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Restor Neurol Neurosci. 2012;30(1):69-80. doi: 10.3233/RNN-2011-0621.

Non-viral gene delivery of the GDNF, either alone or fused to the C-fragment of tetanus toxin protein, prolongs survival in a mouse ALS model.

Author information

1
Laboratorio de Genética Bioquímica, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.

Abstract

PURPOSE AND BACKGROUND:

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease with no effective therapy. Glial-cell line derived neurotrophic factor (GDNF) has been translated to clinical trials for treatment of ALS and its selective delivery to the motoneurons could improve its therapeutic abilities.

METHODS:

To test this idea, we genetically fused GDNF to the C-fragment of tetanus toxin (TTC), a peptide able to specifically deliver molecules to motoneurons.

RESULTS:

Single intramuscular administration of naked-DNA encoding GDNF or GDNF-TTC significantly delayed the onset of symptoms and functional deficits into the SODG93A mouse model of ALS, prolonging their lifespan.

CONCLUSIONS:

We have demonstrated a neuroprotective effect of GDNF-TTC as shown by the activation of survival pathways and inhibition of apoptotic proteins, such as Akt phosphorylation, or reduced caspase-3 activation respectively. However, the GDNF fusion with TTC did not improve the therapeutic effects when compared to GDNF alone.

PMID:
22124037
DOI:
10.3233/RNN-2011-0621
[Indexed for MEDLINE]

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