Sergio Canavero’s research while affiliated with First Affiliated Hospital of China Medical University and other places

Dr's Lebenstein-Gumovski's article is devoted to an experiment on the restoration of a transected spinal cord in a large model (pig) using fusogens such as polyethylene glycol (PEG) and chitosan combined in a conjugate (Neuro-PEG). The combined approach made it possible to achieve significant success in the study.

Despite the conventional belief that motor function and sensation distal to the site of a complete spinal cord transection are irretrievable, our research has demonstrated significant motor recovery in mice, rats, and dogs by applying polyethylene glycol (PEG) directly onto the transection site of the spinal cord. However, before implementing this technology in human subjects, validating PEG’s efficacy and enduring impact through experimentation on non-human primates is imperative. Two 4-year-old female Macaca fascicularis monkeys underwent complete dorsal cord transection at T10. Postoperative behavioral assessment, electrophysiologic monitoring, and neuroimaging examinations were recorded, and tissues were obtained for histological examination at the end of study. The monkey whose spinal cord had been fully transected in the presence of PEG developed useful recovery already at 3 months and near-complete recovery of motor function in the hind-limbs at 18 months. The control animal without PEG remained paralyzed. Cortical somatosensory evoked potentials recovered postoperatively only in PEG-treated monkey vs none in the control. Diffusion tensor imaging showed re-establishment of continuity of the white matter in PEG-treated monkey, but not in the control. Moreover, histology revealed intact neuronal bodies, axons, and myelin tissue at the spinal cord transection site in PEG-treated monkey only. This report suggests that in primates, an acutely transected spinal cord can be re-fused in the presence of PEG with restoration of neural continuity and functional recovery of motor activity distal to the site of transection.

There is at present no biological cure for chronic paralysis following spinal cord injury (SCI). Work conducted by U.S. neurosurgeon L. Walter Freeman in the 1960s suggests that a permanent, biological cure is possible, at least in several cases of chronic SCI, by removing the most damaged portion of the spinal cord en bloc, and connecting the two free undamaged ends, after spinal (vertebral) shortening. Alternatively, we recently suggested filling the post-extirpation gap with a segment of normal cord. In both cases, a technology that allows the functional reconnection of the severed ends is necessary. The GEMINI spinal cord fusion (SCF) protocol described for the first time in 2013 is such technology. We briefly review the components of the GEMINI protocol and describe its application in the context of the first clinical trial testing autologous cord grafting in chronic SCI patients (Shirres-GEMINI approach).

Aim Despite animal evidence of a role of calcium in the pathogenesis of spinal cord injury, several studies conducted in the past found calcium blockade ineffective. However, those studies involved oral or parenteral administration of Ca++ antagonists. We hypothesized that Ca++ blockade might be effective with local/immediate application (LIA) at the time of neural injury. Methods In this study, we assessed the effects of LIA of BAPTA (1,2‐bis (o‐aminophenoxy) ethane‐N, N, N′, N'‐tetraacetic acid), a cell‐permeable highly selective Ca++ chelator, after spinal cord transection (SCT) in mice over 4 weeks. Effects of BAPTA were assessed behaviorally and with immunohistochemistry. Concurrently, BAPTA was submitted for the first time to multimodality assessment in an in vitro model of neural damage as a possible spinal neuroprotectant. Results We demonstrate that BAPTA alleviates neuronal apoptosis caused by physical damage by inhibition of neuronal apoptosis and reactive oxygen species (ROS) generation. This translates to enhanced preservation of electrophysiological function and superior behavioral recovery. Conclusion This study shows for the first time that local/immediate application of Ca++ chelator BAPTA is strongly neuroprotective after severe spinal cord injury.

Background: Our study shows that a membrane sealant/fiber fusogen polyethylene glycol (PEG) applied immediately on a sharp section of the spinal cord can mend the cord and lead to exceptional levels of motor recovery, with some animals almost normal. Materials and methods: Before deploying such technology in man, long-term data in large mammals that exclude delayed complications (e.g., central pain), confirm the stability of motor recovery, and provide histological evidence of fiber regrowth are necessary. Here, we provide such evidence in dogs followed up over 6 months and in 2 cases up to 1 year along with imaging and histologic data. Results: We show that dogs whose dorsal cord has been fully transected recover locomotion after immediate treatment with a fusogen (PEG). No pain syndrome ensued over the long term. Diffusion tensor imaging magnetic resonance and histological, including immunohistochemical, data confirmed the re-establishment of anatomical continuity along with interfacial axonal sprouting. Conclusions: This study proves that a form of irreversible spinal cord injury (SCI) can effectively be treated and points out a way to treat SCI patients.

A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when prepared as 1wt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1 (L1) level. In vivo and in vitro experiments (n = 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200 (NF200) antibody and astrocytic scar marker glial fibrillary acidic protein (GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SY5Y cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that TexasPEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.