| First Author | Sábado J | Year | 2015 |
| Journal | Neuroscience | Volume | 310 |
| Pages | 38-50 | PubMed ID | 26384962 |
| Mgi Jnum | J:227496 | Mgi Id | MGI:5700595 |
| Doi | 10.1016/j.neuroscience.2015.09.027 | Citation | Sabado J, et al. (2015) Adverse effects of a SOD1-peptide immunotherapy on SOD1 G93A mouse slow model of amyotrophic lateral sclerosis. Neuroscience 310:38-50 |
| abstractText | Previous reports from our lab had shown that some anti-purinergic receptor P2X4 antibodies cross-reacted with misfolded forms of mutant Cu/Zn superoxide dismutase 1 (SOD1), linked to amyotrophic lateral sclerosis (ALS). Cross-reactivity could be caused by the abnormal exposure of an epitope located in the inner hydrophobic region of SOD1 that shared structural homology with the P2X4-immunizing peptide. We had previously raised antibodies against human SOD1 epitope mimicked by the P2X4 immunizing peptide. One of these antibodies, called AJ10, was able to recognize mutant/misfolded forms of ALS-linked mutant SOD1. Here, we used the AJ10 antigen as a vaccine to target neurotoxic species of mutant SOD1 in a slow mouse model of ALS. However, the obtained results showed no improvement in life span, disease onset or weight loss in treated animals; we observed an increased microglial neuroinflammatory response and high amounts of misfolded SOD1 accumulated within spinal cord neurons after AJ10 immunization. An increase of immunoglobulin G deposits was also found due to the treatment. Finally, a significantly worse clinical evolution was displayed by an impairment on motor function as a consequence of AJ10 peptide immunization. |
