Antisense Technology for Neural Protection and Repair

Spinal Cord Injury (SCI) is a devastating condition for which there is no effective treatment. The cost to society is enormous because most new cases occur in people under the age of 30 and these individuals have a near normal life expectancy. Therefore, the development of a new, effective therapy to treat SCI is imperative. We propose to use an established in vitro assay to screen antisense molecules for neural protection. Primary cultures of rat central nervous (CNS) tissue consisting of neurons, astrocytes, and microglial cells will be established. These mixed CNS cultures will be injured by addition of the cytokine IL- 1, glutamate or by mechanical injury. Taken together, these injuries mimic important aspects of SCI. Using current technology, antisense sequences will be designed and synthesized to inhibit the production of various proteins that have been shown to be involved in tissue damage following neural injury. These antisense sequences will be added to injured CNS cultures and neuroprotective activity will be assessed. As a result of this screening protocol, we expect to identify a small list of antisense molecules that demonstrate efficacy and warrant additional studies of equivalent human sequences in the appropriate pre-clinical models of SCI. Ultimately, we expect to identify a candidate molecule, which Acorda Therapeutics can take to human clinical trials for the treatment of SCI and related conditions. PROPOSED COMMERCIAL APPLICATIONS: The financial cost for the care of patients with spinal cord injury and neurodegenerative diseases in the US alone has been estimated to be in excess of $90 billion annually. Any therapeutic agent developed and commercialized as a result of this proposal will have a profound, positive impact on the lives of patients with neurodegenerative disease.