Principal Investigator: Dave Lin

DESCRIPTION (provided by applicant): 

Peripheral nerve injuries (PNI) affect millions of people worldwide each year. The market for therapies to treat PNI is approximately 1.3 billion dollars, and of this amount, 40% comprise nerve conduits. Nerve conduits are used to bridge the gap between severed nerves and provide a tunnel to guide regrowing neurons. But although multiple types of conduits have been developed, which ones are better at PNI repair is still a matter of debate, as few side-by-side comparisons have been done. Furthermore, all conduits are, at their most basic level, passive devices for neurons to pass through. This has led to efforts to produce conduits infused with various growth factors (e.g. BDNF) to better mimic the normal environmental milieu. However, growth factors are quite labile and easily destroyed, limiting their usefulness in vivo. Moreover, how much growth factor should be delivered is also unclear, as too much growth factor can lead to neuronal apoptosis. There is therefore a fundamental need for new proteins that can promote regeneration to circumvent these limitations. We recently discovered that delta protocadherins are essential for promoting regeneration in mice. As these are adhesion molecules, they fall into a completely different class of molecules from the commonly used family of growth factors. We argue they represent a new market opportunity to augment and enhance the utility of conduits. The goals of this proposal are: 1) partner with iFyber to compare and contrast different existing conduit platforms, 2) determine optimal conditions for infusing conduits with delta protocadherin proteins, and 3) assess the impact of various matrices infused with delta protocadherins in vivo. These studies promise to introduce a completely new family of genes into the PNI market space that can leverage the well-established use of conduits in the global market.