A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury

Journal of Neurotrauma

Volumn 28, Issue 5, 2011, Pages 787-796

  Fehlings, Michael G ^a   Theodore, Nicholas ^b   Harrop, James ^c   Maurais, Gilles ^d   Kuntz, Charles ^e   Shaffrey, Chris I ^f   Kwon, Brian K ^g   Chapman, Jens ^h   Yee, Albert ^a   Tighe, Allyson ^a   McKerracher, Lisa ^d  

^a UNIVERSITY OF TORONTO   (Canada)

^b BARROW NEUROLOGICAL INSTITUTE   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

^d UNIVERSITÉ DE MONTRÉAL   (Canada)

^e MAYFIELD CLINIC   (United States)

^f UNIVERSITY OF VIRGINIA   (United States)

^g UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^h UNIVERSITY OF WASHINGTON   (United States)

Author keywords

ASIA; Cethrin; clinical trial; motor recovery; Rho

Indexed keywords

CETHRIN; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CLINICAL ARTICLE; COMPUTER ASSISTED TOMOGRAPHY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; IMMUNOASSAY; MALE; NEUROMONITORING; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; SPINAL CORD INJURY; UNSPECIFIED SIDE EFFECT;

ADP RIBOSE TRANSFERASES; ADULT; BOTULINUM TOXINS; ENZYME INHIBITORS; FEMALE; HUMANS; MALE; NEUROPROTECTIVE AGENTS; RECOMBINANT PROTEINS; RECOVERY OF FUNCTION; RHO-ASSOCIATED KINASES; SPINAL CORD INJURIES;

EID: 79955961172     PISSN: 08977151     EISSN: 15579042     Source Type: Journal    
DOI: 10.1089/neu.2011.1765     Document Type: Article

References (29)

1. Anderson, K.D. (2004). Targeting recovery: priorities of the spinal cord-injured population. J. Neurotrauma 21,1371-1383. (Pubitemid 39435314)
2. Bertrand, J., Winton, M.J., Rodriguez-Hernandez, N., Campenot, R.B., and McKerracher, L. (2007). Application of Rho antagonist to neuronal cell bodies promotes neurite growth in compartmented cultures and regeneration of retinal ganglion cell axons in the optic nerve of adult rats. J. Neurosci. 25, 1113-1121. (Pubitemid 40268952)
3. Blight, A.R., and Tuszynski, M.H. (2006). Clinical trials in spinal cord injury. J. Neurotrauma 23, 586-593. (Pubitemid 43726331)
4. Borisoff, J.F., Chan, C.C., Hiebert, G.W., Oschipok, L., Robertson, G.S., Zamboni, R., Steeves, J.D., and Tetzlaff, W. (2003). Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol. Cell Neurosci. 22, 405-416. (Pubitemid 36407602)
5. David, S., and Aguayo, A.J. (1985). Axonal regeneration after crush injury of rat central nervous system fibres innervating peripheral nerve grafts. J. Neurocytol. 14,1-12. (Pubitemid 15075833)
6. Dergham, P., Ellezam, B., Essagian, C., Avedissian, H., Lubell, W.D. and McKerracher, L. (2002). Rho signaling pathway targeted to promote spinal cord repair. J. Neurosci. 22, 6570-6577. (Pubitemid 35386413)
7. Dubreuil, C.I., Winton, M.J., and McKerracher, L. (2003). Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J. Cell Biol. 162, 233-243. (Pubitemid 36928837)
8. Fawcett, J.W., Curt, A., Steeves, J.D., Coleman, W.P., Tuszynski, M.H., Lammertse, D., Bartlett, P.F., Blight, A.R., Dietz, V., Ditunno, J., Dobkin, B.H., Havton, L.A., Ellaway, P.H., Fehlings, M.G., Privat, A., Grossman, R, Guest, J.D., Kleitman, N., Nakamura, M., Gaviria, M., and Short, D. (2007). Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 45,190-205. (Pubitemid 46340848)
9. Fitch, M.T., and Silver, J. (2008). CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209, 294-301. (Pubitemid 351174127)
10. Furlan, J.C., Bracken, M.B., and Fehlings, M.G. (2010). Is age a key determinant of mortality and neurological outcome after acute traumatic spinal cord injury?Neurobiol.Aging, 31, 434-446.
11. Geisler, F.H., Coleman, W.P., Grieco, G., and Poonian, D. (2001). The Sygen multicenter acute spinal cord injury study. Spine 26, S87-S98.
12. Guest, J.D., Hesse, D., Schnell, L, Schwab, M.E., Bunge, M.B., and Bunge, R.P. (1997). Influence of IN-1 antibody and acidic FGF-fibrin glue on the response of injured corticospinal tract axons to human Schwann cell grafts. J. Neurosci. Res. 50, 888-905. (Pubitemid 27518284)
13. Hadley, M.N., Walters, B.C., Grabb, P.A., Oyesiku, N.M., Przybylski, G.J., Resnick, D.K., Ryken, T.C., and Mielke, D.H. (2002). Guidelines for the management of acute cervical spine and spinal cord injuries. Clin Neurosurg.49, 407-498
14. Jin, Z., and Strittmatter, S.M. (1997). Rac1 mediates collapsin-1- induced growth cone collapse. J. Neurosci. 17, 6256-6263. (Pubitemid 27329900)
15. Kassam, A., Nemoto, E., Balzer, J., Rao, G., Welch, W.C., Kuwabara, H., Boada, F., and Horowitz, M. (2004). Effects of Tisseel fibrin glue on the central nervous system of nonhuman primates. Ear Nose Throat J. 83, 246-252.
16. Lehmann, M., Fournier, A., Selles-Navarro, I., Dergham, P., Sebok, A., Leclerc, N., Tigyi, G., and McKerracher, L. (1999). Inactivation of Rho signaling pathway promotes CNS axon regeneration. J. Neurosci. 19, 7537-7547. (Pubitemid 29404610)
17. Li, S., Liu, B.P., Budel, S., Li, M., Ji, B., Walus, L., Li, W., Jirik, A., Rabacchi, S., Choi, E., Worley, D., Sah, D.W., Pepinsky, B., Lee, D., Relton, J., and Strittmatter, S.M. (2004). Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury. J. Neurosci. 24,10,511-10,520. (Pubitemid 39552636)
18. Lord-Fontaine, S., Yang, F., Diep, Q., Dergham, P., Munzer, S., Tremblay, P. and McKerracher, L. (2008). Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury. J. Neurotrauma 25,1309-1322.
19. Mi, S., Lee, X., Shao, Z., Thill, G., Ji, B., Relton, J., Levesque, M., Allaire, N., Perrin, S., Sands, B., Crowell, T., Cate, R.L., Mc- Coy, J.M., and Pepinsky, R.B. (2004). LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat. Neurosci. 7, 221-228. (Pubitemid 38280445)
20. Monnier, P.P., Sierra, A., Schwab, J.M., Henke-Fahle, S., and Mueller, B.K. (2003). The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar Mol. Cell Neurosci. 22,319-330. (Pubitemid 36407595)
21. Nakamura, H., Matsuyama, Y., Yoshihara, H., Sakai, Y., Katayama, Y., Nakashima, S., Takamatsu, J., and Ishiguro, N. (2005). The effect of autologous fibrin tissue adhesive on postoperative cerebrospinal fluid leak in spinal cord surgery: a randomized controlled trial. Spine 30, E347-351.
22. Ramer, L., Borisoff, J., and Ramer, M. (2004). Rho-kinase inhibition enhances axonal plasticity and attenuates cold hyperalgesia after dorsal rhizotomy. J. Neurosci. 24, 10,796-10,805.
23. Richardson, P.M., McGuinness, U.M., Aguayo, AJ. (1980). Axons from CNS neurons regenerate into PNS grafts. Nature 284, 264-265. (Pubitemid 10112047)
24. Rowland, J.W., Hawryluk, G.W., Kwon, B. and Fehlings, M.G. (2008). Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus 25, E2.
25. Sandvig, A., Berry, M., Barrett, L.B., Butt, A., and Logan, A. (2004). Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration. Glia 46, 225-251. (Pubitemid 38679204)
26. Schwab, M.E., Kapfhammer, J.P., and Bandtlow, C.E. (1993). Inhibitors of neurite growth. Annu. Rev. Neurosci. 16, 565-595. (Pubitemid 23074020)
27. Steeves, J.D., Lammertse, D., Curt, A., Fawcett, J.W., Tuszynski, M.H., Ditunno, J.F., Ellaway, P.H., Fehlings, M.G., Guest, J.D., Kleitman, N., Bartlett, P.F., Blight, A.R., Dietz, V., Dobkin, B.H., Grossman, R., Short, D., Nakamura, M., Coleman, W.P., Gaviria, M., and Privat, A. (2007). Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord 45, 206-221. (Pubitemid 46340849)
28. Yamashita, T., Fujitani, M., Yamagishi, S., Hata, K., and Mimura, F. (2005). Multiple signals regulate axon regeneration through the nogo receptor complex. Mol. Neurobiol. 32, 105-111. (Pubitemid 41397179)
29. Yamashita, T., Higuchi, H., and Tohyama, M. (2002). The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J. Cell Biol. 157, 565-570. (Pubitemid 34839785)