Engineering bacterial chondroitinase for expression in mammalian neurons and glia: a strategy for treatment of human brain and spinal cord injury. (360G-Wellcome-079764_Z_06_Z)

£207,908

The main aim of this proposal is to express the bacterial gene for chondroitinase in mammalian neurons and glia, with the ultimate purpose of developing a novel strategy for treating human brain and spinal cord injury. Injection of chondroitinase at the injury site has been shown to promote nerveregeneration by degrading axon growth-inhibitory molecules. Production of the enzyme by cells at the site of injury will make local delivery of the enzyme much more efficient, and we have therefore modified the bacterial gene so thatit can be synthesized and secreted by mammalian cells. We will optimize expression and delivery of the modified cDNA in cultured astrocytes and neurons. We will also generate a construct to provide enzyme with an altered N-terminus to direct secretion to the neuronal growth cone. An in vitro model of axon regeneration will then be used to assess the ability of chondroitinase-transfected astrocytes and neurons to promote axon regeneration. We anticipate that by the end of the project we will be in a position to test the efficacy of the constructs, expressed by neurons and glial cells via an optimized lentiviral vector, in promoting structural and functional regeneration in vivo in rat models of brain and spinal cord.

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Grant Details

Amount Awarded 207908
Applicant Surname Keynes
Approval Committee Molecular and Cellular Neuroscience Funding Committee
Award Date 2006-07-04T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Project Grant
Internal ID 079764/Z/06/Z
Lead Applicant Prof Roger Keynes
Other Applicant(s) Dr Elizabeth Muir, Prof James Fawcett
Partnership Value 207908
Planned Dates: End Date 2010-05-31T00:00:00+00:00
Planned Dates: Start Date 2007-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England