Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury

Abstract

<jats:p>Over the past 2 decades, advances in understanding the pathophysiology of spinal cord injury (SCI) have stimulated the recent emergence of several therapeutic strategies that are being examined in Phase I/II clinical trials. Ten randomized controlled trials examining methylprednisolone sodium succinate, tirilizad mesylate, monosialotetrahexosylganglioside, thyrotropin releasing hormone, gacyclidine, naloxone, and nimodipine have been completed. Although the primary outcomes in these trials were laregely negative, a secondary analysis of the North American Spinal Cord Injury Study II demonstrated that when administered within 8 hours of injury, methylprednisolone sodium succinate was associated with modest clinical benefits, which need to be weighed against potential complications. Thyrotropin releasing hormone (Phase II trial) and monosialotetrahexosylganglioside (Phase II and III trials) also showed some promise, but we are unaware of plans for future trials with these agents. These studies have, however, yielded many insights into the conduct of clinical trials for SCI. Several current or planned clinical trials are exploring interventions such as early surgical decompression (Surgical Treatment of Acute Spinal Cord Injury Study) and electrical field stimulation, neuroprotective strategies such as riluzole and minocycline, the inactivation of myelin inhibition by blocking Nogo and Rho, and the transplantation of various cellular substrates into the injured cord. Unfortunately, some experimental and poorly characterized SCI therapies are being offered outside a formal investigational structure, which will yield findings of limited scientific value and risk harm to patients with SCI who are understandably desperate for any intervention that might improve their function. Taken together, recent advances suggest that optimism for patients and clinicians alike is justified, as there is real hope that several safe and effective therapies for SCI may become available over the next decade.</jats:p>

Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

“…The ultrastructure of hydrogel was investigated using SEM. Representative micrographs showed that the macroporous hydrogel had communicating pores (2 3 10 6 pores per cm 3 ) with an average size of 80 mm and a specific pore volume of 0.45 (Figure 1c, d).…”

“…Clinical treatment may involve intravenous administration of the steroid methylprednisolone; however, the efficacy of this approach has been widely disputed 1 . Several clinical trials have also been completed using pharmacological agents 2,3 ; however, no trials have shown effective regulation of axonal regeneration. Tissue engineering techniques, which are focused on promoting the regeneration of injured nervous tissue, continue to assume greater importance in neuroscience.…”

Emerging Approaches to the Surgical Management of Acute Traumatic Spinal Cord Injury

“…Economic data from the United States National Institute of Neurological Disorders and Stroke reports that approximately $4 billion dollars are spent annually in the acute treatment and chronic care of spinal cord injured individuals [4]. In spite of the immense impact of SCI at a personal and societal level, uniform treatment strategies aimed at attenuating the initial degree of neurologic injury and reducing patients' future dependency are lacking [5].…”

Cytoprotective activity of minocycline includes improvement of mitochondrial coupling: the importance of minocycline concentration and the presence of VDAC

“…Fagan et al 2010;Gupta and Chauhan 2011) as well as spinal cord and traumatic brain injury (e.g. Wang et al 2006;Hawryluk et al 2008). It is concluded that the cytoprotective capability of minocycline results from its anti-inflammatory, anti-apoptotic, and antioxidant properties (e.g.…”