The research team at the University of Bristol is led by Professor Steven Gill, a consultant neurosurgeon who is a world leader in the technique of convection-enhanced drug delivery and includes Mr Neil Barua, Funding Neuro’s first clinical lecturer in Neurosurgery. Professor Gill’s Functional Neurosurgery Research Group has extensive pre-clinical and clinical CED research experience and has successfully completed a number of studies which have led directly to clinical trials. This group has unique and world-leading CED catheter technology which is currently being used to treat patients with a range of neurological disorders including adults and children with malignant brain tumours and Parkinson’s Disease. However, success in this field will depend on matching the technology we have developed with effective drugs. The identification of these drugs is the major focus of our research group.

Brain stem glioma is the most common cause of cancer death in children. The majority of children with this disease are dead within 7-9 months of diagnosis. Children often experience progressive debilitating symptoms including deafness, swallowing difficulties, disordered eye movements and paralysis. The prognosis of brainstem glioma has not changed in the last 50 years and current treatment is not effective, despite advances in standard chemotherapy and radiotherapy. Often, standard chemotherapy causes intolerable side effects including hair loss, nausea and diarrhoea Clearly a new way of treating this devastating disease is required.

The aim of our research is to identify new drugs for the treatment of brainstem tumours in children using a new method of direct drug delivery into the brain. Suitable drugs are selected by undertaking a comprehensive program of pre-clinical research designed to determine whether the new drugs could be safe and effective

One of the major obstacles to the effective treatment of these tumours is the blood-brain barrier (BBB) which prevents the free passage of drugs from the bloodstream into the brain. To date, there is no evidence that any intravenous chemotherapy has shown a benefit tochildren with brainstem glioma. It is also common for children to suffer significant side-effects when chemotherapy is administered intravenously in high doses.

In Bristol the team have been treating children with aggressive brainstem tumours using a new neurosurgical method of direct drug delivery to the brain called Convection-enhanced Delivery (CED). This method involves the surgical implantation of very fine catheters into the brain using a dedicated robotic technique. They are then able to deliver drugs directly into the tumour without needing to give them intravenously. They have found this technique to be safe and to show some promising signs that is it effective. Importantly, the risk of children suffering intolerable drug side-effects when chemotherapy is administered by CED is very low.

brain and mri
Figure 1. To date the team have treated 6 paediatric patients with advanced brainstem tumours with CED of carboplatin. Using custom software they have planned and implanted up to 4 trajectories per patient in order to target the enhancing tumour and peritumoral tissue (a, blue). By performing real-time MR imaging during infusions the team obtain a measure of drug distribution (a, red). They have also developed a robot-assisted method for catheter implantation which has proved both safe and highly accurate (b). 

The team envisage progression to a phase 1 clinical trial within 2 years using world-leading and unique CED catheter technology which allows drugs to be repeatedly delivered to the brain without repeated surgical intervention. No other research group in the UK, or indeed the world, has comparable technology. We believe that if the team are successful in identifying efficacious drug combinations, when delivered using our novel catheter systems, they could make an impact on this devastating disease.

CED catheter system
Figure 2. Unique CED catheter system comprises implantable microcatheters and a skull anchored port which allows drugs to be repeatedly administered without the need for further surgery.