Innovative UK technology that can deliver drugs deep into the brain to treat neurological diseases, from Parkinson’s to cancer, has had encouraging results in its first controlled clinical trial.
Steven Gill, professor of neurosurgery at the University of Bristol, designed the new convection enhanced delivery system to bypass the blood-brain barrier which makes it hard to target medicines inside the head. It is manufactured by Renishaw, a British precision engineering company.
The CED device uses four tubes, fitted through robot-assisted surgery, to infuse drugs in solution directly to the putamen, a structure at the base of the forebrain that plays an important role in Parkinson’s. Patients lived for many months with an entry port — that looks like a plastic plug — on the side of their head without suffering side-effects.
“This trial has shown that we can safely and repeatedly infuse drugs directly into patient’s brains over months or years,” said Prof Gill. “This is a significant breakthrough in our ability to treat neurological conditions . . . because most drugs that might work cannot cross from the blood stream into the brain due to a natural protective barrier.”
The inaugural CED trial was with 35 Parkinson’s patients at Bristol’s Southmead Hospital, who were administered an experimental drug called GDNF, which promotes the growth of brain cells. Results are reported in scientific papers in Brain and the Journal of Parkinson’s Disease.
Participants showed some clinical improvement, in particular easier movement of their limbs, compared with those who received an inactive placebo solution through the CED device. Scans also showed more regrowth of brain cells in treated patients, though the overall outcome failed to confirm that the medication had reversed the underlying condition — something that no existing treatment can do.
“Now we need to move towards a definitive clinical trial using higher doses,” Prof Gill said. Regulators in Europe and the US have agreed that a more extensive GDNF trial can go ahead, though funding still has to be arranged.
Neuroscientists who were not directly involved in the Bristol trial gave it a cautious welcome. “For a neurodegenerative condition of this complexity, I think the results are remarkably positive,” said Roger Morris, professor of molecular neurobiology at King’s College London.
They also praised the possibilities of CED. “If intra-brain perfusion can be safely achieved for long-term drug delivery inside the brain, the range of medication that can be used to combat brain diseases [stroke and cancer as well as neurodegeneration] will be massively expanded,” said Prof Morris.
Prof Gill is working with Herantis Pharma, a biotech company in Finland, on a separate Parkinson’s disease trial using the same CED delivery system to administer another experimental drug called CDNF that also promotes neural growth. It has not yet reported any results.
A third application is for a lethal childhood brain cancer called diffuse intrinsic pontine glioma, or DIPG. “This accurate targeting of the tumour has shown encouraging results in a number of children with DIPG treated on a compassionate basis,” said Sharon Kane, chief executive of the neurosurgery charity Funding Neuro. “There has been no progress in treatment for children with DIPG for almost 60 years, and we believe that CED will be the mechanism that will help to change the outcome for patients with this devastating diagnosis.”