NanoPANS Consortium Awarded Funding for Parkinson’s Treatment
A Revolutionary Project to Combat Parkinson's Disease Using Smart Nanocarriers and Two-Photon Imaging
A pioneering research project aimed at developing innovative treatments and diagnostic tools for Parkinson's disease has received 20 000 000 DKK funding from LundbeckFonden. This ambitious initiative, "NanoPANS," focuses on creating targeted drug delivery systems to the brain. Parkinson’s Disease is driven by toxic aggregates of α-synuclein protein that damage brain cells. NanoPANS will use specially designed antibodies to neutralise these toxic protein aggregates. A key challenge for treating brain diseases is the blood-brain barrier (BBB), a protective shield that surrounds the brain, preventing harmful substances from entering. The BBB is a tightly guarded border, meticulously controlling which molecules can pass through. The NanoPANS team will utilise "smart nanocarriers," microscopic delivery vessels equipped with special keys to unlock this barrier and deliver their therapeutic cargo directly to affected brain cells.
NanoPANS will employ two innovative approaches to overcome the BBB. Prof. Martin Lauritzen explains: “Think of these nanocarriers as tiny delivery vehicles designed to transport medicine (antibodies) directly to the brain, crossing a heavily guarded BBB. This barrier protects the brain but also makes it hard for treatments to get through. These nanocarriers aim to target specific problem areas in the brain affected by Parkinson's disease, clearing out harmful proteins. There are two modalities being developed to achieve this. The first works like a taxi service: the antibodies are equipped with special ‘passes’ (called shuttles) that latch onto specific entry points on the BBB, much like a taxi docking at a station to let passengers through. These entry points mediated by transferrin receptor (TfR) and CD98hc transporter, allow the antibody to cross into the brain. The second method is more like sending packages in protective containers. The antibodies are packed into tiny ‘bubbles’ made of fat (called lipid nanoparticles or LNPs), which are coated with similar shuttles to guide them to the brain. Once they arrive and cross the BBB, the bubbles burst open, releasing the treatment exactly where it's needed.”
Here, at the Department of Neuroscience, the NanoPANS project will utilize an unprecedented approach using two-photon microscopy, a revolutionary imaging technique that allows scientists to observe the smart nanocarriers in action within the living brain. This technique allows a direct and real-time insights into the drug delivery process. Assoc Prof. Krzysztof Kucharz, highlights the significance of this approach: "Two-photon imaging is the technique for the job due to its superior spatial and temporal resolution in vivo. By employing two-photon microscopy, we aim to understand the exact mechanisms of how the smart nanocarriers cross the BBB and how they are transported within the brain. Two-photon imaging has key advantages over standard techniques typically used to assess pharmacokinetics and pharmacodynamics in vivo, e.g. microdialysis, MRI etc. It allows us to open the black-box of the BBB and trace, quantify and understand all steps of delivery of nanocarriers to the brain, from the moment to injection, passage via BBB, to interaction with therapeutic targets”. This knowledge is crucial for optimising the design of these delivery systems and ensuring they reach their target with maximum efficacy.
The NanoPANS project is a collaboration between leading scientists in nanotechnology, neurobiology, and imaging. It involves Professor Daniel Otzen (Aarhus University), Professor Nikos Hatzakis, Associate Professor Céline Galvagnion, Professor Martin Lauritzen, and Associate Professor Krzysztof Kucharz (University of Copenhagen). It marks a major advancement in combating Parkinson's disease and offers substantial potential for creating nanocarrier-based therapies for other neurological disorders, e.g., Alzheimer’s disease. If successfully developed, this technology could transform neurological treatment, providing safer and more effective therapeutic options.