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  1. #1
    Senior Member lunasicc42's Avatar
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    question for wise

    Quote Originally Posted by Wise Young
    Quote Originally Posted by lunasicc42
    Considering the results are so old. I mean when I go on Pubmed or something similar, they have results that show hope but it's like a good experiment but it doesn't come to fruition

    http://www.ncbi.nlm.nih.gov/pubmed/11352090

    I mean I see that it says that it promotes recovery. Why aren't such things here when they have been discovered so long ago?
    You should ask this question in the Cure Forum so that I can answer it there. Wise.
    Question
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  2. #2
    Quote Originally Posted by lunasicc42 View Post
    Question
    There are two issues raised by your question. The first is whether this article has the evidence and the basis for calling this therapy a promising therapy for spinal cord injury. The second is, if it is indeed promising, why did it not go forward to clinical trial.

    Neurogel was a biomaterial that was claimed to support axonal growth. At the time it came out, there was several competing biomaterials that other scientists were using. It belonged to a class of biomaterials called hydrogels. A total of 5 papers were published:
    1. Woerly S, Awosika O, Zhao P, Agbo C, Gomez-Pinilla F, de Vellis J and Espinosa-Jeffrey A (2005). Expression of heat shock protein (HSP)-25 and HSP-32 in the rat spinal cord reconstructed with Neurogel. Neurochem Res 30: 721-35. Organogel Canada Ltee, 1400 Parc Technologique Blvd, GIP 4R7, Quebec, Quebec, Canada. We recently showed a successful reconstruction of the cat spinal cord using NeuroGel a polymer hydrogel bridge between the two spinal stumps. The polymer graft supports axonal elongation, myelination and angiogenesis up to 21 months, Wallerian degeneration was diminished and gliotic scarring was prevented. In the present study, we report the expression patterns of two stress proteins, (HSPs) HSP-25 and HSP-32 after spinal cord hemisection with and without reparative surgery with NeuroGel. Double immunofluorescence using cell specific markers for neurons, astrocytes and oligodendrocytes (OL), in combination with antibodies for HSP-25 and 32 showed that mainly neurons express both proteins. Both HSPs displayed different temporal expression patterns in the reconstructed spinal cords with a concomitant reduction of secondary damage. In conclusion, Neurogel reconstruction of the spine during the acute phase considerably reduces secondary damage resulting in a rapid and stable regenerative response.
    2. Woerly S, Doan VD, Sosa N, de Vellis J and Espinosa-Jeffrey A (2004). Prevention of gliotic scar formation by NeuroGel allows partial endogenous repair of transected cat spinal cord. J Neurosci Res 75: 262-72. Organogel Canada Ltee, Sainte-Foy, Quebec, Canada. Spinal cords of adult cats were transected and subsequently reconnected with the biocompatible porous poly (N-[2-hydroxypropyl] methacrylamide) hydrogel, NeuroGel. Tissue repair was examined at various time points from 6-21 months post reconstructive surgery. We examined two typical phenomena, astrogliosis and scar formation, in spines reconstructed with the gel and compared them to those from transected non-reconstructed spines. Confocal examination with double immunostaining for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed that the interface formed between the hydrogel and the spine stumps did prevent scar formation and only a moderate gliosis was observed. The gel implant provided an adequate environment for growth of myelinated fibers and we saw angiogenesis within the gel. Electron microscopy showed that regenerating axons were myelinated by Schwann cells rather than oligodendrocytes. Moreover, the presence of the gel implant lead to a considerable reduction in damage to distal caudal portions of the spine as assessed by the presence of more intact myelinated fibers and a reduction of myelin degradation. Neurologic assessments of hindlimb movement at various times confirmed that spinal cord reconstruction was not only structural but also functional. We conclude that NeuroGel lead to functional recovery by providing a favorable substrate for regeneration of transected spinal cord, reducing glial scar formation and allowing angiogenesis.
    3. Woerly S, Doan VD, Evans-Martin F, Paramore CG and Peduzzi JD (2001). Spinal cord reconstruction using NeuroGel implants and functional recovery after chronic injury. J Neurosci Res 66: 1187-97. Organogel Canada Ltee, 1400 Parc Technologique Blvd., Quebec City, Quebec G1P 4R7, Canada. woerlyst@organogel.com. There is currently a lack of effective ways to achieve functional tissue repair of the chronically injured spinal cord. We investigated the potential of using NeuroGel, a biocompatible polymer hydrogel, to induce a reconstruction of the rat spinal cord after chronic compression-produced injury. NeuroGel was inserted 3 months after a severe injury into the post-traumatic lesion cavity. Rats were placed in an enriched environment and the functional deficits were measured using the BBB rating scale. A significant improvement in the mean BBB scores was observed. Rats without enriched environment and severely injured rats with an enriched environment alone showed no improvement; however, 7 months after reconstructive surgery using NeuroGel, a reparative neural tissue had formed within the polymer gel that included myelinated axons and dendro-dendritic contacts. NeuroGel implantation into a chronic spinal cord injury therefore resulted in tissue reconstruction and functional improvement, suggesting that such an approach may have therapeutic value in the repair of focal lesions in humans.
    4. Woerly S, Pinet E, de Robertis L, Van Diep D and Bousmina M (2001). Spinal cord repair with PHPMA hydrogel containing RGD peptides (NeuroGel). Biomaterials 22: 1095-111. Organogel Canada Ltee, Quebec, QC. woerlyst@organogel.com. A biocompatible hydrogel of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) which includes the cell-adhesive region of fibronectin Arg-Gly-Asp was synthesized and its structure, rheological and dielectric properties were characterized. The ability of a PHPMA-RGD hydrogel to promote tissue regeneration and support axonal outgrowth in the injured adult and developing rat spinal cord was evaluated. The structure of the PHPMA-RGD hydrogel displayed an interconnected porous structure, with viscoelastic properties similar to those of the neural tissue, and conductivity properties due to a peptide group. The polymer hydrogel provided a structural, three-dimensional continuity across the defect, facilitating the migration and reorganization of local wound-repair cells, as well as tissue development within the lesion. Angiogenesis and axonal growth also occurred within the microstructure of the tissue network, and supraspinal axons migrated into the reconstructed cord segment. In addition, the hydrogel induced a reduction of necrosis and cavitation in the adjacent white and gray matter. These polymer hydrogel matrices therefore display the potential to repair tissue defects in the central nervous system by enhancing the development of a tissue equivalent as well as axonal growth across the reconstructed lesion.
    5. Woerly S, Doan VD, Sosa N, de Vellis J and Espinosa A (2001). Reconstruction of the transected cat spinal cord following NeuroGel implantation: axonal tracing, immunohistochemical and ultrastructural studies. Int J Dev Neurosci 19: 63-83. Organogel Canada Ltee, 1400 Parc Technologique Blvd, G1P 4R7, Quebec, Canada. woerlyst@organogel.com. This study examined the ability of NeuroGel, a biocompatible porous poly [N-(2-hydroxypropyl) methacrylamide] hydrogel, to establish a permissive environment across a 3 mm gap in the cat spinal cord in order to promote tissue reconstitution and axonal regeneration across the lesion. Animals with NeuroGel implants were compared to transection-only controls and observed for 21 months. The hydrogel formed a stable bridge between the cord segments. Six months after reconstructive surgery, it was densely infiltrated by a reparative tissue composed of glial cells, capillary vessels and axonal fibres. Axonal labelling and double immunostaining for neurofilaments and myelin basic protein, showed that descending supraspinal axons of the ventral funiculus and afferent fibres of the dorsal column regenerated across the reconstructed lesion. Fifteen months after reconstructive surgery, axons had grown, at least, 12 mm into the distal cord tissue, and in the rostral cord there was labelling of neurons of the intermediate gray matter. Electron microscopy showed that after 9 months, most of the regenerating axons were myelinated, principally by Schwann cells. Newly formed neurons presumably from precursor cells of the ependyma and/or migrating neurons were observed within the reparative tissue after 21 months. Results indicate that functional deficit, as assessed by treadmill training, and morphological changes following double transection of the spinal cord can be modified by the implantation of NeuroGel. This technology offers the potential to promote the formation of a neural tissue equivalent via a reparative neohistogenesis process, that facilitates and supports regenerative growth of axons.
    6. Woerly S (2000). Restorative surgery of the central nervous system by means of tissue engineering using NeuroGel implants. Neurosurg Rev 23: 59-77; discussion 78-9. Organogel Canada Ltee, Quebec, Quebec. A novel approach aimed at restoring tissue structure and function and enhancing axonal recovery in damaged parts of the central nervous system is described. In contrast to contemporary neurotransplantation technologies which focus on tissue reconstruction of neural parenchyma by cell replacement, this approach is based on repair by tissue engineering. The technique involves the implantation of a 3-dimensional polymer hydrogel into the site of injury. The physical properties of the hydrogel induce the organisation of migrating wound-healing cells and regenerating axons within its 3-dimensional structure. Two complementary approaches are described and illustrated using results obtained in vivo and in vitro: (1) implantation into the brain and spinal cord of the polymer hydrogel NeuroGel, which has a defined macromolecular structure that enhances tissue-building capabilities, and the implantation of advanced hydrogel derivatives carrying biologically active molecules to promote selective cell interactions, and (2) biohybrid hydrogels that contain entrapped developing neural tissue cells, embryonic carcinoma-derived neurons, or genetically modified cells which secrete neurotrophic factors. These techniques create bioartificial tissues with neural tissue specificity. The potential of this biomaterial-based approach to neural tissue engineering for restorative neurosurgery is discussed.


    If the material is so promising, why didn't other scientists pick it up? For a long time, the material was not available for study. The company that made it went under. It recently became available through the efforts of a patient group that believed in its efficacy. One laboratory has started using it and found that it is beneficial in animal models and is proposing to take it into clinical trial.

    Clinical application may be difficult. The vast majority of spinal cord injuries do not involve transection. Rather the spinal cord is contused. How do you apply a biomaterial to the spinal cord. The studies that were carried out did not assess it in contused spinal cords. Does one do what Carlos Lima's group does, by cutting a piece of spinal cord out? That is difficult to justify. The other approach may be to remove the necrotic tissue in the middle of the spinal cord in subacute spinal cord injury.

    So, a combination of factors held back neurogel. The first and most proximate cause is the failure of the company that was developing neurogel to raise money for its development. The second was the failure to interest other scientists in the use of the biomaterial at the time. The third is how to apply the material to the spinal cord. Finally, while there is a resurgence of interest in the material recently, it still needs a champion and somebody who can raise the money to take this to clinical trial.

    Wise.

  3. #3
    Senior Member lunasicc42's Avatar
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    didn't you say in the earlier Neurogel thread that you would cosider using Neurogel in an addition to your proposed Treatment? How does that look?
    "That's not smog! It's SMUG!! " - randy marsh, southpark

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  4. #4
    Quote Originally Posted by lunasicc42 View Post
    didn't you say in the earlier Neurogel thread that you would cosider using Neurogel in an addition to your proposed Treatment? How does that look?
    Please, things don't go that fast. We have to get funding, permission (permission to do animal studies must be applied for), and then the neurogel itself. We already have a lot of experiments already scheduled between now and July. We probably won't start those experiments until this summer.

    Wise.

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    Dr. Young,

    Mr. Rondio has offered to provide you with lots of Neurogel. I am sure Prs. Sykova, Gorio and Decherchi would be glad to work with you – this would be in keeping with the spirits of the IANR, of which Pr. Sykova and yourself are members. Pr. Sykova needs a fairly small amount of money to complete her pre-clinical work - around $300,000 I believe. Can you suggest a way we can raise funding, or team to try to arrange funding to help you jointly conduct an experiment – say, this summer - that would validate the product. Can you be our champion and help us launch multi-center clinical trials ? If there is any possibility at all that this therapy might work, isn’t it worth a try ?
    gretchen 1

  6. #6
    Quote Originally Posted by gretchen View Post
    Dr. Young,

    Mr. Rondio has offered to provide you with lots of Neurogel. I am sure Prs. Sykova, Gorio and Decherchi would be glad to work with you – this would be in keeping with the spirits of the IANR, of which Pr. Sykova and yourself are members. Pr. Sykova needs a fairly small amount of money to complete her pre-clinical work - around $300,000 I believe. Can you suggest a way we can raise funding, or team to try to arrange funding to help you jointly conduct an experiment – say, this summer - that would validate the product. Can you be our champion and help us launch multi-center clinical trials ? If there is any possibility at all that this therapy might work, isn’t it worth a try ?
    Gretchen,

    Thanks. As soon as I get a chance, I will try to write a protocol for our experiments. I am hoping to assess the effects of another promising biomaterial (Self-Assembling Peptide) this coming summer. We have applied for a grant to do this and I am hopeful that we will get the funds before the summer. I was thinking that we can add an experimental group in that series, using neurogel.

    If the treatment looks good, this is something that we can move rapidly into clinical trial both in China and the United States. Unfortunately, I won't have a chance to talk to Eva Sykova. I understand that she will be at the IANR meeting in Beijing in April but unfortunately I am committed to go to a meeting in Taiwan at exactly the same time. Alfredo Gorio and I are long time friends, dating back 30 or more years.

    Regarding fundraising, I will coming to Vienna on March 19-23 and hope to talk to Paolo Cipolla and Corinne Jeanmaire about spinal cord injury research fundraising and particularly for European spinal cord injury clinical trials. It is, as you know, very tough. Almost all the foundations have contracted and fundraising is about as tough as I have seen it in over 30 years. It is a very tough time for many spinal cord injury laboratories. Of course, I will recommend that your group be included in any effort.

    Wise.

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