Microglial Activation Role In ALS (MARIA)

Summary

Neuroinflammation, characterized in particular by microglia activation, is an essential component of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Translocator Protein (TSPO) is recognized as a specific and sensitive biomarker of neuroinflammation, reflecting disease activity. An experimental radiopharmaceutical specific of TSPO expression, namely \[18F\]DPA714, allow to quantify this microglial activation using Positon Emission Tomography (PET) imaging. The purpose of this study is to longitudinally correlate the spatial distribution of neuroinflammation with the pro- or anti-inflammatory state of activated microglia cells in ALS, in order to evaluate neurotoxic or neuroprotective microglia activity, by complementary approaches in 20 ALS patients: * in vitro: measuring concentrations of several pro- and anti-inflammatory cytokines secreted by microglial cells in the cerebrospinal fluid (CSF). * in vivo: \[18F\]DPA714 PET imaging. These assays will be performed in the framework of the clinical follow-up of ALS patients, at the diagnosis of ALS disease and 6 months latter.

Timeline

Start

2015-03

Primary completion

2016-09

Completion

2017-03

Publications

• Results Corcia P, Valdmanis P, Millecamps S, Lionnet C, Blasco H, Mouzat K, Daoud H, Belzil V, Morales R, Pageot N, Danel-Brunaud V, Vandenberghe N, Pradat PF, Couratier P, Salachas F, Lumbroso S, Rouleau GA, Meininger V, Camu W. Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations. Neurology. 2012 May 8;78(19):1519-26. doi: 10.1212/WNL.0b013e3182553c88. Epub 2012 Apr 25.
• Results Blasco H, Corcia P, Moreau C, Veau S, Fournier C, Vourc'h P, Emond P, Gordon P, Pradat PF, Praline J, Devos D, Nadal-Desbarats L, Andres CR. 1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis. PLoS One. 2010 Oct 8;5(10):e13223. doi: 10.1371/journal.pone.0013223.
• Results Arlicot N, Vercouillie J, Ribeiro MJ, Tauber C, Venel Y, Baulieu JL, Maia S, Corcia P, Stabin MG, Reynolds A, Kassiou M, Guilloteau D. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. 2012 May;39(4):570-8. doi: 10.1016/j.nucmedbio.2011.10.012. Epub 2011 Dec 14.
• Results Corcia P, Ingre C, Blasco H, Press R, Praline J, Antar C, Veyrat-Durebex C, Guettard YO, Camu W, Andersen PM, Vourc'h P, Andres CR. Homozygous SMN2 deletion is a protective factor in the Swedish ALS population. Eur J Hum Genet. 2012 May;20(5):588-91. doi: 10.1038/ejhg.2011.255. Epub 2012 Jan 25.
• Results Corcia P, Tauber C, Vercoullie J, Arlicot N, Prunier C, Praline J, Nicolas G, Venel Y, Hommet C, Baulieu JL, Cottier JP, Roussel C, Kassiou M, Guilloteau D, Ribeiro MJ. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941. doi: 10.1371/journal.pone.0052941. Epub 2012 Dec 31.

Drugs

Indications