Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic and Urologic Recovery after Spinal Cord Injury
Posted January 3, 2013
Linda Noble, Ph.D. University of California, San Francisco
Jonathan Levine, DVM, Texas A & M
Despite decades of effort being dedicated to developing therapeutics for spinal cord injury (SCI), a robust clinical treatment remains elusive. Following acute SCI, matrix metalloproteinases (MMPs) are upregulated and promote early inflammation and disrupt the extracellular matrix (ECM) and the blood-spinal cord barrier. Dr. Linda Noble has received a Fiscal Year 2010 Investigator-Initiated Research Award to study the efficacy of an MMP inhibitor in a mouse model of SCI as well as a larger animal model with naturally occurring SCIs as the result of spontaneous rupture of an intervertebral disk. Newly completed studies in mice subjected to a relatively severe SCI show that the MMP inhibitor therapy, when given 8 hours post injury, results in improved neurological outcome by 6 weeks. Moreover, bladder function, assayed by awake cystometry, is also improved as evidenced in part by a reduction in uninhibited bladder contractions and residual urine. Dr. Noble has entered into collaboration with Dr. Jon Levine at Texas A&M University to determine the efficacy of the MMP inhibitor in a second animal model of SCI. The safety and appropriate drug dosing parameters of the MMP inhibitor have been established in uninjured animals. Baseline urodynamic data have been collected in both uninjured animals and animals with acute SCI. The unique two species design of this study will enable the rapid preclinical optimization of a promising MMP inhibitor for the treatment of SCI. If these preclinical studies in animal models are successful, this compound could be quickly transitioned into human clinical trials.
Links:
Public and Technical Abstracts: Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic Recovery after Spinal Cord Injury
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