Project overview
Traumatic spinal cord injury has long-lasting effects in patients as there are no cures to date, leaving patients without sensation and motor function below the level of the injury. The nerve cells within the brain and spinal cord are not equipped to regrow after injury due to a loss of growth-promoting molecules together with a hostile environment resulting from the injury. This inhibitory environment consists of molecules which actively block growth, including a group of molecules known as chondroitin sulphate proteoglycans, or CSPGs. Years of research in spinal cord injury using an enzyme to degrade CSPGs have shown efficacy in inducing the regrowth of damaged nerve fibres. Creating a growth-permissive environment is not the only requirement for repair. The nerve cells must also be equipped with molecules to allow them to actively grow. Previous research by my group and colleagues has identified a key growth-promoting molecule, known as alpha9 integrin, that when expressed by a damaged nerve cell, allows rigorous regrowth. However, CSPGs can inactivate the integrin molecule, reducing it's growth-promoting properties. Each treatment on its own has shown axon regeneration capabilities. This project therefore will look at the combinatorial effects of these treatments applied together.
In the current study, we will examine whether the enzyme against CSPGs known as chondroitinase ABC, can be used to create a growth-permissive environment and maintain a growth-permissive nerve cell. We propose to use our key growth-promoting molecule, alpha9 integrin, together with the chondroitinase ABC enzyme to induce a growth-promoting environment together with a nerve cell capable of regrowth. We will use both in vitro tissue culture models as well as in vivo models of spinal cord injury to test these aims.
Due to the years of promising regenerative growth observed with the use of the chondroitinase enzyme, it is nearly ready for clinical trials on spinal cord patients. It would be worthwhile to the paralysis community however to better understand the vast potential of this treatment o maximise its potential in regenerative medicine.
In the current study, we will examine whether the enzyme against CSPGs known as chondroitinase ABC, can be used to create a growth-permissive environment and maintain a growth-permissive nerve cell. We propose to use our key growth-promoting molecule, alpha9 integrin, together with the chondroitinase ABC enzyme to induce a growth-promoting environment together with a nerve cell capable of regrowth. We will use both in vitro tissue culture models as well as in vivo models of spinal cord injury to test these aims.
Due to the years of promising regenerative growth observed with the use of the chondroitinase enzyme, it is nearly ready for clinical trials on spinal cord patients. It would be worthwhile to the paralysis community however to better understand the vast potential of this treatment o maximise its potential in regenerative medicine.
