A novel wireless implantable device for Parkinson’s disease
Parkinson’s disease is a progressive neurodegenerative disease that currently has no cure. It affects all aspects of daily life, in particular through debilitating motor symptoms such as tremors and instability. Roughly 1.2 million people have Parkinson’s in the EU alone, a figure expected to double by 2030. “Parkinson’s disease is caused by the degeneration of dopamine neurons that strongly innervate the basal ganglia (BG), an ensemble of brain regions that controls movements,” explains Farshad Moradi, a professor in the Department of Electrical and Computer Engineering at Aarhus University. In the EU-funded STARDUST project, Moradi’s team devised a new solution aiming to restore motor function in patients with Parkinson’s disease. STARDUST developed a new implantable device – known as Dust – that enables drug delivery for the treatment of Parkinson’s disease in a mouse model. The device uses light to activate specific proteins in the brain, a process known as optogenetics. “We propose to use optogenetic neuromodulation to normalise the motor function of the globus pallidus externalis (GPe), a nucleus in the basal ganglia with altered activity in Parkinson’s disease,” says Moradi. “To reach this area of the brain, we proposed a fully implantable device for delivering the desirable wavelength of light targeting these specific neural circuits,” adds Moradi. “The device enables optogenetics experiments in a freely moving animal, where it records data, communicates it wirelessly, and delivers drugs locally.”
Mice trials with light-responsive proteins
To assess the device’s efficiency in producing a locomotor response, the team ran a series of trials. First, they implanted ‘dummy’ devices in experimental mice to find the best way of installing it along with a transducer. Mice then received channelrhodopsin, a protein that responds to light, into their motor cortex 8-10 weeks before transplantation of prototype devices. These devices were activated during trials, though appeared to give no behavioural response in the mice. This could be due to many reasons, including insufficient light intensity for driving neuronal activation in vivo, or because the transducer and device fell out of alignment after implantation. “ Unfortunately the integration of components somehow was unsuccessful which significantly affected the in vivo studies,” he says.
Promising initial results
Nevertheless, the STARDUST project delivered several promising developments. The team developed a set of molecular optogenetic tools for excitatory or inhibitory application, and optimised the performance of channelrhodopsins within the mouse model. “By photoactivation of GPe neurons, we could alleviate a wide range of abnormal motor behaviours reminiscent of Parkinson’s symptoms in patients,” Moradi explains. “These results highlight the importance of GPe in the pathophysiology of the disease.” The researchers also developed a light-triggered drug delivery system based on polymers, which activates when exposed to UV light and deactivates when in green light.
Future development of the device
Now that the project has ended, the scientists will continue the research under different pathways. “One direction is to work further on the development of the device through calls like EIC Transition,” says Moradi. “Another is to work still on the neuroscience part of the study, to reach different regions of the brain. This will help us answer questions in neuroscience with an enabling technology, targeting regions that are unreachable through standard or existing devices.”
Keywords
STARDUST, mice, optogenetics, Parkinson’s, disease, light, sensitive, proteins