Recombinant Intrabodies as Molecular Tools and Potential Therapeutics for Amyotrophic Lateral Sclerosis

LE STUDIUM Multidisciplinary Journal, 2019, 3, 1-7

Dênis Reis de Assis1,5, Anna Chami1, Rudolf Hergesheimer1, Judith Halewa1, Seyedeh Tayebeh Ahmad Pour2, Débora Lanznaster1, Osbaldo López Charcas3, Lucie Brisson2, Maxime Gueguinou2, Sébastien Roger3, Jean-François Dumas2, Frédéric Laumonnier1, Patrick Vourc´h1,4, Hélène Blasco1,4


1UMR 1253, iBRAIN, Université de Tours, Inserm, Tours, France

2Université de Tours, Inserm, UMR1069 Nutrition, Croissance et Cancer, Tours, France

3Université de Tours, EA4245 Transplantation, Immunologie et Inflammation, Tours, France

4CHU de Tours, Service de Biochimie et Biologie Moléculaire, Tours, France

5 LE STUDIUM Institute for Advanced Studies, 45000 Orléans, France


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that has no diagnostic marker, prognosis, nor an effective treatment. Numerous physiopathological mechanisms have been described for this disease, such as glutamatergic excitotoxicity, oxidative stress, and the accumulation of protein aggregates in cells of the central nervous system, in particular the aggregation of cytoplasmic TDP-43.Our aim was targeting the protein aggregates containing TDP-43 through fragments of antibodies synthesized by the cell, termed intrabodies. In order to determine the most relevant criteria to test the protective effects of the intrabodies, we searched for different toxicity markers associated with TDP-43aggregates. During the fellowship, the fellow participated of 2 publications of the host laboratory in this field. Besides, at the end of the fellowship, the host Scientist and the Le Studium fellow organized a conference about iPS cells, a powerful tool to model in vitro neurodegenerative diseases such as ALS. In addition, the fellow generated preliminary results showing that TDP-43 overexpression in HEK 293 cells does not affect mitochondrial respiration, but causes an increase in cytoplasmic calcium levels, while impairs the mitochondrial capacity to buffer the excessive cytoplasmic calcium. Moreover, preliminary patch clamp data showed alterations in spontaneous currents in primary hippocampal and motor neurons overexpressing TDP-43. If these results are further confirmed, calcium signaling and spontaneous currents could be used as parameters to measure the efficacy of anti-TDP-43 intrabodies.


Patch clamp
Mitochondrial metabolism
Calcium signaling
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LE STUDIUM Multidisciplinary Journal