Introduction
ALS
AMYOTROPHIC LATERAL SCLEROSIS 1, NEURODEGENERATIVE DISEASE
With a life-long risk of 1:400, Amyotrophic Lateral Sclerosis (ALS) is the 3rd most common neurodegenerative disease, holding an estimated increase of 69% in the upcoming yearsRapamycin, a drug used to prevent renal transplantation rejection, inhibits mammalian Target of Rapamycin Complex 1, leading to regulatory T lymphocytes (Treg) expansion and autophagy enhancement. In fact, mTOR inhibits the induction of Tregs, a specific cell population that down-regulates immune system activation and is found to be reduced and dysfunctional in ALS patientsFurthermore, several in vitro and in vivo studies also suggest that inhibition of mTOR by rapamycin may target autophagy, which is crucial not only for cell-autonomous clearance mechanisms, but also for limiting detrimental and uncontrolled activation of inflammasomesIn preclinical ALS studies, rapamycin reduced TDP-43 fragments accumulation and restored TDP-43 nuclear localization in cell linesHere we report the results of RAP-ALS, a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial (RCT), that evaluates safety, biological and clinical effects of oral rapamycin in persons with ALS