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Prof.Liz Bradbury at Kings College London


Chondroitinase ABC for Spinal Injury Therapy

The aim of the CHASE-IT project is to develop an effective therapy for spinal cord injury using the neuroplasticity enhancing properties of the bacterial enzyme chondroitinase.

After a spinal cord injury, a scar develops which blocks the way for re-growing nerves which might otherwise be capable of making useful new connections to restore movement and function. Chondroitinase is able to modify the scar tissue and promote rewiring of the nervous system.

Scientific leads:
Professor Elizabeth Bradbury, King’s College London
Dr Elizabeth Muir, University of Cambridge
Professor Joost Verhaagen, Netherlands Institute for Neuroscience
Dr Rafael Yáñez-Muñoz, Royal Holloway University of London

The motivation to develop the CHASE-IT consortium came from the remarkable finding that chondroitinase enzyme delivered via gene therapy, leads to far better neurological outcomes than direct injection of the enzyme, particularly in contusion injuries. This was only made possible by the molecular re-engineering of chondroitinase, developed by Dr Liz Muir and colleagues at University of Cambridge who created a version of chondroitinase that could be expressed by human cells.

The challenges of developing a gene therapy treatment for spinal cord injury are considerable.

Specifically, the teams are working to reduce toxicity, remove the chance of tumour formation and contain the treatment to the target tissue.

They have chosen to focus on two different delivery systems to transport chondroitinase to the injury site in animal models of spinal cord injury. Both delivery systems are similar in concept and work in broadly the same way by making use of a virus as a vehicle to carry a therapeutic gene into cells which then go on to produce the therapeutic protein chondroitinase.

Recent studies have shown that delivering chondroitinase by gene therapy gives far better results than direct injection of the bacterial protein.  Encouraged by this, the CHASE-IT consortium was established to work on optimizing the gene therapy approach to make it clinically acceptable. Primarily this has meant the development of an effective way to turn the treatment ‘on’ and ‘off’ when used in patients as this is a key safety issue.

In November 2016 the CHASE-IT consortium team at King’s College London identified a suitable antibiotic, called doxycycline that does this. They found the different levels between the ‘on’ and ‘off’ states with this drug were extremely high, which means they could see the enzyme working and not working. This bodes well for safe clinical application as it means it’s actions can be monitored and managed effectively.

Just as exciting, they also found that long-term treatment showed, for the first time, very significant improvements in forelimb and paw function in a contusion injury. These functions are under the control of the corticospinal tract (CST) which is known to be particularly poor in its regenerative response. The CST is also known to be particularly important for motor function in humans, allowing movement of the body.

What Next?

Formal safety and toxicology studies are now needed to determine and demonstrate the safety profile. We now require funding to allow us to perform these studies before an application can be made for clinical trial.

This progress has only been possible because of our amazing supporters, who have believed in the research and generously supported it, enabling us to discover more about this very important enzyme and its effects on nerve regeneration.

History of chondroitinase
Swen in the pub

It's the simple things I miss, making my own cup of tea, cooking my own food - the way I want it, holding the knife and fork myself.

Swen on the things that matter to him

Other Translational projects

Human olfactory ensheathing cells
Human olfactory ensheathing cells

Olfactory ensheathing cells (OECs)

Olfactory ensheathing cells are cells found in the nose that can provide new cellular pathways down which nerves can grow to make new connections. Isolating and culturing the human form of olfactory ensheathing cells have already proved effective in enabling nerve re-growth after spinal cord injury in animals.

Professor Adina Micheal-Titus
Professor Adina Michael-Titus

Fish Oils

An early intervention treatment using poli-unsaturated fatty acids (PUFAs) which can be applied immediately after a spinal injury to limit damage. At Queen Mary, University of London, Professor Adina Michael-Titus reports that the PUFA solution which is being developed for clinical use appears to be stable and is well tolerated, so it seems feasible to concentrate and stabilise these fatty acids for use in emergency situations.

The Facts

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people every day are told they will never walk again
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People in the UK and Ireland are living with paralysis caused by spinal cord injury
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2.5 million

people worldwide live with paralysis caused by spinal cord injury

Research is possible but we need you

Help us fund the next stage of research in this potentially life-changing treatment.