筋萎縮性側索硬化症のバイオマーカー

抄録

Many clinical trials have been conducted on amyotrophic lateral sclerosis (ALS) in recent years, and the importance of early diagnosis and intervention has been recognized once again. To achieve this, the development of more useful biomarkers for diagnosis and severity is required.

Diagnosis of ALS is made by confirming lower and upper motor neuron disorders and excluding other diseases. The usefulness of central motor conduction time (CMCT), short–interval intracortical inhibition (SICI), MR spectroscopy (MRS), and diffusion tensor imaging (DTI) has been reported for the evaluation of upper motor neuron disorders. If lower motor neuron damage is asymptomatic or mild, electromyography should be used to confirm the presence or absence. Neuromuscular ultrasound is also frequently used, and is particularly useful in determining the presence or absence of fasciculation throughout the body. In 2022, Kurashige et al. revealed from muscle biopsy findings that TDP43 accumulation in intramuscular nerve terminals is observed from a relatively early stage in ALS patients. Although muscle biopsy is not recommended in all cases, it may be useful for diagnosing TDP–ALS.

The ALS functional rating scale revised (ALSFRS–R) is widely used as an endpoint in ALS clinical trials but has some limitations, so biomarkers that reflect the severity are needed. Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are known liquid biomarkers and have already been used in several clinical trials.

Although these biomarkers are useful, there are still challenges, and the development of new biomarkers is desired.