[A prognostic biomarker in amyotrophic lateral sclerosis]

Area of Science:

• Neurology
• Biochemistry
• Biomarker Discovery

Background:

• Amyotrophic lateral sclerosis (ALS) requires more effective treatments beyond existing disease-modifying drugs.
• Current clinical outcome measures need supplementation with reliable, objective biomarkers for rigorous therapy testing.
• Existing biomarkers, including neurophysiological, neuroimaging, and fluid-based assays, have limitations in specificity, sensitivity, or cost-effectiveness.

Purpose of the Study:

• To review and highlight promising biomarker candidates for amyotrophic lateral sclerosis (ALS) research.
• To emphasize the need for exploring established and emerging biomarkers in clinical trials.
• To underscore the ongoing search for innovative and reliable biomarkers for ALS.

Main Methods:

• Review of existing literature on neurophysiological biomarkers, specifically transcranial magnetic stimulation (TMS).
• Evaluation of neuroimaging biomarkers for ALS diagnosis and disease progression.
• Analysis of fluid-based biochemical biomarkers, including creatinine (Crn), uric acid (UA), and neurofilaments (NF; pNFH and NFL).

Main Results:

• Transcranial magnetic stimulation (TMS) shows potential for exploring ALS disease mechanisms.
• Neuroimaging offers high specificity for ALS diagnosis but lacks sensitivity for tracking disease progression.
• Creatinine (Crn) and uric acid (UA) are cost-effective fluid biomarkers with potential for predicting ALS progression.
• Neurofilaments (NF), including phosphorylated-NF heavy subunit (pNFH) and NF light subunit (NFL), are sensitive diagnostic biomarkers but may be insensitive to disease changes over time.

Conclusions:

• Creatinine (Crn), uric acid (UA), and neurofilament (NF) biomarkers warrant extensive investigation in future ALS clinical trials.
• While promising, current biomarkers necessitate further exploration for optimal use in assessing ALS progression.
• The development of novel, innovative, and reliable biomarkers remains a critical objective for advancing ALS research and treatment.