Pubblicazioni

Autori:

Zink, Annika; Dai, Dao-Fu; Wittich, Annika; Henke, Marie-Thérèse; Pedrotti, Giulia; Heiduschka, Sonja; Santamaria, Guillem; Pentimalli, Tancredi Massimo; Brueser, Christian; Notopoulou, Sofia; Umar, Abdul Rahim; Zhaivoron, Aleksandra; Petersilie, Laura; Jerred, Caleb; Bergmans, Jesper; Neu, Louis Anton; Schumacher, Fabian; Keller-Findeisen, Jan; Rybak-Wolf, Agnieszka; Stach, Daniel; Reinshagen, Jeanette; Haferkamp, Undine; Krieg, Kim; Zaliani, Andrea; Euro, Liliya; Di Donfrancesco, Alessia; Santanatoglia, Chiara; Cappellozza, Enrica; Suarez Cubero, Marta; Pavez-Giani, Mario; Bakumenko, Oleh; Meierhofer, David; Foley, Alan; Morales-Gonzalez, Susanne; Tolle, Isabella; Herebian, Diran; Bonesso, Daniele; Cecchetto, Giulia; Wong, Sakurako Nagumo; Moresco, Monica; Maresca, Alessandra; Decimo, Ilaria; De Sanctis, Francesco; Adamo, Annalisa; Adjobo-Hermans, Merel J W; Duchi, Roberto; Barandalla, Maria; Scaglia, Marco; Perota, Andrea; Galli, Cesare; Kleuser, Burkhard; Cyganek, Lukas; Mühlhausen, Chris; Schlotawa, Lars; Tiranti, Valeria; Mayatepek, Ertan; Szabo, Ildiko; La Morgia, Chiara; Klopstock, Thomas; Carelli, Valerio; Distelmaier, Felix; Rossi, Andrea; Rajewsky, Nikolaus; Ullah, Ghanim; Jakobs, Stefan; Rose, Christine R; Petrakis, Spyros; Edenhofer, Frank; Koopman, Werner J H; Lisowski, Pawel; Suomalainen, Anu; Brunetti, Dario; Del Sol, Antonio; Bottani, Emanuela; Pless, Ole; Schuelke, Markus; Prigione, Alessandro

Titolo:

Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy

Anno:

2026

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

No

Nome rivista:

CELL

ISSN Rivista:

0092-8674

N° Volume:

189

Numero o Fascicolo:

6

Intervallo pagine:

1656-1679

Parole chiave:

Leigh syndrome; PDE5 inhibitors; PRKG1; brain organoids; drug repurposing; drug screening; high-content analysis; iPSCs; mitochondrial diseases; sildenafil

Breve descrizione dei contenuti:

: Mitochondrial disease encompasses inherited disorders affecting mitochondrial function. A severe and untreatable form of mitochondrial disease is Leigh syndrome (LS), causing psychomotor regression and metabolic crises. To accelerate drug discovery for LS, we screen a library of 5,632 repurposable compounds in neural cells from LS-patient-derived induced pluripotent stem cells (iPSCs). We identify phosphodiesterase type 5 (PDE5) inhibitors as leads and prioritize sildenafil for its clinical safety. Sildenafil corrects mitochondrial membrane potential defects, restores neurodevelopmental pathways, and normalizes calcium responses in LS brain organoids. In small and large mammalian models of LS, sildenafil extends lifespan and ameliorates disease phenotypes. Off-label treatment on an individual basis with sildenafil in six LS patients improves their motor function and resistance to metabolic crises. Collectively, the findings highlight the potential of iPSC-driven drug discovery and position sildenafil as a promising drug candidate for mitochondrial disease.

Note:

Epub 2026 Mar 11

Id prodotto:

150360

Handle IRIS:

11562/1186271

ultima modifica:

17 maggio 2026

Citazione bibliografica:

Zink, Annika; Dai, Dao-Fu; Wittich, Annika; Henke, Marie-Thérèse; Pedrotti, Giulia; Heiduschka, Sonja; Santamaria, Guillem; Pentimalli, Tancredi Massimo; Brueser, Christian; Notopoulou, Sofia; Umar, Abdul Rahim; Zhaivoron, Aleksandra; Petersilie, Laura; Jerred, Caleb; Bergmans, Jesper; Neu, Louis Anton; Schumacher, Fabian; Keller-Findeisen, Jan; Rybak-Wolf, Agnieszka; Stach, Daniel; Reinshagen, Jeanette; Haferkamp, Undine; Krieg, Kim; Zaliani, Andrea; Euro, Liliya; Di Donfrancesco, Alessia; Santanatoglia, Chiara; Cappellozza, Enrica; Suarez Cubero, Marta; Pavez-Giani, Mario; Bakumenko, Oleh; Meierhofer, David; Foley, Alan; Morales-Gonzalez, Susanne; Tolle, Isabella; Herebian, Diran; Bonesso, Daniele; Cecchetto, Giulia; Wong, Sakurako Nagumo; Moresco, Monica; Maresca, Alessandra; Decimo, Ilaria; De Sanctis, Francesco; Adamo, Annalisa; Adjobo-Hermans, Merel J W; Duchi, Roberto; Barandalla, Maria; Scaglia, Marco; Perota, Andrea; Galli, Cesare; Kleuser, Burkhard; Cyganek, Lukas; Mühlhausen, Chris; Schlotawa, Lars; Tiranti, Valeria; Mayatepek, Ertan; Szabo, Ildiko; La Morgia, Chiara; Klopstock, Thomas; Carelli, Valerio; Distelmaier, Felix; Rossi, Andrea; Rajewsky, Nikolaus; Ullah, Ghanim; Jakobs, Stefan; Rose, Christine R; Petrakis, Spyros; Edenhofer, Frank; Koopman, Werner J H; Lisowski, Pawel; Suomalainen, Anu; Brunetti, Dario; Del Sol, Antonio; Bottani, Emanuela; Pless, Ole; Schuelke, Markus; Prigione, Alessandro, Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy «CELL» , vol. 189 , n. 6 , 2026 , pp. 1656-1679

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo