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Intranasal delivery of pGDNF nanoparticles provides neuroprotection in the rat 6‐hydroxydopamine model of Parkinson's disease
Author(s) -
Harmon Brendan Trevor,
Aly Amirah,
Cooper Mark J,
Dines Karla,
Padegimas Linas,
Waszczak Barbara L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.662.12
Subject(s) - glial cell line derived neurotrophic factor , tyrosine hydroxylase , neuroprotection , parkinson's disease , neurotrophic factors , nasal administration , medicine , hydroxydopamine , substantia nigra , pharmacology , dopamine , pathology , disease , receptor
Glial cell line‐derived neurotrophic factor (GDNF) has been shown to be neuroprotective toward substantia nigra (SN) dopamine neurons in animal models of Parkinson's disease (PD) and in some clinical trials. However, its delivery to brain has required invasive surgical routes that are untenable for many patients with PD. The goal of these experiments was to test whether intranasal delivery of a GDNF expression plasmid could protect dopamine cells in the rat 6‐hydroxydopamine (6‐OHDA) model of PD. If successful, intranasal delivery of pGDNF could provide a renewable source of GDNF within the brain without need for surgical injections or frequent re‐dosing. Rats were given intranasal saline, naked pGDNF or pGDNF in a PEGylated polylysine nanoparticle (NP) preparation 7 days prior to receiving a unilateral 6‐OHDA lesion. Three weeks after 6‐ OHDA, rotational behavior to 5 mg/kg d ‐amphetamine was assessed, followed by sacrifice. Tyrosine hydroxylase (TH) immunohistochemistry revealed a significant reduction in lesion severity in the SN of rats given intranasal pGDNF NPs versus those given naked pGDNF or saline. In addition, rotational behavior was reduced in rats treated with pGDNF NPs. These results demonstrate the utility of intranasal delivery of pGDNF NPs as a non‐invasive means of gene therapy for PD and possibly other diseases of the brain. Support provided by: 2011–12 Northeastern University Tier 1 Seed Grant and the M.J. Fox Foundation.