A Spinal Research project which is developing the enzyme chondroitinase for use in clinical trials to repair the injured spinal cord is reporting some excellent results.
Following spinal cord injury (SCI), nerve cells fail to regenerate, resulting in permanent paralysis. This is due in part to the presence of molecules in the injury zone that are inhibitory to nerve regrowth. Chondroitinase is a bacterial enzyme which removes these inhibitory molecules and also appears to reactivate the ability of intact nerve fibres to sprout new growths (‘plasticity’), enabling them to make new connections and take over the functions of the damaged nerve cells; it has also been shown to promote nerve cell survival. These multiple properties of the enzyme make it a very promising candidate for the treatment of human SCI.
However, it is likely that repeated injections over several weeks would be required for treatment carrying the risk of causing further trauma and also of triggering an immune reaction in the patient.
Our project based at the University of Cambridge under the supervision of Dr Liz Muir has the aim of developing a form of deliverable chondroitinase which is safe and effective for use in clinical trials with injured patients.
In a Spinal Research-funded collaboration with Dr Liz Bradbury (King’s College London) the team have tested the delivery of the enzyme via viral vectors (particular types of controlled viruses) and they have shown that viral delivery of the gene that creates the enzyme has resulted in the most extensive removal of inhibitory molecules around the site of SCI seen to date.
They also found that active enzyme was still present eight weeks after a single injection (doing away with the need for multiple injections) and that the enzyme delivered by this method does not damage tissue.
In addition, when the virus is injected into the site of injury, it prevents much of the secondary tissue damage that normally ensues, resulting in the sparing of many nerve cells, dramatically improved nerve function, and significant improvements in behavioural function.
These results show that this method of delivery, carrying the dual advantage of safety and longevity, is suitable for further development and use in patients.
The team are now collaborating with numerous laboratories around the world to futher develop this therapy with promising results.