Translating Novel Peripheral Nerve Allograft Technologies Toward Clinical Use

PROJECT SUMMARY/ABSTRACT
Peripheral nerve injuries (PNIs) that result in nerve gap (segmental-loss, ablation) defects are the most
common and costly cause of temporary and permanent nervous system dysfunction. The current best clinical
practice to repair ablation PNIs is to suture to host nerves bridging devices such as autografts, acellular nerve
allografts or synthetic conduits. Outcomes are poor because the return of any sensation or behavioral recovery
depends upon slow and imprecise axonal outgrowths, often taking months to years to re-innervate targets. Viable
peripheral nerve allografts (PNAs) are rarely used experimentally or clinically due to the risks of
immunosuppressive therapy and graft rejection.
To greatly improve current treatments for segmental-loss PNIs, our team will translate our synergistic
technologies of localized immunosuppression and polyethylene -induced axon fusion (PEG-fusion) of viable
PNAs. PEG-fusion of PNAs rapidly (within minutes) restores cytoplasmic/electrical continuity and prevents
Wallerian Degeneration to 40-60% of axons, immediately re-innervates denervated tissues and reliably promotes
a highly accelerated return of voluntary behaviors within weeks. PEG-fused chimeric axonal segments within
PNAs are not rejected by the host even without immune suppression (ISN) and tissue matching. Localized ISN
further reduces the immune response.
Translation of PEG-fused PNAs with localized ISN technologies would produce a paradigm shift from
current clinical practice of waiting days to months to repair ablation PNIs with autografts, acellular nerve allografts
or conduits, where the patient outcome is solely dependent upon axon regeneration. In contrast, repairing
ablation PNIs by PEG-fusion/localized ISN of donor allografts applied within three days of injury would generate
significantly improved functional outcomes (weeks instead of months/years) produced by PEG- fusion axons and
robust regeneration of non-fused axons through the viable PNA enhanced by localized ISN.
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Grant Number: 5R01NS128086-03
NIH Institute/Center: NIH
Principal Investigator: GEORGE BITTNER