Phage-based targeted neural stimulation in neurodegenerative diseases

Parkinson’s Disease (PD) is one of the most common neurodegenerative diseases and is characterized by the death of the midbrain dopamine neurons of the substantia nigra, projecting to the dorsal striatum.

In the striatum, the loss of dopamine input reduces the activity of the neurons of the “direct pathway”, which plays a key role in the initiation of voluntary movements. This in turn results in the cardinal motor symptoms of PD, such as rigidity and akinesia.

Current therapies for PD control the symptoms in the early phase of the disease, but suffer from 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 from six countries to develop innovative therapeutic strategies for PD.

We propose the use of M13 engineered phages as nanocarriers to target and activate the striatal dopaminoceptive neurons of the direct pathway.

Phages will be conjugated to polymeric nanoparticles able to modulate neural activity upon light or ultrasound stimulation.

With the proven capability of the phage system to efficiently cross the blood brain barrier and by tuning the nanoparticles 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 efficiently counteract PD symptoms.