The SCI Research Front

1. Frontiers in Spinal Cord Injury Therapies Kim Anderson-Erisman, Ph.D. Director of Education The Miami Project to Cure Paralysis University of Miami July 12, 2011

3. 61% malesModel Systems for SCI Chris & Dana Reeve Foundation

4. Life Expectancy & Costs of SCI

5. Types of SCI

6. What is Spinal Cord Injury (SCI)? Normal Solid cord damage Contusion w/ cyst Laceration Massive Compression Norenberg et al., 2004. J. Neurotrauma. 21:429-440

7. Inside the spinal cord Inhibitory scar Cut axons Primary damage Secondary damage Cell death McDonald , 1999. Sci. Amer. 281:64-73

9. Legs

10. Arms/hands

11. Abdominal/Intercostal

12. Sphincters

13. Sensory

14. Light touch

15. Pin prick

16. Temperature

17. Spontaneous pain

18. Autonomic

19. Cardiovascular

20. Temperature regulation

21. Bladder

22. Bowel

24. Repair Strategies Neutralize inhibitory scar Induce axon regeneration Prevent secondary damage Cell replacement McDonald , 1999. Sci. Amer. 281:64-73

25. Clinical Trials COST The majority of academic research is in the “Pre-Discovery” and “Discovery” phases. 30 days

27. Riluzole (NACTN)

28. Already FDA-approved for Lou Gehrig’s disease (ALS)

29. Phase I safety study; multi-center

30. Within 12 hrs post-injury, continue for 14 days; Oral

31. Minocycline (University of Calgary)

32. Phase I/II safety & preliminary efficacy; single center

33. Within 12 hrs post-injury, continue for 7 days; IV

34. Cethrin (BA-210; Alseres Pharmaceuticals)

35. Previous Phase I & II trials

38. Geron Corp.; multi-center

39. Phase I safety study of GRNOPC1

40. Human embryonic stem cell line pre-differentiated into oligodendrocyte progenitor cells

41. Targeting remyelination of demyelinated axons to restore conduction

42. Complete thoracic spinal cord injury

43. Within 14 days of injury

44. Intraspinal injection; single dose

45. Temporary immunosuppression

46. Follow for 1 year intensely, then 15 years long-termCell-based Keirstead et al., 2005 J. Neurosci. 29(19):4694

48. StemCells, Inc.; single center

49. Phase I/II safety & preliminary effiacy of HuCNS-SC

50. Human neural stem cells derived from fetal brain tissue

51. Targeting remyelination and possibly neuronal cell replacement

52. Complete and incomplete thoracic SCI (3 cohorts)

53. Within 3 to 12 months post-injury

54. Intraspinal injection

55. Temporary immunosuppression

56. Follow for 1 year intensely, then 4 years long-termCell-based cont’d

58. Memorial Hermann Healthcare System/ UT Health Science Center; single center

59. Phase I safety study of huBMPCs

60. Harvested from bone marrow

61. Target not define, possibly a growth supportive role by releasing neurotrophic chemicals

62. Complete and incomplete SCI; 1-15 years of age

63. Within 6 months to 4 years post-injury

64. Intravenous injection; single dose

65. Autologous (no immunosuppression)

66. Follow for 6 months, then 1.5 years long-termCell-based cont’d

67. Human Schwann cells The Miami Project/University of Miami Preparing IND for proposed Phase I safety study Harvested from sural nerve biopsy Targeting remyelination and neurotrophic support Complete, thoracic SCI Within 5 days post-injury Intraspinal injection; single dose Autologous (no immunosupression) Follow for 1 year intensely, then TBD long-term Cell based cont’d

68. AT1355 Novartis; multi-center in US, Canada, and Europe Phase I safety study of Nogo antibody AT1355 Human antibody to Nogo protein Targeting nerve fiber sprouting indirectly by neutralizing the inhibitory effects of damaged myelin Complete SCI, C5-T12 Within 4 to 14 or 28 days post-injury Intrathecal infusion; 6 dose cohorts Follow for 1 year Neutralize inhibition Schwab 2010 Nat. Rev. Neurosci. 11:799-811

69. Axonal Regeneration

71. Effectiveness of Automated Locomotor Training in Patients With Acute Incomplete Spinal Cord Injury: A Multicenter Trial

72. SCIPA (Spinal Cord Injury and Physical Activity) Hands-On: Early Intensive Hand Rehabilitation After Spinal Cord Injury

73. SCIPA Full-On :Intensive Exercise Program After Spinal Cord Injury

74. Study on Functional Electrical Stimulation (FES) Cycling Following Spinal Cord Injury

75. Patterned Functional Electrical Stimulation (FES) Ergometry of Arm and Shoulder in Individuals With Spinal Cord Injury

76. Implanted Myoelectric Control for Restoration of Hand Function in Spinal Cord Injury

78. The Effect of an Exercise Program on Physical Function After a Spinal Cord Injury

79. The Effect of Locomotor Training on Children With Incomplete Spinal Cord Injuries

80. Enhancing Walking in People With Incomplete Spinal Cord Injury: a Pilot Study

81. The Effects of Passive Gait Training in Complete Motor Spinal Cord Injury (SCI)

82. Improving Hand and Arm Function After Spinal Cord Injury (SCI)

83. Effect of Vibration Therapy on Bone in Persons With Sub-acute Spinal Cord Injury

85. The Effects of Two Functional Electrical Stimulation Cycling Paradigms

86. Effects of an Early Wheelchair Reconditioning Program on Functional Independence in spinal cord-injured Individuals

87. FES Therapy: Restoring Voluntary Grasping Function in Chronic SCI

88. Effects of Exercise in People With Tetraplegia

89. Effects of Exercise in People With Paraplegia

90. Functional and Physiological Responses to Lokomat Therapy (Pilot Study)Rehabilitation

91. Ultimate “Cure” Neuroprotective intervention early Cell replacement therapy (single or multiple types of cells) Axonal regeneration therapies Muscle conditioning and bone density maintenance throughout Specific motor training paradigms

92. Questions