Phage-based targeted neural stimulation in neurodegenerative diseases – NEUROPHAGE

With more than 10 million people affected worldwide, Parkinson’s Disease (PD) is one of the most common neurodegenerative diseases with major psychological, social and economic impacts. PD is characterized by the progressive degeneration of the nigrostriatal dopamine (DA) pathway that innervates dopaminoceptive neurons of the dorsal striatum in the basal ganglia network. This results in the disconnection of the D1 dopaminoceptive neurons of the “direct pathway” in the dorsal striatum that physiologically facilitates the initiation of voluntary movements, resulting in akinesia. The current pharmacological approaches control the symptoms in the early phase, but still suffer from some long-term complications and drug-resistance issues, while alternative methods (deep brain stimulation, optogenetics) present high levels of invasiveness.
The NANOPHAGE project brings together expertise from seven research institutes across six different countries to tackle the development of innovative therapeutic strategies for PD. Here we propose the use of M13 engineered phages as nanocarriers for the specific targeting and activation of D1-dopaminoceptive neurons in the striatum. Phages will be conjugated to polymeric nanoparticles able to modulate neural activity upon light or ultrasound stimulation. With the proven capability of phage system to efficiently cross the blood brain barrier and by tuning the NPs properties to adsorb light in the near infrared, our method holds a great promise for an effective, cell-specific, minimally invasive strategy to drive activation of the direct pathway in vivo and rescue PD symptoms. This project will pave the way for a very flexible platform based on novel hybrid bio-nano interfaces applicable in vivo to rescue neural functions that are lost in neurodegenerative diseases.