Spinal cord injury (SCI) is a debilitating condition that often results in major neurological deficits. Surgical decompression, rehabilitation, and prevention of complications have improved the outcome in SCI, but currently there is no effective treatment for enhancing neurological function in chronic patients. Fifteen years ago, chondroitinase ABC (chABC), a bacterial enzyme, was shown to improve neurological function in animal models of SCI. However, for several reasons, there has been no translation of this promising therapy to SCI in humans because of the enzyme’s thermal instability, and uncertainty about how, where, and for how long to administer the agent.
There is no consensus on the optimal location and duration of chABC administration. The present proposal examines the efficacy and safety of a unique formulation of sustained release enzyme termed SR-chABC which for the first time allows local sustained release. Two clinically feasible methods of administration of SR-chABC will be compared including minimally invasive lumbar puncture which is highly translatable. Furthermore, the proposed studies will be performed in a clinically relevant rat model of chronic SCI. Importantly, we are a highly experienced team capable of performing all the proposed studies based on several years of work in SCI with the following expertise: 1) manufacture of SR-chABC; 2) delivery of the agent to the injured rat spinal cord in a clinically relevant model of chronic SCI; 3) delivery of the agent to small animals utilizing routes relevant to humans with chronic SCI; and 4) use of minimally invasive delivery techniques based on modern bioengineering. The proposed studies are essential for translating the chABC strategy to humans with chronic SCI.
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