Nature Communications (Feb 2023)
LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice
- Ramachandran Prakasam,
- Angela Bonadiman,
- Roberta Andreotti,
- Emanuela Zuccaro,
- Davide Dalfovo,
- Caterina Marchioretti,
- Debasmita Tripathy,
- Gianluca Petris,
- Eric N. Anderson,
- Alice Migazzi,
- Laura Tosatto,
- Anna Cereseto,
- Elena Battaglioli,
- Gianni Sorarù,
- Wooi Fang Lim,
- Carlo Rinaldi,
- Fabio Sambataro,
- Naemeh Pourshafie,
- Christopher Grunseich,
- Alessandro Romanel,
- Udai Bhan Pandey,
- Andrea Contestabile,
- Giuseppe Ronzitti,
- Manuela Basso,
- Maria Pennuto
Affiliations
- Ramachandran Prakasam
- Dulbecco Telethon Institute at the Department of Cellular, Computational and Integrative Biology, University of Trento
- Angela Bonadiman
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Roberta Andreotti
- Department of Biomedical Sciences, University of Padova
- Emanuela Zuccaro
- Department of Biomedical Sciences, University of Padova
- Davide Dalfovo
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Caterina Marchioretti
- Department of Biomedical Sciences, University of Padova
- Debasmita Tripathy
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Gianluca Petris
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Eric N. Anderson
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Alice Migazzi
- Dulbecco Telethon Institute at the Department of Cellular, Computational and Integrative Biology, University of Trento
- Laura Tosatto
- Dulbecco Telethon Institute at the Department of Cellular, Computational and Integrative Biology, University of Trento
- Anna Cereseto
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Elena Battaglioli
- Department of Medical Biotechnology and Translational Medicine, University of Milan
- Gianni Sorarù
- Padova Neuroscience Center
- Wooi Fang Lim
- MDUK Oxford Neuromuscular Centre, University of Oxford
- Carlo Rinaldi
- MDUK Oxford Neuromuscular Centre, University of Oxford
- Fabio Sambataro
- Padova Neuroscience Center
- Naemeh Pourshafie
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Christopher Grunseich
- National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Alessandro Romanel
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Udai Bhan Pandey
- Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
- Andrea Contestabile
- Istituto Italiano di Tecnologia
- Giuseppe Ronzitti
- Université Paris-Saclay, Univ Evry, Inserm, Genethon
- Manuela Basso
- Department of Cellular, Computational and Integrative Biology, University of Trento
- Maria Pennuto
- Dulbecco Telethon Institute at the Department of Cellular, Computational and Integrative Biology, University of Trento
- DOI
- https://doi.org/10.1038/s41467-023-36186-9
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 22
Abstract
Here, Prakasam and colleagues show that polyQ-expanded androgen receptor toxicity can be attenuated using artificial miRNAs targeting Lsd1 and Prmt6, two AR-co-activators overexpressed in an androgen-dependent manner specifically in skeletal muscle, thus ameliorating spinal-bulbar muscular atrophy phenotypes in flies and mice.
