Global engineering technologies company, Renishaw has announced that its award-winning intraparenchymal drug delivery device, has played a critical role in a joint Phase 1-2 clinical study with Herantis Pharma plc, for the investigation of cerebral dopamine neurotrophic factor (CDNF) as a treatment for Parkinson’s disease.
Parkinson’s is a neurodegenerative disease, caused by the break-down of dopamine producing neurons in the brain. Symptoms include involuntary shaking, stiffness of muscles and slowing down of movement, which can be extremely debilitating. In addition, patients can suffer associated non-motor symptoms such as difficulty sleeping, memory loss, anxiety and depression. Whilst these symptoms can initially be managed with medication, there is currently no treatment available that effectively prevents disease progression, or that treats the motor and non-motor symptoms together.
The study’s repeated delivery regime, which allows for a prolonged therapeutic window, is crucial to achieve the potential neuroprotective and neurorestorative actions of CDNF and has been made possible through the use of Renishaw’s ground-breaking drug delivery system.
Initial results indicate predictable and accurate placement of the device as well as its positive performance and safety. The Company will continue to assess the results as the data is analysed and through the extension part of the study, as patients receive ongoing monthly infusions of CDNF using the Renishaw device.
Rupert Jones, managing director of Renishaw Medical, says, “The results of this trial and the performance of Renishaw’s drug delivery system are promising for the many people with Parkinson’s disease and I would like to take this opportunity to thank the trial participants for making this possible.”
He adds, “These results allow us to build towards CE marking of Renishaw’s device so that further neurodegenerative and neuro-oncological conditions can benefit from our technology. We see our device as an enabling technology that facilitates the reliable and repeated delivery of therapeutic agents direct to targets deep within the parenchyma, as part of a paradigm shift in the way treatments of neurological disorders and brain tumours are progressing.”
Renishaw’s intermittent drug delivery system comprises of up to four catheters, which can be implanted into target areas within the brain. The catheters are accessed via a 3D printed titanium transcutaneous port implanted behind the patient’s ear. Drug-filled infusion lines are connected using an MRI compatible application set, which repeatably locates onto the port. Retractable needles extend through a septum in the port to enable therapeutics in the external infusion lines to be infused through the implanted catheters.
Renishaw’s neuroinfuse chronic
drug delivery system is composed of up to four catheters, which are implanted into a target area within
the brain. The catheters can be accessed via a 3D printed titanium
transcutaneous port implanted behind the patient’s ear. Drug-filled infusion lines are connected using an MRI compatible, 3D printed, titanium application set, which repeatably locates onto the port. Retractable needles extend through a septum in the port to enable therapeutics in the external infusion lines to be infused through the implanted catheters. The port features a roughened surface below the skin to encourage bone integration and device anchorage, whereas above the skin, it is polished to discourage bacterial settlement.
The device holds promise for the treatment of a range of neurological conditions and brain tumours. It is currently being used in a Phase I – II clinical study with Herantis Pharma Plc, investigating cerebral dopamine neurotrophic factor (CDNF), for the treatment of Parkinson’s disease. It is also currently being used on humanitarian grounds to treat children suffering with diffuse intrinsic pontine glioma (DIPG), an aggressive form of brain tumour that occurs in a difficult to access area of the brain. DIPG most commonly affects five to ten year olds.
“There is currently no approved method for the chronic delivery of drugs for neurological disorders into the brain,” explains Dr Max Woolley, technical fellow and head of Drug Delivery Device Research and Development, at Renishaw. “This device has the potential to completely change how neurological diseases are treated. The port allows repeated delivery of pharmaceuticals over long periods of time, without the need for further surgery — patients can be admitted as outpatients for the infusions.”
“If we produced the device using traditional subtractive machining, we estimate it would have required up to ten parts,” added Woolley. “By designing for metal additive manufacturing, it was possible to produce it as one component, reducing the time needed for manufacture and the potential for error from unnecessary assembly operations.”
Thanks to this innovative, patented design, patients are able to receive infusions in an out-patient setting, rather than requiring the reimplantation of new catheters for each infusion, which has been the only option for many trials to date.
The study was a first-in-human study whereby 17 patients were randomised to receive either one dose per month for six months, of a placebo, or six increasing doses of Herantis Pharma plc’s novel drug candidate, CDNF, over the same period in a blinded manner. After this six month period, patients may enter into an additional six-month study where all participants receive CDNF. In total, patients will receive 12 infusions, all delivered in an out-patient setting.
The primary endpoints evaluate the safety, performance/tolerability of both the drug delivery system and CDNF as well as surgical accuracy. Secondary to this, the potential efficacy of the drug, rated against the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score evaluation, was also monitored.
The clinical study has received funding from the European Union’s research and innovation programme Horizon 2020.