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Clinical trials in ALS: an overview
M R Turner1, M J Parton, P N Leigh
1Department of Neurology, Institute of Psychiatry, London, UK.
Abstract:
Clinical trials in amyotrophic lateral sclerosis (ALS) have been conducted for over half a century now and have incorporated a wide variety of drugs. Most of these trials have had negative results and a cure remains elusive. The explosion in our understanding of molecular biology and parallel developments in clinical epidemiology have opened up a vast number of novel therapeutic strategies. However, advances in statistical analysis, computing, and global communications have also put greater pressure on scientific investigators to improve the design and implementation of clinical trials so that they permit rigorous testing of hypotheses within a solid ethical framework. This article documents the first published trial for all drugs tried clinically in the treatment of ALS, focusing in more detail on the large, multicenter trials of recent years, namely those involving riluzole, ciliary neurotrophic factor, insulin-like growth factor-I, brain-derived neurotrophic factor, and SR57746A. The problems in the design of trials in ALS are discussed, including the selection of end points and surrogate markers of disease progression, and the major parameters in ALS assessment are reviewed.
Insights
Clinical trials for amyotrophic lateral sclerosis (ALS) have yielded limited success, with most drugs failing to produce a cure. This review details past and recent ALS drug trials, highlighting challenges in trial design and assessment.
Area of Science:
- Neurology
- Clinical Epidemiology
- Drug Development
Background:
- Amyotrophic lateral sclerosis (ALS) research has a long history of clinical trials, yet a cure remains elusive.
- Despite numerous drug investigations, most clinical trials for ALS have yielded negative results.
- Advancements in molecular biology and epidemiology offer new therapeutic avenues for ALS.
Purpose of the Study:
- To document all published clinical trials for drugs tested in amyotrophic lateral sclerosis (ALS) treatment.
- To provide a detailed focus on recent large, multicenter trials involving specific novel therapeutic agents.
- To critically review the challenges and parameters in designing and assessing ALS clinical trials.
Main Methods:
- Comprehensive review of published clinical trial data for amyotrophic lateral sclerosis (ALS) treatments.
- Detailed analysis of large, multicenter trials for riluzole, ciliary neurotrophic factor, insulin-like growth factor-I, brain-derived neurotrophic factor, and SR57746A.
- Examination of trial design issues, including endpoint selection and surrogate markers for disease progression.
Main Results:
- Over fifty years of ALS clinical trials have explored numerous drugs with limited therapeutic success.
- Recent large-scale trials have investigated promising agents like riluzole and various growth factors.
- Significant challenges persist in optimizing ALS clinical trial design and outcome assessment.
Conclusions:
- Despite extensive research, effective treatments for amyotrophic lateral sclerosis (ALS) remain a significant challenge.
- Improvements in trial design, endpoint selection, and statistical analysis are crucial for future ALS drug development.
- A rigorous ethical framework and robust methodology are essential for advancing ALS therapeutics.