Spinal cord injury (SCI) can lead to paraplegia or quadriplegia. Although there are no fully restorative treatments for SCI, various rehabilitative, cellular and molecular therapies have been tested in animal models. Many of these have reached, or are approaching, clinical trials. Here, we review these potential therapies, with an emphasis on the need for reproducible evidence of safety and efficacy. Individual therapies are unlikely to provide a panacea. Rather, we predict that combinations of strategies will lead to improvements in outcome after SCI. Basic scientific research should provide a rational basis for tailoring specific combinations of clinical therapies to different types of SCI.

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Therapeutic interventions after spinal cord injury.

From basics to clinical: a comprehensive review on spinal cord injury.

OBJECTIVE: To provide a comprehensive review of the treatment trials in the field of spinal cord injury, emphasizing what has been learned about the effectiveness of the agents and strategies tested and the quality of the methodology. The review aims to provide useful information for the improvement of future trials. The review audience includes practitioners, researchers, and consumers. METHODS: All publications describing organized trials since the 1960s were analyzed in detail, emphasizing randomized, prospective controlled trials and published Phase I and II trials. Trials were categorized into neuroprotection, surgery, regeneration, and rehabilitation trials. Special attention was paid to design, outcome measures, and case selection. RESULTS: There are 10 randomized prospective control trials in the acute phase that have provided much useful information. Current neurological grading systems are greatly improved, but still have significant shortcomings, and independent, trained, and blinded examiners are mandatory. Other trial designs should be considered, especially those using adaptive randomization. Only methylprednisolone and thyrotropin-releasing hormone have been shown to be effective, but the results of the former are controversial, and studies involving the latter involved too few patients. None of the surgical trials has proven effectiveness. Currently, a multitude of cell-based Phase I trials in several countries are attracting large numbers of patients, but such treatments are unproven in effectiveness and may cause harm. Only a small number are being conducted in a randomized or blinded format. Several consortia have committed to a promise to improve the conduct of trials. CONCLUSION: A large number of trials in the field of spinal cord injury have been conducted, but with few proven gains for patients. This review reveals several shortcomings in trial design and makes several recommendations for improvement.

Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations.

https://journals.sagepub.com/doi/pdf/10.3727/096368912X663532

Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury.

Background. In China, fetal brain tissue has been transplanted into the lesions of more than 400 patients with spinal cord injury (SCI). Anecdotal reports have been the only basis for assuming that the procedure is safe and effective. Objective. To compare available reports to the experiences and objective findings of patients who received pre-operative and postoperative assessments before and up to 1 year after receiving cellular implants. Methods. Independent observational study of 7 chronic SCI subjects undergoing surgery by Dr Hongyun Huang in Beijing. Assessments included lesion location by magnetic resonance imaging, protocol of the American Spinal Injury Association (ASIA), change in disability, and detailed history of the perioperative course. Results. Inclusion and exclusion criteria were not clearly defined, as subjects with myelopathies graded ASIA A through D and of diverse causes were eligible. Cell injection sites did not always correlate with the level of injury and included the frontal lob...

/pdf/cellular-transplants-in-china-observational-study-from-the-43isf38xzb.pdf

Cellular Transplants in China: Observational Study from the Largest Human Experiment in Chronic Spinal Cord Injury:

Objective To evaluate the restoration of function after spinal cord injury (SCI) in patients of different ages who have underwent intraspinal transplantation of olfactory ensheathing cells ( OECs). Methods One hundred andseventy-one SCI patients were included in this study. Of them, 139 were male and 32 were female, with age ranging from 2 to 64 years ( mean, 34. 9 years). In all SCI patients the lesions were injected at the time of operation with OECs. According to their ages, the patients were divided into 5 groups: ≤20 years group (n =9), 21 -30 years group (n = 54), 31 -40 years group (n=60), 41 -50 years group (n=34) and >51 years group (n = 14). The spinal cord function was assessed based on the American Spinal Injury Association (ASIA) Classification System before and 2 - 8 weeks after OECs transplantation. One-way ANOVA and q test were used for statistical analysis, and the data were expressed as mean ′ SD. Results After surgery, the motor scores increased by 5. 2 ′ 4.8, 8.6 ′ 8.0, 8. 3 ′ 8.8, 5.7 ′ 7.3 and 8. 2 ′7. 6 in 5 age groups respectively (F=1.009, P = 0. 404); light touch scores increased by 13.9 ′ 8.1, 15.5 ′ 14.3, 12.0 ′ 14.4, 14. 1 ′ 18.5 and 24.8 ′ 25.3 respectively (F=1.837, P= 0. 124); and pin prick scores increased by 11.1 ′ 7.9, 17. 2 ′ 14.3, 13. 2 ′ 11., 13. 6 ′ 13.9 and 25.4 ′ 24.3 respectively (F=2.651, P =0.035). Restoration of pin prick in >51 years group was better than other age groups except 21 -30 years group. Conclusion OECs transplantation can improve the neurological function of spinal cord of SCI patients regardless of their ages. Further research into the long-term outcomes of the treatment will be required.

Rui Wang

Papers

Influence of patients' age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury.