Portal de Periódicos da CAPES

Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial

2024; Oxford University Press; Volume: 6; Issue: 5 Linguagem: Inglês

10.1093/braincomms/fcae304

2632-1297

Giulia Gianferrari, Riccardo Cuoghi Costantini, V. Crippa, Serena Carra, Valentina Bonetto, Orietta Pansarasa, Cristina Cereda, Elisabetta Zucchi, Ilaria Martinelli, Cecilia Simonini, Roberto Vicini, Nicola Fini, Francesca Trojsi, Carla Passaniti, Nicola Ticozzi, Alberto Doretti, Luca Diamanti, Giuseppe Fiamingo, Amelia Conte, Eleonora Dalla Bella, Eustachio D’Errico, Eveljn Scarian, Laura Pasetto, Francesco Antoniani, Veronica Galli, Elena Casarotto, Jessica Mandrioli, Nicola Fini, Ilaria Martinelli, Elisabetta Zucchi, Giulia Gianferrari, Cecilia Simonini, Francesca Prompicai, Silvia Parisi, Roberto D’Amico, Federico Banchelli, Roberto Vicini, Riccardo Cuoghi Costantini, Angelo Poletti, V. Crippa, Elena Casarotto, Serena Carra, Laura Mediani, Francesco Antoniani, Veronica Galli, Valentina Bonetto, Laura Pasetto, Orietta Pansarasa, Eveljn Scarian, Cristina Cereda, Francesca Trojsi, Carla Passaniti, Vincenzo Silani, Nicola Ticozzi, Alberto Doretti, Luca Diamanti, Giuseppe Fiamingo, Mario Sabatelli, Amelia Conte, Giulia Bisogni, Giuseppe Lauria, Eleonora Dalla Bella, Nilo Riva, Enrica Bersano, Isabella Laura Simone, Eustachio D’Errico, Roberto D’Amico, Angelo Poletti, Jessica Mandrioli,

Parkinson's Disease Mechanisms and Treatments

In preclinical studies, the anti-inflammatory drug colchicine, which has never been tested in amyotrophic lateral sclerosis, enhanced the expression of autophagy factors and inhibited accumulation of transactive response DNA-binding protein 43 kDa, a known histopathological marker of amyotrophic lateral sclerosis. This multicentre, randomized, double-blind trial enrolled patients with probable or definite amyotrophic lateral sclerosis who experienced symptom onset within the past 18 months. Patients were randomly assigned in a 1:1:1 ratio to receive colchicine at a dose of 0.005 mg/kg/day, 0.01 mg/kg/day or placebo for a treatment period of 30 weeks. The number of positive responders, defined as patients with a decrease lesser than 4 points in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score during the 30-week treatment period, was the primary outcome. Disease progression, survival, safety and quality of life at the end of treatment were the secondary clinical outcomes. Secondary biological outcomes included changes from baseline to treatment end of stress granule and autophagy responses, transactive response DNA-binding protein 43 kDa, neurofilament accumulation and extracellular vesicle secretion, between the colchicine and placebo groups. Fifty-four patients were randomized to receive colchicine (