0000000000267674
AUTHOR
Eleonora Dalla Bella
The MITOS system predicts long-term survival in amyotrophic lateral sclerosis
ObjectiveThe choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.MethodsAnalyses were performe…
Protein misfolding, amyotrophic lateral sclerosis and guanabenz: Protocol for a phase II RCT with futility design (ProMISe trial)
IntroductionRecent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumula…