RNS60 exerts therapeutic effects in the SOD1 ALS mouse model through protective glia and peripheral nerve rescue

• DOI: 10.1186/s12974-018-1101-0
• Publication Date: 2018-03-01T13:21:16Z
• Authors: Antonio Vallarola; Francesca Sironi; Massimo Tortarolo; Noemi Gatto; Roberta De Gioia; Laura Pasetto; Massimiliano De P...; Alessandro Mariani; Supurna Ghosh; Richard Watson; Andreas Kalmes; Valentina Bonetto; Caterina Bendotti
• Keywords: Astrogliosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects the motor neuromuscular system leading to complete paralysis and premature death. The multifactorial nature of ALS involves both cell-autonomous non-cell-autonomous processes contributes lack effective therapies, usually targeted single pathogenic mechanism. RNS60, an experimental drug containing oxygenated nanobubbles generated by modified Taylor-Couette-Poiseuille flow with elevated oxygen pressure, has shown anti-inflammatory neuroprotective properties in different paradigms. Since RNS60 interferes multiple cellular mechanisms known be involved pathology, we evaluated its effect vitro vivo models ALS.Co-cultures primary microglia/spinal neurons exposed LPS astrocytes/spinal from SOD1G93A mice were used examine or normal saline (NS) on selective neuron degeneration. Transgenic treated NS (300 μl/mouse intraperitoneally every other day) starting at onset examined for progression as well pathological biochemical alterations.RNS60 protected paradigms slowed C57BL/6-SOD1G93A through significant protection spinal junctions. This was mediated (i) activation antioxidant response generation environment cord; (ii) PI3K-Akt pro-survival pathway cord sciatic nerves; (iii) reduced demyelination (iv) elevation peripheral CD4+/Foxp3+ T regulatory cell numbers. did not show same effects 129Sv-SOD1G93A mice, which are unable activate protective immune response.RNS60 demonstrated therapeutic efficacy virtue neurons, glial cells, cells. These findings, together excellent clinical safety profile, make promising candidate therapy support further studies unravel molecular mechanism action. In addition, differences strains may relevant identifying potential markers predict trials.