The future of chronic spinal cord injury repair – a focus on chondroitinase for clinical trial

fighting paralysis…and winning

Wednesday 7th November 2012
King’s College London

At Spinal Research our aim is to find an effective treatment for spinal cord injury that not only improves sensation and movement for people living with paralysis, but brings us closer to a day when we finally conquer it. Thirty years ago spinal cord injury was considered incurable and few people, if any, were contemplating research into repair. Today we are standing on the brink of clinical trials of therapies that will restore movement and feeling and transform the lives of paralysed people. Significant successes in our research mean that we have identified chondroitinase as a treatment, proven in the laboratory, with the potential to prevent or reverse paralysis following a spinal injury.

Chondroitinase is a bacterial enzyme which is able to digest the scar tissue that impedes nerve regeneration and stifles changes needed for effective rehabilitation. We are currently looking to modify this enzyme into a form that is safe for use in humans. This will be a significant step forward and will open the way to clinical trials using this treatment. Our experience of chondroitinase illustrates there is a window of opportunity to enhance beneficial plasticity; a time when new connections can be made and function recovered. At a fundamental level, enhancing plasticity may also offer therapeutic opportunities in other neurological disorders such as stroke, traumatic brain injury, blindness and even impaired memory to name a few. A key priority for the future is to bring the first plasticity treatment to the clinic.

The following research projects involving chondroitinase are currently being funded by Spinal Research:
Development of the enzyme chondroitinase for use in clinical trials with spinal cord injury.
Dr Elizabeth Muir, Professor Roger Keynes and Professor James Fawcett, Cambridge Centre for Brain Repair, UK The aim of this project is to modify the chondroitinase enzyme into a form that is safe for use in humans so that it can be taken into clinical trials. So far this project has produced fantastic results which have already exceeded our initial expectations. The team has shown that treated animal models have reduced scarring, preserved nerve function in the injury zone and demonstrated better recovery of normal movements. These results indicate that this new method for the treatment of spinal cord injury holds great promise, and has generated much excitement in the scientific community. The next stage is to drive this research forward and take chondroitinase to clinical trials.

Chondroitinase Steering Group As a result of the success of the Muir and Fawcett project, Spinal Research is now entering a clinical development phase for this exciting therapeutic concept. It has brought together six leading figures in the field of chondroitinase research to formulate a detailed development plan outlining the essential criteria and milestones this new treatment must achieve in order to enter a ‘first in man’ study. The team will establish the target patient group, the best course of development, the most effective method of delivery and the quickest route to clinical trials. They will also look at budget requirements and how to sustain this ambitious programme through to safe application to those living with a spinal cord injury.

The steering group will include:

· Dr Elizabeth Bradbury – Kings College, London.
· Professor Jerry Silver – Case Western Reserve University, USA.
Dr Silver’s team have recently shown an 80-90% restoration of
breathing in the laboratory using chondroitinase.
· Professor James Fawcett – University of Cambridge, Centre for
Brain Repair. Professor Fawcett was part of the team which first
developed chondroitinase.
· Dr Liz Muir – University of Cambridge.
· Dr Joost Verhaagen – Netherlands Institute for Neuroscience,
Netherlands. The team will use the viral vectors developed by Dr
Verhaagen.
· Professor Armin Curt – University Hospital Balgrist, Zurich.
Professor Curt is a leading scientist in Europe and will help to lay
the path for clinical trials.
· Dr James Guest – Miami Project to Cure Paralysis, USA. Dr Guest
has previous experience of applying for and conducting clinical trials
in America.
· Dr Mark Bacon – Director of Research, Spinal Research.

Nathalie Rose Barr Studentships
To sustain the future of our research into spinal cord repair, we encourage the development of talented, highly-motivated young scientists in both clinical and basic science research. The following projects involve chondroitinase:
Maximising recovery of function after spinal cord injury with a combination of electrical stimulation and chondroitinase
Dr Ronaldo Ichiyama, University of Leeds
The project is looking at the effects of epidural electrical stimulation combined with the delivery of chondroitinase. Epidural stimulation has already been shown to promote locomotor function, and chondroitinase is widely recognised as one of the most promising therapies for spinal cord repair.
Dr Ronaldo Ichiyama
His team will test the optimum timing and method of delivery for this type of combined treatment, which is a precursor to successful universal treatments for people living with paralysis – both for the newly injured and those living with longer-term spinal cord injury. Combinatorial treatment to regulate scar formation and promote regeneration in spinal cord injury.
Professor Arthur Butt, University of Portsmouth, in collaboration with Dr Elizabeth Bradbury This project involves two of the leading experts in their fields. Dr Bradbury’s work has already shown that treatment with the enzyme chondroitinase ABC (ChABC) promotes axon regeneration and partial recovery following spinal cord injury in an animal model. Professor Butt has shown that another enzyme called glycogen synthase kinase (GSK3β) triggers profound changes in cellular composition and that inhibiting production of GSK3β stimulates axon regeneration in spinal cord injury. This project will therefore look at the effects of GSK3β inhibition on scar formation and axon regeneration following spinal cord injury, both singly and in combination with ChABC. It is predicted that combined treatments will promote targeted regeneration to a greater extent than single treatments. It is important to determine the effectiveness of combinatorial strategies in maximising the extent of repair, with the ultimate aim of being able to translate these findings into treatments for spinal cord injured patients.

Visit: www.spinal-research.org

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