Breaking Barriers: The engineering behind a new Parkinson’s drug delivery system

Breaking Barriers: The engineering behind a new Parkinson’s drug delivery system

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The surgeons use MRI scanning images to monitor where the catheters are being placed, a process first mapped out in Renishaw’s neuroinspire surgical planning software. This software platform enables doctors to pull in MRI and CT scan data and merge them together, allowing them to assess the soft tissue within the brain and the hard tissue around the brain. From there, the surgeons can see the area they want to target, and the areas they would rather avoid, as Paul Skinner, General Manager of Renishaw’s Neurological Products Division, told TCT.

“They place CAD images of the catheters and the port into the right position for that particular patient and will plan the whole surgery within the software, so they’d put four of the catheters exactly where they want, looking at where they want to get to within the brain, but also the right path to get [there] from the outside of the skull, avoiding blood vessels and other critical structures.”

Viewing scan data through the neuroinspire software resembles a woody vine that surgeons must digitally slalom through to implant the device safely. Hitting a blood vessel is likely to result in the patient suffering a stroke.

The procedure is high-risk, but for Parkinson’s and other brain conditions, like tumours and dementia, certain therapeutics must be infused directly into the organ to have a chance of significant effect.

“The brain has a mechanism for stopping large molecules getting from the bloodstream into the brain, what is called the ‘blood-brain barrier’,” Skinner explained. “Every other organ in the body you can actually put things into the bloodstream and those molecules will cross across into those organs. But the brain stops large molecules getting in, and so it stops toxins getting [in], which is fine for normal living, but if you want to treat the brain with some therapy then you actually want to get those things from the bloodstream into the brain. If you can’t, you need to find another way of doing it.”

Through more than a decade of research and development in neuroscience, a team, utilising Renishaw technology, did. Each month, participants in the GDNF clinical trial would re-visit the hospital for their infusions, surgeons aided throughout by the neuromate robotic arm and its precise targeting capabilities. During the first nine months of the trial, half of the participants were on a placebo, the other half receiving the real thing. For the second nine months, all patients were being injected with GDNF, the doctors ruling that, ethically, it would be unfair to put the participants through brain surgery without ever receiving the GDNF treatment.

The first half of the trial wasn’t without its hiccups. One implantation of the delivery system was inaccurate and so an inadequate dose of GDNF was being delivered into the putamen. Meanwhile, there were five participants whose titanium ports had come loose. The awry implantation was down to user error and required a second operation, but the loose ports were a matter for Renishaw to fix.

“At that stage, the port was completely reliant on the bone integration to happen, so they weren’t screwed down,” Skinner said. “We introduced another part to the port which was actually screwed down to the skull and therefore it was screwed down during the period that the bone integration happened. Before, it was a press fit into the skull, so you drilled a hole and the port was actually pressed into it. What we did was we created some legs on it which were screwed down into the surface of the skull in order to keep it stable during that healing process.”

Every two months, patients underwent baseline tests to assess their progress. Placing finger on nose, turning hands, and touching points at either end of the same desk as quickly as they could. The signs were encouraging. By the time the trial was reaching its climax, some participants were able to touch pinkie finger to thumb, others could jog, one woman said she had stopped tremoring completely. In 2014, pharmaceutical giant Pfizer reached an exclusive licencing agreement with MedGenesis, the owner of GDNF, to take the drug forward. Hope was evolving into expectancy.