Bridging the gap: from discovery to clinical trials in spinal cord injury.

Recently, the Kent Waldrep National Paralysis Foundation initiated a think tank intended to bridge several gaps and achieve several goals in regard to spinal cord injury (SCI) research and funding. Affiliated with the need to bridge a pathophysiological gap in spinal parenchyma and/or reorganize remaining circuitry after injury is a need to bridge resource gaps for timely funding for translational research, gaps in knowledge between researchers, and between researchers/clinicians and SCI patients. The epistemology of cure was examined and redefined to include transitional recoveries and advances. Modes and mechanisms of funding have been evaluated and where deficits were perceived, suggestions have been made to expedite and increase the number and breadth of funding opportunities. Innovative infrastructure changes are submitted. We discuss the progression of clinical trials as well as offer suggestions to facilitate benchtop-to-bedsite translation of valuable research to the customer. Highlights of recently completed, in progress, and future trials are detailed. Finally, we submit five essential processes required to promote advances to the SCI patient population: discovery, development, clinical trials, evaluation, and rehabilitation. These ideas are intended to facilitate entry of serious dialogue and to ultimately improve the lives of patients living with SCI.

[1]  C. Sherrington Flexion‐reflex of the limb, crossed extension‐reflex, and reflex stepping and standing , 1910, The Journal of physiology.

[2]  J. Parlange,et al.  Water uptake, diameter change, and nonlinear diffusion in tree stems. , 1975, Plant physiology.

[3]  S. Grillner Locomotion in vertebrates: central mechanisms and reflex interaction. , 1975, Physiological reviews.

[4]  A. Bricolo,et al.  Local cooling in spinal cord injury. , 1976, Surgical neurology.

[5]  J. A. Tanner,et al.  Current Status of Spinal Cord Cooling in the Treatment of Acute Spinal Cord Injury , 1984, Spine.

[6]  T. Bajd,et al.  Pendulum testing of spasticity. , 1984, Journal of biomedical engineering.

[7]  Hall Ed,et al.  Non-surgical management of spinal cord injuries: a review of studies with the glucocorticoid steroid methylprednisolone. , 1987 .

[8]  N. Alessi,et al.  Amitriptyline supersensitizes a central cholinergic mechanism , 1987, Biological Psychiatry.

[9]  R. Betz,et al.  Post-traumatic spinal cord cysts evaluated by magnetic resonance imaging , 1991, Paraplegia.

[10]  F. Geisler,et al.  Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside. , 1991, The New England journal of medicine.

[11]  Sandford Pr,et al.  Amitriptyline and carbamazepine in the treatment of dysesthetic pain in spinal cord injury. , 1992 .

[12]  F. Geisler,et al.  GM-1 ganglioside in human spinal cord injury. , 1992, Journal of neurotrauma.

[13]  W. Collins,et al.  Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. , 1992, Journal of neurosurgery.

[14]  M. Bracken,et al.  The Second National Acute Spinal Cord Injury Study. , 1990, Journal of neurotrauma.

[15]  D. Wolfe,et al.  Effects of induced hypothermia on somatosensory evoked potentials in patients with chronic spinal cord injury , 1993, Paraplegia.

[16]  T. Holford,et al.  Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-tract neurological function in NASCIS 2. , 1993, Journal of neurosurgery.

[17]  P. Jacobs,et al.  Involuntary stepping after chronic spinal cord injury. Evidence for a central rhythm generator for locomotion in man. , 1994, Brain : a journal of neurology.

[18]  D. Wolfe,et al.  4-Aminopyridine-sensitive neurologic deficits in patients with spinal cord injury. , 1994, Journal of neurotrauma.

[19]  R. Smith,et al.  Intrathecal baclofen for treatment of intractable spinal spasticity. , 1994, Archives of physical medicine and rehabilitation.

[20]  L. Goldstein,et al.  Common drugs may influence motor recovery after stroke , 1995, Neurology.

[21]  J. Micó,et al.  Test-dependent relationship of the antidepressant and analgesic effects of amitriptyline. , 1995, Methods and findings in experimental and clinical pharmacology.

[22]  J. Olesen,et al.  Amitriptyline, a combined serotonin and noradrenaline re-uptake inhibitor, reduces exteroceptive suppression of temporal muscle activity in patients with chronic tension-type headache. , 1996, Electroencephalography and clinical neurophysiology.

[23]  M. Wilde,et al.  Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. , 1996, Drugs & aging.

[24]  Yihai Cao,et al.  Spinal Cord Repair in Adult Paraplegic Rats: Partial Restoration of Hind Limb Function , 1996, Science.

[25]  B. Bussel,et al.  Intrathecal baclofen administration for control of severe spinal spasticity: functional improvement and long-term follow-up. , 1996, Archives of physical medicine and rehabilitation.

[26]  Robert G. Godfrey,et al.  A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes. , 1996, Archives of internal medicine.

[27]  Douglas K. Anderson,et al.  Characteristics of Human Fetal Spinal Cord Grafts in the Adult Rat Spinal Cord: Influences of Lesion and Grafting Conditions , 1997, Experimental Neurology.

[28]  Aqing Chen,et al.  Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord , 1997, Journal of neurocytology.

[29]  S. Whittemore,et al.  Gene therapy and the use of stem cells for central nervous system regeneration. , 1997, Advances in neurology.

[30]  C. Hulsebosch,et al.  Transplant therapy: recovery of function after spinal cord injury. , 1997, Journal of neurotrauma.

[31]  C. Hulsebosch,et al.  Chronic central pain after spinal cord injury. , 1997, Journal of neurotrauma.

[32]  B. Dobkin,et al.  Human lumbosacral spinal cord interprets loading during stepping. , 1997, Journal of neurophysiology.

[33]  H. Winn,et al.  Administration of Methylprednisolone for 24 or 48 Hours or Tirilazad Mesylate for 48 Hours in the Treatment of Acute Spinal Cord Injury Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial , 1997 .

[34]  O. Ringdén,et al.  Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt. , 1997, Journal of neurotrauma.

[35]  V R Edgerton,et al.  Use-dependent plasticity in spinal stepping and standing. , 1997, Advances in neurology.

[36]  V. Reggie Edgerton,et al.  Does Motor Learning Occur in the Spinal Cord? , 1997 .

[37]  J. Wrathall,et al.  Delayed Antagonism of AMPA/Kainate Receptors Reduces Long-Term Functional Deficits Resulting from Spinal Cord Trauma , 1997, Experimental Neurology.

[38]  F. Geisler Clinical Trials of Pharmacotherapy for Spinal Cord Injury , 1998, Annals of the New York Academy of Sciences.

[39]  A. Wernig,et al.  Maintenance of locomotor abilities following Laufband (treadmill) therapy in para- and tetraplegic persons: follow-up studies , 1998, Spinal Cord.

[40]  C. Hellerqvist,et al.  CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[41]  M. Schwartz,et al.  Restricted inflammatory reaction in the CNS: a key impediment to axonal regeneration? , 1998, Molecular medicine today.

[42]  M. Schwartz,et al.  Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats , 1998, Nature Medicine.

[43]  J. Mountz,et al.  A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin , 1998, Pain.

[44]  M. C. Acosta,et al.  Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. , 1999, Journal of neurotrauma.

[45]  P. Strojnik,et al.  A custom designed chip to control an implantable stimulator and telemetry system for control of paralyzed muscles. , 1999, Artificial organs.

[46]  J. Segal,et al.  Safety and Efficacy of 4‐Aminopyridine in Humans with Spinal Cord Injury: A Long‐Term, Controlled Trial , 1999, Pharmacotherapy.

[47]  M. Schwartz,et al.  Innate and adaptive immune responses can be beneficial for CNS repair , 1999, Trends in Neurosciences.

[48]  J. Wrathall,et al.  2,3-Dihydroxy-6-Nitro-7-Sulfamoyl-Benzo(f)Quinoxaline Reduces Glial Loss and Acute White Matter Pathology after Experimental Spinal Cord Contusion , 1999, The Journal of Neuroscience.

[49]  M. Ashburn,et al.  Management of chronic pain , 1999, The Lancet.

[50]  M. Murray,et al.  Intraspinal Delivery of Neurotrophin-3 Using Neural Stem Cells Genetically Modified by Recombinant Retrovirus , 1999, Experimental Neurology.

[51]  M. Eaton,et al.  Lumbar transplant of neurons genetically modified to secrete galanin reverse pain-like behaviors after partial sciatic nerve injury. , 1999, Journal of the peripheral nervous system : JPNS.

[52]  P. Safar,et al.  Therapeutic hypothermia in traumatology. , 1999, The Surgical clinics of North America.

[53]  M. Esser,et al.  Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat , 1999, Pain.

[54]  A. Stavros,et al.  Surgical treatment of posttraumatic cystic and tethered spinal cords. , 1999, The journal of spinal cord medicine.

[55]  A. Wernig,et al.  Laufband (treadmill) therapy in incomplete paraplegia and tetraplegia. , 1999, Journal of neurotrauma.

[56]  J. Mcdonald,et al.  Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord , 1999, Nature Medicine.

[57]  M. Murray,et al.  DNA plasmid that codes for human Bcl‐2 gene preserves axotomized Clarke's nucleus neurons and reduces atrophy after spinal cord hemisection in adult rats , 1999, The Journal of comparative neurology.

[58]  M. Leathley,et al.  Reliability of the Tone Assessment Scale and the modified Ashworth scale as clinical tools for assessing poststroke spasticity. , 1999, Archives of physical medicine and rehabilitation.

[59]  R. Sewell,et al.  Do alpha2-adrenoceptors play an integral role in the antinociceptive mechanism of action of antidepressant compounds? , 1999, European journal of pharmacology.

[60]  C. Hulsebosch,et al.  Transplants of Adrenal Medullary Chromaffin Cells Reduce Forelimb and Hindlimb Allodynia in a Rodent Model of Chronic Central Pain after Spinal Cord Hemisection Injury , 2000, Experimental Neurology.

[61]  H Barbeau,et al.  The role of rehabilitation in the recovery of walking in the neurological population , 2001, Current opinion in neurology.

[62]  C. Hulsebosch,et al.  Subdural engraftment of serotonergic neurons following spinal hemisection restores spinal serotonin, downregulates serotonin transporter, and increases BDNF tissue content in rat , 2001, Brain Research.