Neural/Glial Cell-Derived Nanoparticles to Restore Neural Function in Alzheimer’s Disease

This invention is an engineered biomimetic nanoparticle (NP) that integrates neural or glial cell membrane proteins into lipid-based nanoparticles (a.k.a. neurosomes). The integration of these neural/glial cell proteins within the NP shell enable precise targeting to treat a variety of neurological disorders resulting from trauma, neurodegeneration, and/or neuroinflammation. Our current focus relies on using these NPs to achieve targeted delivery of anti-inflammatory agents to  inflamed astrocytes as a treatment stategy for Alzheimer’s disease, although we are also investigating the use of these NPs in other neurological indications.

 

Stage of Development

 

In vitro data: We have developed and validated two neurosome formulations (one for chemical compounds and one for genetic cargo), both of which display increased co-localization and uptake in neural cells compared to liposomes. Additionally, cytotoxicity assays revealed that neither neurosome formulation produced neurotoxicity at concentrations of 100uM in 2D cell cultures and 500uM in 3D cell cultures.

 

Competitive Landscape

 

Restoration of neural function after trauma, neurodegeneration, and neuroinflammation is currently hindered by a lack of effective and clinically applicable biotechnologies for cell-targeted therapy. Enabling technologies are urgently needed to improve sustained delivery of therapeutic cargo (e.g. genetic and chemical compounds) and avoiding potential side effects that may occur with viral delivery. Bio-inspired tools such as exosomes have demonstrated tremendous promise in this area, however, the complexity and variability of cellular sources reduces their potential for scalable use in the clinic. Functionalized NPs with various surface modifications, such as coupling peptides or antibodies to NPs or modifying surface charge for selective neuron-specific targeting, have been employed to increase targeting efficacy. Alternatively, exosome-like lipid NPs have also been used for delivery to the brain as a means to mimic neural cellular communication. Unfortunately, standardized protocols for storage and characterization of these NPs have not yet been fully established and low yield from biological sources reduces the potential of translating these therapeutic strategies into the clinic.

 

Competitive Advantages

 

•       Enhanced neural or glial cell targeting

•       Off-the-shelf potential 

•       High-yield, scalable, reproducible, rapid, and cost-effective manufacturing process

 

Patent Information:
Licensing Contact
Michael Cato
mcato@houstonmethodist.org

Inventors:
Robert Krencik
Assaf Zinger
Ennio Tasciotti
Caroline Cvetkovic