Chondroitinase a.k.a. CH’ASE spinal cord injury recovery treatment research
Chondroitinase gene therapy research project for chronic spinal cord injury repair
Background information: The application of a bacterial enzyme called Chondroitinase, or Ch’ase, has repeatedly been proven to degrade the scar, to promote growth and to improve recovery in animal experiments. However, applying it to people is challenging. The goal of the project “CHASE-IT”, initiated by the International Spinal Research Trust (ISRT), is to make the Ch’ase therapy ready and safe for clinical application. It relies on an international collaboration between various researchers, among others in the UK and in The Netherlands. Recent experiments, using gene therapy models to deliver the enzyme, have moved the therapy closer to human application.
Latest update and results so far (May 2020): Two alternative gene delivery therapies (the gene for Ch’ase is expressed in an active form in human cells and can be switched on and off to ensure an optimal and controlled delivery) have been developed/ are being tested:
a- The chondroitinase enzyme is delivered via a Lenti-virus vector (a virus made harmless and capable of carrying therapeutic genes). The consortium demonstrated this exciting new approach gave rise to improved walking and unprecedented upper limb function in rodent acute spinal cord injury models. See more information in this article and video and this Brain publication (August 2018). The same treatment was tested in a rodent chronic injury model at the end of 2018. The latest chronic trial has only shown modest results in terms of recovery and the current focus of the researchers is to combine treatment with rehabilitation to improve. More work has yet to be carried out to obtain the expected functional efficacy.
b- The Ch’ase enzyme is delivered via an Adeno-associated viral (AAV) vector which has the advantage of already being used in other human treatments and would, therefore, allow easier access to clinical trials. Various AAV vectors were created by Verhaagen’s lab and tested but they need further adjustment to ensure that the vector can be totally switched off when needed, without any further leakage. Indeed, one issue researchers found with AAV vectors was a noticeable background expression of the chondroitinase in the “off” setting.