A novel therapy to promote axonal fusion in human digital nerves

Bamba, Ravinder; Waitayawinyu, Thanapong; Nookala, Ratnam; Riley, David C.; Boyer, Richard B.; Sexton, Kevin W.; Boonyasirikool, Chinnakart; Niempoog, Sunyarn; Kelm, Nathaniel D.; Does, Mark D.; Dortch, Richard D.; Shack, R. Bruce; Thayer, Wesley P.

doi:10.1097/ta.0000000000001203

Cited by 40 publications

(31 citation statements)

References 23 publications

(29 reference statements)

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“…PEG-fusion has obvious potential to greatly benefit patients with such injuries by dramatically increasing the speed and magnitude of functional recovery. To date, limited clinical case studies (n=5) strongly suggest that PEG-fusion indeed produces very favorable outcomes for single transection injuries (Bamba et al, 2016b; Trevino, personal communications). Use of PEG-fusion in conjunction with neurorraphy for single-cut and ablation injuries has the potential to greatly contribute to clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats

Mikesh

Ghergherehchi

Rahesh

et al. 2018

J of Neuroscience Research

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Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats

Mikesh

Ghergherehchi

Rahesh

et al. 2018

J of Neuroscience Research

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“…As per their original and erratum text, Salomone et al 1 use an incorrect 500 mM solution of 200 Da PEG, not a 50% w/w or 500 m solution (abbreviated mm, not mM) of 2000 Da PEG as previously published in 2012 2 or a 500 mm solution of 3350 Da PEG as published in subsequent papers. [3][4][5][6][7][8][9][10][11][12] It has long been known 13 that PEG solutions of less than 1000 Da do not produce PEG-fusion by joining (annealing) open, apposed axonal ends, but rather almostcertainly seal off those severed axonal ends thereby preventing them from fusing (annealing, joining). [6][7][8][9][10][11][12][13][14][15] It is beneficial that a hypotonic, Ca 2+ -free solution be used to expel vesicles before PEG is applied.…”

Section: Inappropriate Methods For Evaluation Of Peg-fusion a Methodsmentioning

confidence: 99%

“…Resection/trimming in the presence of hypotonic solutions would "re-open" axonal ends. 2,6-16 Bamba et al [3][4][5] also note that nerves were resected immediately prior to repair following a delay from injury in rats or in case studies.…”

Section: Inappropriate Methods For Evaluation Of Peg-fusion a Methodsmentioning

confidence: 99%

Salomone et al did not induce PEG‐fusion repair of severed rat facial nerves

et al. 2019

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“…This repair method was recently used in humans for the first time, in digit re-implantation, with positive results, but requires further clinical study to determine its long-term efficacy and widespread application. 54 …”

Section: Polyethylene Glycol Fusionmentioning

confidence: 99%

Advances in peripheral nerve regeneration as it relates to VCA

Suchyta

Sabbagh

Morsy

et al. 2016

Vascularized Composite Allotransplantation

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Vascularized composite allotransplant (VCA) offers functional, social, and quality of life improvements for patients who have exhausted traditional reconstructive options. Unlike solid organ transplant, VCA success is not only based upon the quality of perfusion and level of immunosuppression, but also on the success of nerve regeneration within the transplanted part. This paper will summarize the present state of peripheral nerve regeneration in the context of VCA and will explore the latest research advances that will affect the future of the field. These advances offer promising future strategies to improve patient outcomes in VCA.

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A novel therapy to promote axonal fusion in human digital nerves

Abstract: Therapeutic study, level IV.

Cited by 40 publications

References 23 publications

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats

Salomone et al did not induce PEG‐fusion repair of severed rat facial nerves

Advances in peripheral nerve regeneration as it relates to VCA

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