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

作者：Moreno Igoa Maria; Cristina Calvo Ana; Ciriza Jesus; Jesus Munoz Maria; Zaragoza Pilar; Osta Rosario^*

来源：Restorative Neurology and Neuroscience, 2012, 30(1): 69-80.

• Amyotrophic lateral sclerosis (ALS)
• Glial-cell line derived neurotrophic factor (GDNF)
• C-fragment tetanus toxin (TTC)
• neuronal apoptosis
• SODG93A mouse model

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2012