Emerging drugs for spinal cord injury

被引:43
作者
Baptiste, Darryl C. [3 ]
Fehlingst, Michael G. [1 ,2 ]
机构
[1] Univ Toronto, Toronto, ON M5T 2S8, Canada
[2] Toronto Western Res Inst, Krembil Neurosci Program, Toronto, ON M5T 2S8, Canada
[3] Univ Toronto, Toronto Western Hosp, Univ Hlth Network, Div Neurosurg,Krembil Neurosci Ctr, Toronto, ON M5T 2S8, Canada
关键词
acute spinal cord injury; apoptosis; clinical trials; neuroprotection; regeneration; pharmacological;
D O I
10.1517/14728214.13.1.63
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: This review summarizes several promising pharmacological approaches for the therapeutic management of traumatic spinal cord injury (SCI), which are either in early-phase clinical trials or nearing clinical translation. Objective: This review provides the reader with an understanding of the key pathophysiological mechanisms that contribute to neurological deficits after SCI. Through discussion of the mechanism(s) of action of the selected therapeutic approaches potentially important targets to aid further drug discovery will be highlighted. Methods: Systematic literature review of the pre-clinical literature and clinical SCI trials related to neuroprotective, immunomodulatory and regenerative therapeutic approaches. Results/conclusion: The next decade will witness an unprecedented number of clinical trials which will seek to translate key biomedical research discoveries. The promising drug-based therapeutic approaches include regenerative strategies to neutralize myelin-mediated neurite outgrowth inhibition, neuroprotective strategies to reduce apoptotic triggers, the targeting of cationic/glutamatergic toxicity, anti-inflammatory strategies and the use of approaches to stabilize disrupted cell membranes.
引用
收藏
页码:63 / 80
页数:18
相关论文
共 126 条
[61]  
LACIJF, 2007, J NEUROTRAURNA, V24, P1743
[62]   Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design [J].
Lammertse, D. ;
Tuszynski, M. H. ;
Steeves, J. D. ;
Steeves, J. D. ;
Fawcett, J. W. ;
Rask, C. ;
Ditunno, J. F. ;
Fehlings, M. G. ;
Guest, J. D. ;
Ellaway, P. H. ;
Kleitman, N. ;
Blight, A. R. ;
Dobkin, B. H. ;
Grossman, R. ;
Katoh, H. ;
Privat, A. ;
Kalichman, M. .
SPINAL CORD, 2007, 45 (03) :232-242
[63]   A preliminary study of intravenous surfactants in paraplegic dogs: Polymer therapy in canine clinical SCI [J].
Laverty, PH ;
Leskovar, A ;
Breur, GJ ;
Coates, JR ;
Bergman, RL ;
Widmer, WR ;
Toombs, JP ;
Shapiro, S ;
Borgens, RB .
JOURNAL OF NEUROTRAUMA, 2004, 21 (12) :1767-1777
[64]   Changes of Fas and Fas ligand immunoreactivity after compression trauma to rat spinal cord [J].
Li, GL ;
Farooque, M ;
Olsson, Y .
ACTA NEUROPATHOLOGICA, 2000, 100 (01) :75-81
[65]   Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor [J].
Liu, BP ;
Fournier, A ;
GrandPré, T ;
Strittmatter, SM .
SCIENCE, 2002, 297 (5584) :1190-1193
[66]   Neuroprotection from secondary injury by polyethylene glycol requires its internalization [J].
Liu-Snyder, Peishan ;
Logan, Melissa Peasley ;
Shi, Riyi ;
Smith, Daniel T. ;
Ben Borgens, Richard .
JOURNAL OF EXPERIMENTAL BIOLOGY, 2007, 210 (08) :1455-1462
[67]  
LOU J, 2002, J NEUROCHEM, V83, P471
[68]   The role of inflammation in CNS injury and disease [J].
Lucas, SM ;
Rothwell, NJ ;
Gibson, RM .
BRITISH JOURNAL OF PHARMACOLOGY, 2006, 147 :S232-S240
[69]   Polyethylene glycol improves function and reduces oxidative stress in synaptosomal preparations following spinal cord injury [J].
Luo, J ;
Borgens, R ;
Shi, RY .
JOURNAL OF NEUROTRAUMA, 2004, 21 (08) :994-1007
[70]   Diffusive oxidative stress following acute spinal cord injury in guinea pigs and its inhibition by polyethylene glycol [J].
Luo, J ;
Shi, RY .
NEUROSCIENCE LETTERS, 2004, 359 (03) :167-170