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


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.


CONCLUSIONS
The findings may have implications for long-term non-invasive gene therapy for neurodegenerative diseases in general.
Huang
Rongqin
R
Department of Pharmaceutics, Fudan University, Shanghai 201203, China.
Ke
Weilun
W
Liu
Yang
Y
Wu
Dongdong
D
Feng
Linyin
L
Jiang
Chen
C
Pei
Yuanying
Y
D000818:Animals; D002908:Chronic Disease / Q000628:therapy; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000627:therapeutic use; D049452:Green Fluorescent Proteins / Q000235:genetics; D007781:Lactoferrin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D053758:Nanoparticles / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity; D016896:Treatment Outcome; D014475:Uncoupling Agents / Q000633:toxicity
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009498:Neurotoxins; D014475:Uncoupling Agents; D012402:Rotenone; D049452:Green Fluorescent Proteins; D007781:Lactoferrin