Breaching the BBB to deliver therapies into the CNS

We investigated novel approaches to deliver recombinant GCase (rGCase) into the brain using lipid nanoparticles (LNPs). These LNPs were composed of a mixture of negative, positive, and zwitterion phospholipids and were delivered intranasally into the brains of mice. A quantitative analysis performed intranasally in mice revealed a dramatic accumulation of the enzyme that was formulated into the LNPs in the brains of the mice (3.91% ± 0.3% injected dose (ID)/mg tissue)) versus the free enzyme (0.29% ± 0.07, % ID/mg tissue). The administrated particle-delivered enzymes were able to enter the brain parenchyma and accumulate in the CD11b+ cells, which are the target cells in GD. When supplied to GD-derived skin fibroblasts, a 35% ± 1.2 increase in intracellular GCase activity was measured only with the LNP encapsulated enzyme. This strategy may pave the way for novel therapeutic modalities to treat GD and other diseases such as Alzheimer’s and Parkinson’s.

  1. Goldsmith M, et al (2018) Quantitative analysis of recombinant glucocerebrosidase brain delivery via lipid nanoparticles. Nano Futures 2(4).