Time for optimism in amyotrophic lateral sclerosis

Abstract

Background and purpose Amyotrophic lateral sclerosis (ALS) is among the most common motor neuron diseases in adults. Nevertheless, ALS remains fatal, despite decades of research and clinical trials, which has led to negative conclusions until recently in regard to four specific treatments. It is well known that we can learn from failures, and we consider that the time has come to present positive insight on this disease. Methods We did a literature search using PubMed and Scopus for articles published in English from 1 January 2016, to 30 June 2022 dealing with “amyotrophic lateral sclerosis”, diagnosis, treatment, and biomarkers. Results A comprehensive review of the literature on diagnosis, monitoring, and treatment of this condition showed convincing evidence that we are now able to diagnose earlier as well as to better monitor and treat ALS. Conclusions Although ALS is often difficult to diagnose and remains incurable, there are many indications that an optimistic view of ALS management in the coming years is now realistic.

Proteomic profiling of the brain from the <i>wobbler</i> mouse model of amyotrophic lateral sclerosis reveals elevated levels of the astrogliosis marker glial fibrillary acidic protein

“…The results from systematic proteomic profiling studies of both the brain and skeletal musculature can now be used to establish new biomarker candidates to improve diagnostic and prognostic approaches 14 and identify novel therapeutic targets to treat the highly complex neuromuscular pathogenesis of amyotrophic lateral sclerosis. 47 Besides evaluating tissue-related changes in motor neuron disease, an important aspect of biomarker research is the identification of biofluid markers in serum or cerebrospinal fluid. 14 , 48 Biofluid markers of clinical interest include GFAP and neurofilament light chain.…”

Population-based Evidence for Using Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

“…Given the evolving pipeline of potential disease-modifying treatments in ALS, reducing the diagnostic delay and optimizing the effectiveness of phase 2 and 3 trials have become key challenges 7 . Our study shows that serum NfL is a marker of interest for both domains.…”

“…Multiple sclerosis is regarded as the pioneer disease for neuro lament establishment; here, NfL is used to monitor disease activity and therapy response and acts as a prognostic biomarker 5,6 . In contrast to multiple sclerosis, therapeutic options for treating amyotrophic lateral sclerosis (ALS) or other neurodegenerative diseases, such as Alzheimer's disease, are still limited; however, positive signals from recent studies and the promising pipeline of therapies currently investigated in clinical trials provide reasonable hope for improving treatment opportunities in the next decade 7 .…”

Population-based Evidence for the Use of Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

“…Given the evolving pipeline of potential disease-modifying treatments for ALS, reducing the diagnostic delay and optimising the effectiveness of phase 2 and 3 trials have become key challenges 34 . Our study shows that serum NfL in particular is a marker of interest for both domains, but also highlights the need to consider disease progression rates and phenotype as ALS-related factors and age, BMI, renal function and sex as non-ALS confounders.…”