not sure if i understand it correctly, is the above abstract from your lab for acute, subacute , or chronic spinal cord injury . Thanks

  7. #27
    sorry , i see it now, it says " one day following spinal cord injuries......" , so it seems it is acute spinal cord injury .do you think you will get the same results in chronic spinal cord injury?

  8. #28
    Quote Originally Posted by kz View Post
    sorry , i see it now, it says " one day following spinal cord injuries......" , so it seems it is acute spinal cord injury .do you think you will get the same results in chronic spinal cord injury?
    These are the experiments that we are doing now.

  9. #29
    Quote Originally Posted by kz View Post
    sorry , i see it now, it says " one day following spinal cord injuries......" , so it seems it is acute spinal cord injury .do you think you will get the same results in chronic spinal cord injury?
    "Furthermore, peptide treatment could reactivate growth cones into a highly motile state even after stabilization."
    jsilver, can it be a positive answer to kz's question?
    Thanks a lot for your work. You know, it's possible that the word "researcher" could cease to be for me a curse.

  10. #30
    This is a quote from another post by Jerry Silver with regard to whether the peptide is being tested for chronic sci.

    "We have now constructed the peptide which can be simply injected under the skin or via other potential easy routes of administration. It is designed to penetrate into the CNS even if given systemically. We are doing both acute and, of course, chronic experiments."

Similar Threads

  1. Jerry Silver talks to me
    By Christopher Paddon in forum Cure
    Replies: 118
    Last Post: 06-10-2012, 09:53 AM
  2. open question to wise and jerry silver
    By lunasicc42 in forum Cure
    Replies: 12
    Last Post: 12-16-2011, 02:26 PM
  3. Replies: 53
    Last Post: 11-23-2011, 08:24 AM
  4. jerry Silver wins Javits Award
    By Max in forum Funding, Legislation, & Advocacy
    Replies: 3
    Last Post: 12-10-2004, 09:51 PM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •