Facilities of Research Excellence in Spinal Cord Injury

Objective

Laboratories around the U.S. and the world are developing spinal cord injury (SCI) research programs and testing novel therapeutic strategies to promote recovery after SCI. It is critical that standard methods are used so that the results from these laboratories be comparable, and translatable to clinical testing. NINDS Facilities of Research Excellence in Spinal Cord Injury (FORE-SCI) contract sites were established to address key factors that have hampered the translation of research on exciting new therapeutic strategies from the laboratory to clinical trials. FORE-SCI sites (1) provide hands-on training to researchers new to SCI research on best practices in the field in order to promote consistency of procedures and animal care across laboratories; (2) attempt to replicate novel experimental therapeutic studies in SCI models, and to compare the efficacy of different treatments in a standardized environment with a minimum of variability in surgery, animal care, outcome evaluation and cellular analyses. In its first iteration, NINDS FORE-SCI sites also supported advance training and collaborative studies, as well as the establishment of novel methods for evaluating recovery in experimental models of spinal cord injury.

Background

Based on a series of workshops, NINDS identified several unmet needs in the field of SCI and, in 2002, developed contracts for FORE-SCI site for training in SCI research methods, replication studies, and development of improved outcome assessments. A report published in 2005 by the Institute of Medicine emphasized the need for continuing instructional and collaborative opportunities in SCI research, specifically citing the training and center supported by the NINDS contract. It is generally agreed that independent replication of preclinical studies is a critical need. Three of the FORE-SCI contracts, therefore, were recompeted in 2008.

Identified barriers to translation include: First, novel and promising results from one laboratory have not been confirmed by replication in other laboratories, or in other model systems. This inability to confirm potentially important outcomes with confidence has prevented new approaches from moving forward to clinical studies. Experience to date demonstrates the difficulty in replicating promising results a number of published reports1, bearing out the need for these demanding studies.

Second, findings from research in other diseases may not be addressed in SCI models because of difficulties in using and maintaining animals. It is a great challenge for researchers to learn the surgical procedures involved in producing these models of SCI, as well as best practices for caring for animals incapacitated by the injury. Implementation of the contract supporting a hands-on training course has had many positive results, including training scientists from laboratories around the world in the rigorous and consistent use of standard surgical (e.g., contusion) models and behavioral measures. (See also the NINDS Workshop Translating Promising Strategies for Spinal Cord Injury Therapy).

Sites and goals

NINDS has funded three FORE-SCI for five years, beginning in late 2008. Three contracts were awarded to the following FORE-SCI sites:

The Ohio State University (OSU) was awarded a contract to continue provide an annual course that trains investigators in methodologies involved in modeling SCI in rodents (PI: Dr. Dana McTigue). OSU was also awarded a new contract to become one of two FORE-SCI replication sites (PI: Dr. Phillip Popovich).

The University of California, Irvine (UCI) was awarded a contract to continue its replications studies (PI: Dr. Oswald Steward). As part of the effort to replicate key studies, both UCI and the OSU may also conduct experiments to compare the efficacy of different individual treatments and treatment combinations for SCI.

¹References

A re-assessment of the consequences of delayed transplantation of olfactory lamina propria following complete spinal cord transection in rats.
Steward O, Sharp K, Selvan G, Hadden A, Hofstadter M, Au E, Roskams J. Exp Neurol. 2006 Apr;198(2):483-99.

A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice.
Steward O, Sharp K, Yee KM, Hofstadter M. Exp Neurol. 2008 Feb;209(2):446-68.

A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model.
Pinzon A, Marcillo A, Quintana A, Stamler S, Bunge MB, Bramlett HM, Dietrich WD. Brain Res. 2008 Dec 3;1243:146-51.