Amyotrophic Lateral Sclerosis: Precise Diagnosis and Individualized Treatment

IntroductIon Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of upper motor neurons (UMNs) and lower motor neurons (LMNs), typically may die from respiratory failure within 2–5 years of symptom onset.[1] About 10% of ALS patients are familial whereas the remaining patients are sporadic. ALS is highly heterogeneous in genetic and clinical phenotype, with lack of definitive diagnostic tools, making it extremely difficult to make early diagnosis. Considerable resources have been devoted to unravel the pathogenesis of ALS since the first pathogenic gene SOD1 was found in 1993. With the advances in sequencing and genome technology, the pace of pathogenic gene discovery has been greatly accelerated. At present, more than 20 ALS genes including SOD1, TARDBP, FUS, C9ORF72, OPTN, VCP, UBQLN2, PFN1, TBK1, and CHCHD10 have been discovered.[2,3] Several potential molecular pathways leading to motor neuron degeneration have been identified.[4] Although riluzole and edaravone (RADICAVA) have been shown to slow the disease progression and have a modest improvement in survival by several months,[5] currently, ALS is still lack of effective cures. Here, we discuss the problems in precise diagnosis and individualized treatment of ALS patients.