Bridging the gap: Spinal cord fusion as a treatment of chronic spinal cord injury

Abstract

Despite decades of animal experimentation, human translation with cell grafts, conduits, and other strategies has failed to cure patients with chronic spinal cord injury (SCI). Recent data show that motor deficits due to spinal cord transection in animal models can be reversed by local application of fusogens, such as Polyethylene glycol (PEG). Results proved superior at short term over all other treatments deployed in animal studies, opening the way to human trials. In particular, removal of the injured spinal cord segment followed by PEG fusion of the two ends along with vertebral osteotomy to shorten the spine holds the promise for a cure in many cases.

BAPTA, a calcium chelator, neuroprotects injured neurons in vitro and promotes motor recovery after spinal cord transection in vivo

“…LIA has been theorized as a feasible strategy in the context of human SCI and is currently being tested in an ongoing clinical trial, with initial promising results 30 . In particular, it has been proposed that the only feasible therapeutic approach to chronic SCI is removal of the most heavily damaged portion of the cord and replacement with healthy tissue 31 . PEG primarily acts by reducing apoptosis of gray matter cells allowing them to resprout and reestablish communication across the treatment interface between the primary cord and the grafted tissue.…”

“…30 In particular, it has been proposed that the only feasible therapeutic approach to chronic SCI is removal of the most heavily damaged portion of the cord and replacement with healthy tissue. 31 PEG primarily acts by reducing apoptosis of gray matter cells allowing them to resprout and reestablish communication across the treatment interface between the primary cord and the grafted tissue. In such a scenario, other chemicals with a similar profile to PEG can be explored, for possible combination treatment.…”

Transplantation of a vascularized pedicle of hemisected spinal cord to establish spinal cord continuity after removal of a segment of the thoracic spinal cord: A proof‐of‐principle study in dogs

“…This finding lends support to another possible approach espoused originally by Freeman et al in the 1960s, involving complete extirpation of the SCI epicenter, spinal shortening, and apposition of the freshly sectioned cord ends. 7 , 54 Using the hypothetical approach of Freeman, however, requires the need to remove one vertebra en bloc, which adds to the burden of surgery and may increase morbidity and mortality. Another difference concerns the minimal retraction gap that was found to follow full transection in previous studies.…”

Heterologous spinal cord transplantation in man

“…In 1905, Shirres reported his attempt to graft a segment of healthy canine cord in a human paraplegic patient: initial sensory recuperation was observed at 3 months, but the patient succumbed to infection; of relevance, autopsy showed clear signs of neuroregeneration. [9] is idea bred no further attempts until 40 years later. Woolsey et al [13] in the USA operated on a 16-year-old male with complete loss of sensorimotor function after he was shot in his right shoulder with the bullet reaching the superior border of T4.…”

“…Part and parcel of the GEMINI protocol is polyethylene glycol, a polymer that has been shown to promote angiogenesis in an SCI model. [9] However, vascularization of the donated segment is indicated. By way of illustration, the arterial thoracolumbar territory consists mainly of a ventral (A. spinalis anterior) and two dorsolateral longitudinal trunks (Aa.…”