NOSE2BRAIN : Towards first-in-human transnasal delivery of RNAi technology to the brain (tumor) micro-environment

Glioblastoma (GBM), the most malignant brain tumor, is an invariably fatal disease with a huge ongoing medical need. Therapeutics have limited access to the tumor micro-environment due to the blood-brain barrier (BBB) and the extensive vascular tumoral shunts resulting in a poor perfusion. Using a KUL-patented technology for non-invasive, transnasal delivery of a chitosan formulated anti-Gal1 siRNA, we demonstrated shunting (rather than passing ) the BBB to selectively silence this key-hub molecule for tumor growth, invasion, angiogenesis and immune-suppression in a GBM rodent model while avoiding systemic exposure to the siRNA. Knocking down Gal1 resulted in a much stronger chemotherapy and immunotherapy effect in this model. Since relevant large animal brain tumor models are lacking and active patient collaboration, respiratory training and instruction are needed to target the deeply located olfactory mucosa in the nose, we will translate this concept to a first-in-human proof-of-concept trial in relapsed GBM patients using a TrivairTM breath-propelled nasal delivery device. This will not only transform GBM therapy but open up a new treatment paradigm for brain diseases at large.

Keywords:tumor micro-environment, Brain Diseases, Phase 0 clinical Trial, Galectin 1, chemotherapeutic synergy, Glioblastoma, small interference RNA, immunotherapeutic synergy, breath-propelled nasal delivery device, Blood Brain Barrier, strengthening IP position

Disciplines:Neurosurgery, Cancer biology, Neurosciences not elsewhere classified, Neuroanatomy, Immunomodulation therapy