Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models
Has received: March 4, 2021
Accepted: December 17, 2021
We thank S. Koks for providing the colony founders and G. Lutfalla (LPHI, Montpellier, France) for the PCS2+ Plasmid mCherry. This work was a project (#15) of the behavioral phenotyping platform CompAn (Montpellier, France). We thank the behavioral phenotyping platform ZebraSens (MMDN) and the breeding platform of the University of Montpellier (RAM-CECEMA). We thank the Montpellier Institute of Neuroscience animal facility and the Montpellier Animal Facility Network (RAM) for their assistance in animal husbandry and handling. We also thank A. Peyrel for his technical assistance.
Funding: This work was supported in part by external resources from the University of Montpellier (Fondation Pour l’Audition FPA RD-2019-13, Association Retina France and Fondation à BD) and in part by the Intra-muros Research Program of the National Institute of Drug Addiction. /NIH (at T.-PS). PP is grateful to Camilla degli Scrovegni for her continued support. PP is supported by the Italian Association for Cancer Research (AIRC: IG-23670), Associazione Ricerca Oncologica Sperimentale Estense (A-ROSE), Progetti di Rilevante Interesse Nazionale (PRIN2017E5L5P3) and local funds from the University of Ferrara. SP is supported by the Fondazione Umberto Veronesi. LC is supported by the Wolfram Syndrome Association and the Occitanie Region and Elodie M. Richard by The Snow Foundation and Eye Hope Foundation.
Author’s contributions: BD, TM and T.-PS designed the project and designed the experiments. LC performed most of the in vivo experiments and analyses. CD, MD and MR performed visual motor response experiments. NC took care of the zebrafish. AD and SP performed in vitro experiments on aequorin and hippocampus. YY and SC performed biochemical and histological experiments. AD, SP and PP performed in vitro experiments and analyses. J.-CL performed zebrafish injections. T.-PS allowed access to S1R KO and NG-108 cells. BD and TM performed part of the in vivo experiments on mice, prepared the figures and wrote the manuscript. EMR implemented the manuscript. All authors contributed to the preparation of the figures and to the drafting of the manuscript.
Competing interests: TM has been a consultant for Zogenix and Prilenia Therapeutics and holds patents on sigma-1 drugs (Novel phosphinolactone derivatives and Pharmaceutical Uses, WO2017191034A1; Sigma-1 receptor ligands and uses their, EP19306705; Sigma-1 receptor ligands and uses their, EP19306706 ). BD and TM have filed a patent (Sigma-1 receptor activator for use in the treatment of a pathology associated with the wfs1 mutation, EP pending 21306072.6). All other authors declare that they have no competing interests.
Availability of data and materials: All data associated with this study is present in the article or supplementary documents. A material transfer agreement between Karlsruhe IUT and Inserm ADR Montpellier exists for wfs1aC799X and wfs1bW493X zebrafish lines.