We proved that the natural activity of the immune system can protect nerve cells against degeneration and also help in recovery following CNS (Central nerves system) trauma
Technology
Proneuron Biotechnologies is enrolling patients suffering from complete spinal cord injuries to participate in a Phase II multi-center clinical study. Patients within 14 days of injury will be implanted with ProCord. Proneuron Biotechnologies, a Delaware company, is in advanced stages of clinical development in a number of attractive neurological markets. Proneuron is the first company to harness the power of the body's own immune system for the treatment of debilitating central nervous system (CNS) disorders. The concept of helping the body to "cure" itself, offers hope to the millions of victims of nervous system-related disorders. Proneuron Biotechnologies is developing therapies for neurological disorders, including spinal cord injury (SCI), other central nervous system trauma and back injuries. Our products are based on proprietary technology for modulating the interaction between the nervous system and the immune system. Proneuron is enrolling a total of 61 patients suffering from complete spinal cord injuries in a Phase II multi-center clinical study. Patients will be implanted with ProCord. Study sites must be informed of a candidate patient within a few days of the spinal cord injury to allow time to complete the necessary tests and procedures within 14 days of injury.
We proved that the natural activity of the immune system can protect nerve cells against degeneration and also help in recovery following CNS (Central nerves system) trauma
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A large number of scientific articles concerning Proneuron's technology have been published by prestigious journals. Following is a list of the important articles (you may click on an item to access the abstract from the PubMed site):

Following are abstracts of some of the articles. For more information please contact us at information@proneuron.com

  • Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats
    O. Rapalino, O. Lazarov-Spiegler, E. Agranov, G.J. Velan, E. Yoles, M. Fraidakis, A. Solomon, R. Gepstein, A. Katz, M. Belkin, M. Hadani and M. Schwartz

    Nature Medicine, 4:814-821 (1998).

    Abstract
    Postinjury recovery in most tissues requires an effective dialog with macrophages; however in the mammalian central nervous system this dialog may be restricted (possibly due to its immune-privileged status), which probably contributes to its regeneration failure. We circumvented this by implanting pre-exposed ex vivo to peripheral nerve segments, into transected rat spinal cord. This stimulated tissue repair and partial recovery of motor function, manifested behaviorally by movement of hind limbs, plantar placement of the paws and weight support, and electrophysiologically by cortically-evoked hind-limb muscle response. We substantiated these findings immunohistochemically by demonstrating continuity of labeled nerve fibers across the transected site and by tracing descending fibers distally to it by anterograde labeling. In recovered rats, retransection of the cord above the primary transection site led to loss of recovery, indicating the involvement of long descending spinal tracts. Injection of macrophages into the site of injury is relatively non-invasive and, as the cells are autologous, it may be developed into a clinical therapy.

     

  • Restricted inflammatory reaction in the CNS: a key impediment to axonal regeneration?
    O. Lazarov-Spiegler, O. Rapalino, G. Agranov and M. Schwartz

    Molec. Med. Today, 4:337-342 (1998).

    Abstract
    Axons in the central nervous system (CNS) of adult mammals do not regenerate after injury. Mammalian CNS differs in this respect from other mammalian tissues, including the peripheral nervous system (PNS) and from the CNS of lower vertebrates. In most parts of the body, including the nervous system, injury triggers an inflammatory reaction involving macrophages. This reaction is needed for tissue healing; when it is delayed or insufficient, healing is incomplete. The CNS, although needing an efficient inflammatory reaction resembling that in the periphery for tissue healing, appears to have lost the ability to supply it. We suggest that restricted CNS recruitment and activation of macrophages are linked to regeneration failure and might reflect the immune privilege that characterizes the mammalian CNS. As macrophages play a critical role in tissue restoration, and because their recruitment and activation are among the most upstream of the events leading to tissue healing, overcoming the deficiencies in these steps might trigger a self-repair process leading to recovery after CNS injury.

     

  • Peripheral nerve stimulated macrophages are beneficial for optic nerve regrowth
    O. Lazarov-Spiegler, A.S. Solomon and M. Schwartz

    Glia, 24:329-337 (1998).

    Abstract
    We have previously demonstrated that the failure of the mammalian central nervous system (CNS) to regenerate following axonal injury is related to its immunosuppressive nature, which restricts the ability of both recruited blood-borne monocytes and CNS-resident microglia to support a process of repair. In this study we show that transected optic nerve transplanted with macrophages stimulated by spontaneously regenerative nerve tissue, e.g., segments of peripheral nerve (sciatic nerve), exhibit axonal regrowth at least as far as the optic chiasma. Axonal regrowth was confirmed by double retrograde labeling of the injured optic axons, visualized in their cell bodies. Transplanted macrophages exposed to segments of CNS (optic) nerve were significantly less effective in inducing regrowth. Immunocytochemical analysis showed that the induced regrowth was correlated with a wide distribution of macrophages within the transplanted-transected nerves. Concomitantly, it was correlated with enhancement of clearance of myelin, known to be inhibitory for regrowth and poorly eliminated after injury in the CNS. These results emphasize that healing of the injured mammalian CNS, like healing of any other injured tissue, requires the partnership of the immune system, which is normally restricted, but that the restriction can be circumvented by transplantation of peripheral nerve-stimulated macrophages.

     

  • Potential Repair of Rat Spinal Cord Injuries Using Stimulated Homologous Macrophages
    Michal Schwartz, Ph.D.; Orly Lazarov-Spiegler, M.Sc.; Otto Rapalino, M.D.; Ivgenia Agranov, M.D.; Gad Velan, M.D.; Moshe Hadani, M.D.

    Neurosurgery, 44:1041-1046, (1999).

    Abstract
    The failure of the adult mammalian central nervous system (CNS) to regenerate after injury has long been viewed as a unique phenomenon resulting from the specific nature of this system. The finding that some CNS axons could be induced to regrow if provided with a permissive environment suggested that this failure is a result, at least in part, of the nature of the post injury neuronal environment. It was further shown that the involvement of inflammatory cells, particularly macrophages, in postinjury processes in the CNS is limited. We have suggested that, to achieve recovery after injury, the adult mammalian CNS may require the assistance of the same postinjury factors as those involved in the recovery of spontaneously regenerating systems but that its accessibility to such assistance is restricted. Accordingly, we proposed that it might be possible to circumvent the restriction, allowing regeneration to occur. We showed that the implantation of autologous macrophages, which had been prestimulated by exposure to a regenerative (sciatic) nerve, into completely transected spinal cords of adult rats led to partial motor recovery. This treatment intervenes in the postinjury process by simulating in the axotomized CNS the events that occur naturally in spontaneously regenerating systems.


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