Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model

Rongqin Huang, Weilun Ke, Yang Liu, Dongdong Wu, Linyin Feng, Chen Jiang, Yuanying Pei

Research output: Contribution to journalArticle

Abstract

Background: Gene therapy is considered one of the most promising approaches to develop an effective treatment for Parkinson's disease (PD). The existence of blood-brain barrier (BBB) significantly limits its development. In this study, lactoferrin (Lf)-modified nanoparticles (NPs) were used as a potential non-viral gene vector due to its brain-targeting and BBB-crossing ability. Methods and results: The neuroprotective effects were examined in a rotenone-induced chronic rat model of PD after treatment with NPs encapsulating human glial cell line-derived neurotrophic factor gene (hGDNF) via a regimen of multiple dosing intravenous administration. The results showed that multiple injections of Lf-modified NPs obtained higher GDNF expression and this gene expression was maintained for a longer time than the one with a single injection. Multiple dosing intravenous administration of Lf-modified NPs could significantly improve locomotor activity, reduce dopaminergic neuronal loss, and enhance monoamine neurotransmitter levels on rotenone-induced PD rats, which indicates its powerful neuroprotective effects. Conclusion: The findings may have implications for long-term non-invasive gene therapy for neurodegenerative diseases in general.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalJournal of the Neurological Sciences
Volume290
Issue number1-2
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

Keywords

  • Brain gene therapy
  • Lactoferrin-modified nanoparticles
  • Multiple dosing administration
  • Parkinson's disease
  • Rotenone

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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