Identification of novel molecules in blocking chondroitin sulphate proteoglcyans inhibition
Funded in: 2012, 2013, 2014
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The presence of chondroitin sulfate proteoglycans (CSPGs) strongly limits the functional recovery after a spinal cord injury (SCI). CSPGs act in two ways:
- First they are constantly present in the healthy tissue as part of the so-called perineuronal nets (PNNs). It has been shown that their presence (although limited to only 2% of the whole PNNs composition) limits the plasticity of undamaged fibres after SCI.
- Second, CSPGs’ expression increases in the glial scar at the injury site, actively inhibiting axonal regeneration and functional recovery.
CSPGs can be degraded with chondroitinase ABC (ChABC). However, due to the enzymatic nature of chondroitinase ABC, the injection has to be done intra-parenchymally which is both, difficult and invasive.
Dr. Kwok aims at developing new, safer and more practical methods for blocking CSPG-operated growth inhibition. Since CSPGs exert their inhibition through the sulfation motifs, strategies to block CSPGs effect will include:
- Testing antibodies and a lectin that block the motifs themselves and
- Changing expression of the sulfation enzymes that produce these motifs
The ultimate goal is to develop the next generation of treatment, which will be clinically more relevant and might have better chances to be one day applied in human subjects.