RESUMEN
Although we currently have two, approved, disease-modifying drugs for the treatment of amyotrophic lateral sclerosis (ALS), we are in disperate need for more efficacious treatment. To aggressively test for newer therapies, we must develop reliable objective biomarkers to supplement clinical outcome measures. Many biomarker candidates have been actively and vigorously investigated. Among neurophysiological biomarkers, transcranial magnetic stimulation (TMS)-based biomarkers show potential in exploring disease mechanisms. Neuroimaging biomarkers have high specificity in diagnosing ALS but are an expensive endeavor and are not sensitive enough to detect changes over time of the disease. Among fluid-based biochemical biomarkers, creatinine (Crn) and uric acids (UA), which have been known for decades, may prove to be highly promising biomarkers that can predict disease progression. They can be easily tested in any clinical trials because the costs are minimal. Although known for some time, neurofilaments (NF), either phosphorylated-NF heavy subunit (pNFH) or NF light subunit (NFL), have emerged as "new" biomarkers using specific antibodies. They appear to be highly specific and sensitive in diagnosing ALS, yet they may be insensitive to assess changes in disease over time. These two NF biomarkers along with Crn and UA should be explored extensively in future clinical trials and any other clinical studies in ALS. Yet, we still need newer, more innovative, and reliable biomarkers for future ALS research. Fortunatley, aggressive investigations appear to be currently underway.