Stuart Campbell, clinical sales development manager of the neurological products division at global engineering company Renishaw, discusses a new drug-delivery system for the administration of therapeutic agents directly into the brain.
There are over 600 neurological disorders, each presenting with different symptoms and affecting different parts of the central nervous system (CNS). In neurodegenerative diseases, such as Alzheimer's and Parkinson's, nerve cells become damaged or die. Globally, there are around 20 million patients with Parkinson's disease, and numbers are forecast to increase. There are currently only symptomatic treatments for Parkinson's - there is no cure.
Thankfully, advancing technology continues to ensure that medical treatments become more precise and accurate, and that our understanding of the human brain is ever more detailed.
One challenge is developing treatments that bypass the blood-brain barrier (BBB). This is the way the body filters which circulating agents in the blood can reach the CNS in order to prevent infection or disrupted brain function.
The BBB protects the brain from infections from the outside world, but creates a challenge for drug administration. If drugs are administered orally or intravenously, they are usually given in large doses to ensure some drug reaches the brain. However, as this is not really targeted, it can potentially have unwanted side effects especially in young children.
In the treatment of neurological diseases, research has focused on special delivery methods, such as injecting drugs directly into the brain to circumvent the BBB and ensure that the correct volume is delivered to the right target area.
In collaboration with consultant neurosurgeon Professor Steven Gill, Renishaw has developed a range of investigational, novel drug-delivery systems for the delivery of therapeutics into the brain. The low dead-volume, four-catheter chronic device has a cutting-edge transcutaneous port (similar to a bone-anchored hearing aid) that allows intermittent drug delivery at any time interval.
Catheters that are stereotactically delivered using the Renishaw neuromate robot are attached to a single multichannel manifold. A single multilumen tube containing the four separate infusion lines tracks back to a low-volume, skull-mounted, percutaneous port. A single-use application set for the administration of therapeutics is used to connect to the docking port and consists of a four-channel kinematic location and locking device, with each channel having an in-line air and bacteriological filter, and low dead-volume septum-piercing needle. The application set with kinematic and locking device is easily secured to the percutaneous port where re-access of the individual internal lines is achieved via a controlled advancement of four needles through the silicone septum of the port.
The complex structure of the transcutaneous bone-anchored port is produced in titanium 6Al-4V on a Renishaw AM250 additive-manufacturing system, with additional features formed through traditional subtractive machining. Secondary computer numerically controlled (CNC) machining is used for small, intricate features, such as the internal drug channels, which require extreme precision.
The surgical route is planned using a patient's MRI data and neuroinspire surgical-planning software. The catheters are then implanted submillimetrically to the planned target using the neuromate surgical robot along with the bone-anchored port.
The investigational devices have already been used to treat patients with brain tumours under humanitarian use and in a clinician-led study to treat patients with Parkinson's disease. Most recently, it was announced that Renishaw's drug-delivery system will be used in the upcoming Herantis Pharma cerebral dopamine neurotrophic factor (CDNF) Phase 1-2 clinical trial supported by a €6-million grant from the EU's Horizon 2020 Framework Programme.
Understanding has come very far, but there is still a long way to go. New drug candidates can be trialled in combination with the novel system in order to develop treatments for neurological disorders, bringing researchers one step closer to finding a cure.