2. Academic Validation
  3. Selective Inhibition of MMP-2 Does Not Alter Neurological Recovery after Spinal Cord Injury

Selective Inhibition of MMP-2 Does Not Alter Neurological Recovery after Spinal Cord Injury

  • ACS Chem Neurosci. 2016 Nov 16;7(11):1482-1487. doi: 10.1021/acschemneuro.6b00217.
Ming Gao 1 2,  Haoqian Zhang 1 2,  Alpa Trivedi 1 2,  Kiran V Mahasenan 1 2,  Valerie A Schroeder 1 2,  William R Wolter 1 2,  Mark A Suckow 1 2,  Shahriar Mobashery 1 2,  Linda J Noble-Haeusslein 1 2,  Mayland Chang 1 2
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry and ‡Freimann Life Sciences Center and Department of Biological Sciences, University of Notre Dame , Notre Dame, Indiana 46556, United States.
  • 2 Department of Neurological Surgery and Physical Therapy and ∥Rehabilitation Science, University of California, San Francisco , San Francisco, California 94143, United States.
PMID: 27551907 DOI: 10.1021/acschemneuro.6b00217
Abstract

Matrix metalloproteinase (MMP)-2 knockout (KO) mice show impaired neurological recovery after spinal cord injury (SCI), suggesting that this proteinase is critical to recovery processes. However, this finding in the KO has been confounded by a compensatory increase in MMP-9. We synthesized the thiirane mechanism-based inhibitor ND-378 and document that it is a potent (nanomolar) and selective slow-binding inhibitor of MMP-2 that does not inhibit the closely related MMP-9 and MMP-14. ND-378 crosses the blood-spinal cord barrier, achieving therapeutic concentrations in the injured spinal cord. Spinal-cord injured mice treated with ND-378 showed no change in long-term neurological outcomes, suggesting that MMP-2 is not a key determinant of locomotor recovery.

Keywords

MMP-2; ND-378; brain distribution; spinal cord injury.

Figures
Products