Intranasal gene delivery for treating Parkinson's disease: overcoming the blood-brain barrier.
BACKGROUND
Developing a disease-modifying gene therapy for Parkinson's disease (PD) has been a high priority for over a decade. However, due to the inability of large biomolecules to cross the blood-brain barrier (BBB), the only means of delivery to the brain has been intracerebral infusion. Intranasal administration offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors, and the genes encoding them, directly to the brain.


METHODS
This review summarizes: i) evidence demonstrating intranasal delivery to the brain of a number of biomolecules having therapeutic potential for various CNS disorders; and ii) evidence demonstrating neuroprotective efficacy of a subset of biomolecules specifically for PD. The intersection of these two spheres represents the area of opportunity for development of new intranasal gene therapies for PD. To that end, our laboratory showed that intranasal administration of glial cell line-derived neurotrophic factor (GDNF), or plasmid DNA nanoparticles encoding GDNF, provides neuroprotection in a rat model of PD, and that the cells transfected by the nanoparticle vector are likely to be pericytes.


CONCLUSIONS
A number of genes encoding neurotrophic factors have therapeutic potential for PD, but few have been tested by the intranasal route and shown to be neuroprotective in a model of PD. Intranasal delivery provides a largely unexplored, promising approach for development of a non-invasive gene therapy for PD.
a 1 Northeastern University, School of Pharmacy, Bouvé College of Health Sciences, Department of Pharmaceutical Sciences , Boston, MA 02115, USA.
Amirah E-E
AE
Aly
b 2 Northeastern University, School of Pharmacy, Bouvé College of Health Sciences, Department of Pharmaceutical Sciences , Boston, MA 02115, USA +1 617 373 3312 ; +1 617 373 8886 ; b.waszczak@neu.ed.
Barbara L
BL
Waszczak
D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage; D006801:Humans; D051101:Neurturin / Q000008:administration & dosage; D010300:Parkinson Disease / Q000188:drug therapy*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D051101:Neurturin; D004364:Pharmaceutical Preparations
DNA nanoparticles; Parkinson’s disease; gene therapy; glial cell line-derived neurotrophic factor; intranasal delivery; pericytes