Long distance nerve regeneration via processed allografts in a caprine model

Information

  • Research Project
  • 7218849
  • ApplicationId
    7218849
  • Core Project Number
    R41HD053159
  • Full Project Number
    1R41HD053159-01A1
  • Serial Number
    53159
  • FOA Number
    PA-06-21
  • Sub Project Id
  • Project Start Date
    4/15/2007 - 17 years ago
  • Project End Date
    4/14/2009 - 15 years ago
  • Program Officer Name
    NITKIN, RALPH M
  • Budget Start Date
    4/15/2007 - 17 years ago
  • Budget End Date
    4/14/2009 - 15 years ago
  • Fiscal Year
    2007
  • Support Year
    1
  • Suffix
    A1
  • Award Notice Date
    4/11/2007 - 17 years ago
Organizations

Long distance nerve regeneration via processed allografts in a caprine model

[unreadable] DESCRIPTION (provided by applicant): Every year in the US, several million people suffer serious peripheral nerve injury. Injuries to the peripheral nervous system (PNS) are a major source of disability, impairing the ability to move muscles or to feel normal sensations. To treat these problems, more than one million procedures were performed in the US in 2002, totaling more than $10 billion in medical costs. Peripheral nerve injuries are under treated primarily because repair options are limited and ineffective. The clinical gold standard for repairing PNS injuries that cannot be repaired by direct coaptation is the use of nerve autograft, however, numerous clinical complications as well as a limited amount of expendable nerve segments, have necessitated a search for an alternative approach. Promising clinical results with nerve allografts has prompted research into various methods of preparing allografts to enable them to be more viable clinical options. Nerve allografts have been studied in small animal models (e.g. rat) for grafts ranging in length from 1 to 4cm. A large animal model would allow larger gaps to be created and incorporate long regeneration distances that would more closely model the challenge of human nerve grafting for severe traumatic or iatrogenic injuries. The overall aim of this Phase I project is to determine the feasibility of testing nerve allografts in a novel goat animal model which allows for functional and histomorphometric assays of axon regeneration efficacy though a large nerve gap and long regeneration distance to the muscle target tissue. Our proposed functional assay for motor axon regeneration is not available in other previously developed model systems. Feasibility of processing long multi-fasciculated nerves will be evaluated by applying a proprietary multistep allograft preparation method (already developed for rat tissue) to goat nerves which more closely mimic the size and complex structure of human nerves. Successful transfer of the graft preparation method will be determined by immunological analysis and histological analysis verifying (i) structural preservation of the graft and (ii) cellular removal and complete degradation of CSPG nerve growth inhibitors post-processing. Regeneration success in the goat will be determined by (i) evidence of regeneration into a muscle target to the level of muscle contraction using a novel functional assessment paradigm involving a tactile stimulus-activated polysynaptic spinal reflex and by (ii) a histomorphometric analysis of healthy regenerated axons in the distal nerve segment of the recipient. Every year in the US, several million people suffer serious peripheral nerve injury. Injuries to the peripheral nervous system (PNS) are a major source of disability, impairing the ability to move muscles or to feel normal sensations. [The product that would result from a successful project would be an unmatched treatment option for these patients and would be the only commercially available long graft alternative to nerve autograft.] [unreadable] [unreadable] [unreadable]

IC Name
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT
  • Activity
    R41
  • Administering IC
    HD
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    102737
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    865
  • Ed Inst. Type
  • Funding ICs
    NICHD:102737\
  • Funding Mechanism
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    AXOGEN, INC.
  • Organization Department
  • Organization DUNS
    113424464
  • Organization City
    GAINESVILLE
  • Organization State
    FL
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    326357787
  • Organization District
    UNITED STATES