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The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.

Author: AbgueguenEmmanuelle, AntoniniGiovanni, BersanoEnrica, BorgheroGiuseppe, CapassoMargherita, CaponnettoClaudia, ChiòAdriano, CorboMassimo, Dalla BellaEleonora, FilostoMassimiliano, FurlanRoberto, GianniniFabio, LauriaGiuseppe, LunettaChristian, MandrioliJessica, MessinaSonia, MonsurròMaria Rosaria, MoraGabriele, NolanJohn M, RivaNilo, RizziRomana, SicilianoGabriele, SilaniVincenzo, SimoneIsabella, SorarùGianni, SpataroRossella, TramacereIrene, TugnoliValeria, VerrielloLorenzo, VolantiPaolo

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

This study investigated the safety and efficacy of guanabenz, an endoplasmic reticulum stress inhibitor, in patients with amyotrophic lateral sclerosis (ALS). The results suggest that guanabenz may slow disease progression, particularly in patients with bulbar onset, but with potential side effects.
Paper Details　
Original Abstract of the Article :
Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eI...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557337/

データ提供：米国国立医学図書館（NLM）

Targeting Endoplasmic Reticulum Stress in Amyotrophic Lateral Sclerosis (ALS)

This study delves into the complex world of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease. Researchers are exploring various therapeutic approaches, including those that target the unfolded protein response (UPR), a cellular mechanism that plays a crucial role in the pathogenesis of ALS. The study investigated the efficacy and safety of guanabenz, a drug that specifically inhibits the eIF2α-phosphatase, a key enzyme involved in the UPR pathway. Guanabenz was previously shown to reduce neuronal death and prolong survival in preclinical models. This study aimed to evaluate its potential in patients with ALS.

Guanabenz Shows Promise in Treating ALS, Particularly in Patients with Bulbar Onset

The study involved a multicenter, randomized, double-blind trial with a futility design. Patients with ALS were randomly assigned to receive different doses of guanabenz or placebo for 6 months. The study found that guanabenz, particularly at higher doses (64 mg and 32 mg), showed non-futility in terms of slowing down disease progression. This positive effect was particularly observed in patients with bulbar onset, where guanabenz significantly delayed disease progression compared to placebo or historical cohorts. While guanabenz showed promise, it also led to an increased incidence of adverse events, particularly at higher doses.

A Glimpse of Hope for ALS Patients: Potential Treatment Strategies

The findings suggest that further research into the UPR pathway for ALS is warranted. The study's results, particularly for patients with bulbar onset, highlight the potential of guanabenz as a therapeutic agent. However, the need to address the side effect profile and develop alternative drugs targeting the UPR pathway without the alpha-2 adrenergic related side-effects is crucial. Think of this research like a camel navigating a treacherous desert landscape; while there are obstacles and challenges, the potential for a life-changing oasis is worth exploring.

Dr. Camel's Conclusion

This study offers a promising avenue for treating ALS, particularly for patients with bulbar onset. While guanabenz shows potential, further research is needed to develop safe and effective drugs that target the UPR pathway. Finding a cure for ALS is like searching for a hidden spring in a vast desert; it requires persistence, innovation, and a willingness to explore uncharted territories.
Date :
  1. Date Completed 2021-12-14
  2. Date Revised 2021-12-14
Further Info :

Pubmed ID

33905493

DOI: Digital Object Identifier

PMC8557337

SNS
PICO Info
in preparation
Languages

English

Positive IndicatorAn AI analysis index that serves as a benchmark for how positive the results of the study are. Note that it is a benchmark and requires careful interpretation and consideration of different perspectives.

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