[Biomarkers for amyotrophic lateral sclerosis]

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder. Modern technology has brought new insights in the underlying pathophysiology of ALS through examination of genomic, proteomic and physiological changes in patients. However, the diagnosis of this disorder is still based on clinical findings, and there is a pronounced delay between the onset of symptoms and diagnosis. Functional rating scales, forced vital capacity, and patient survival have been used as measures of therapeutic response so far. Although effective treatments for ALS are lacking, the discovery of biomarkers for this disease offers clinicians the tools for rapid diagnosis, improved ways to monitor disease progression, and insights into the pathophysiology of sporadic ALS. Potential biomarkers that are useful in the diagnosis of ALS and sensitive to the progression of disease, which might enhance the diagnostic algorithm and provide new drug targets, are now being eagerly investigated through blood and cerebrospinal fluid analyses, as well as physiological and neuroimaging studies. These biomarkers, when used in combination, might be sensitive to early therapeutic effects. Such biomarkers might also resolve complexities of phenotypic heterogeneity in clinical trials. In this review article, I have discussed the development of biochemical, physiological and neuroimaging biomarkers for ALS including our recent results on CSF TDP-43 (TAR DNA-binding protein 43 kDa), and have considered the potential future directions for research. We should ultimately aim to broaden the available therapeutic options for patients with this disease.