Affiliations: LAGENBIO. Zaragoza University, Zaragoza, Spain | Unité d'Embryologie Moléculaire, Centre
National de la Recherche Scientifique (CNRS), URA 2578, Institut Pasteur,
Paris, France
Note: [] Corresponding author: Dr. Rosario Osta Pinzolas, Lagenbio-Ingen,
University of Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain. Tel.: +34
976 76 16 20; Fax: +34 976 76 16 12; E-mail: [email protected]
Abstract: Purpose: Amyotrophic Lateral Sclerosis (ALS) is a paralyzing
disorder that kills individuals within three to five years of onset without any
possibility for effective treatment. One proposed therapy has been the use of
neurotrophic factors to inhibit the apoptosis of motorneurones. At the present,
one way to deliver neurotrophic factors after intramuscular injection to the
motor neurones is through the use of adenoviral vectors. An alternative
strategy is the use of the atoxic C fragment of tetanus toxin (TTC) as a
neurotrophic factor carrier for motorneurones. Methods: We have produced the recombinant protein fusion Glial
Derived Neurotrophic Factor and C fragment of tetanus toxin (GDNF-TTC) and we
have tested its antiapoptotic activity in degeneration culture cells and in the
symptomatic SOD^{G93A} transgenic animal model for ALS. Results: We demonstrated that GDNF-TTC induces the neuronal
survival Akt kinase pathway in mouse cortical culture neurons and~maintains its
antiapoptotic neuronal activity in Neuro2A cells. Moreover, we have found that
genetic fusion is able to increase survival by 9 days and improves life quality
in symptomatic ALS animal models. Conclusion: These results suggest that recombinant GDNF-TTC
fusion protein intramuscular injections provide a potential therapy for ALS
treatment.
Keywords: SOD1[TeX:] ^{G93A} animal model, apoptosis, survival, neurotrophic factor, neurodegenerative diseases, Amyotrophic lateral Sclerosis, fragment C of tetanus toxin
