RESEARCH PROFILES

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Gene Therapy

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By Anita Shama
Canadian Spinal Research Organization

The spinal cord makes up part of the central nervous system (CNS). After an injury, damaged nerves in the CNS are unable to repair themselves due to an unfavorable growth environment. The CNS lacks molecules called neurotrophic factors (NTFs), as well as guidance channels and substrates that aid in nerve repair. In addition, the injury induces the release of myelin growth inhibitors, axon degeneration, chronic inflammation, and formation of scar tissue which impedes nerve regrowth. Gene therapy is a method currently being tested to determine whether nerves can regrow across an injured area.

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Cells are removed from the rat. There are two types being used that are available in limitless numbers:

FIBROBLASTS - are skin cells that naturally secrete substrates required for nerve growth

SCHWANN CELLS - are found in the peripheral nervous system. They myelinate peripheral nerves to speed up signal transmission and aid in nerve regeneration by naturally secreting NTFs and substrates.

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NTFs are proteins that can regulate neuron survival and axon growth. There are more than 40 different CNS growth factors. Example: NT-3 (neurotrophin-3) The NTFs are incorporated into viruses which in turn infect the rat cells.

 

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The infected cells have been genetically modified to contain the gene with the neurotrophin which causes them to grow and secrete the NTFs.

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Grafts are created containing numerous fibroblasts or schwann cells. They provide NTFs and substrates that promote nerve growth and survival, as well as an environment free of growth inhibitors. The substrate molecules collagen, fibronectin, and laminin provide a location for the nerves to attach and extend.

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The graft containing the cells are transplanted back into the same rat. This prevents graft rejection since the rats own cells are used. An advantage to this method is that the NTFs are produced and secreted directly into the area of injury.

The same rat that originally had the cells removed would undergo surgery to transect the spinal cord leaving a gap. The grafted cells cause regeneration of motor and sensory neurons. However, different axons have different preferences for various growth substrates and NTFs.