Overcoming the sprouting limit of axons in the brain – using biomaterials for the treatment of Parkinson’s disease

Current pharmacological or surgical therapies for Parkinson’s disease (PD) offer only symptomatic relief.

The loss of neurons continues inexorably until the disease reaches its conclusion. Therefore new ways are being explored to prevent ongoing neuronal degeneration and to restore functional pathways. Cell transplantation is a potentially effective treatment strategy for PD. However for the success of this strategy, the implanted neurons must form sufficient and appropriate synaptic connections. A major obstacle to this success is that the adult brain does not i) provide adequate trophic support, resulting in poor engraftment and ii) provide guidance cues that promote growth of new neuronal fibres over significant distances, to restore the hosts neural circuitry.  This project builds upon our published and preliminary data and utilises a cross-disciplinary approach, using an injectable hybrid matrix based exclusively on FDA-approved biodegradable biomaterials. The hybrid matrix is designed to assist implanted dopaminergic (DA) neurons to survive and bridge the nigrostriatal neural pathway in the brain, which deteriorate as a consequence of PD.   Our research project builds upon recent research findings, which demonstrate that our novel matrix:  1) provides a favourable 3-dimensional cellular microenvironment,  2) has a minimal inflammatory footprint and integrates seamlessly into the brain and  3) provides functional recovery when used in conjunction with DA neurons in a mouse model of PD.   We therefore seek to use our cell-matrix construct and demonstrate functional recovery in animal models.   Figure text:  An injectable matrix is implanted beside the nigrostriatal tract to improve engraftment and provide axonal guidance cues for implanted DA neurons to reach their target. The distance in mouse is 5mm, marmoset 10mm and human 30mm.