脊髄小脳変性症のバイオマーカー開発をめざして

抄録

Molecular targeted therapies for the neurodegenerative diseases are currently being developed, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and spinocerebellar ataxias, some of which are now clinically tested in patients with these diseases. To evaluate the clinical efficacy of these drug candidates, it is necessary to develop pathological biomarkers that enable evaluation of drug efficacy during a short–term period of clinical trials. Compared to functional brain imaging biomarkers, biochemical biomarkers using body fluids, such as blood, cerebrospinal fluid, and urine, are highly versatile and advantageous, because they are relatively easy to collect and do not require special equipment for measurement. Current candidates for biochemical biomarkers for the neurodegenerative diseases include pathogenic proteins, such as amyloid–β, tau, α–synuclein, and ataxin–3, and neurofilament light chain (NF–L), which is thought to reflect neuronal damage. In addition, exosomes and other extracellular vesicles, which are secreted from cells and abundantly present in body fluids, have attracted much attention as a potential source of biomarkers, because they contain a variety of cellular proteins and RNAs and may change in response to the intracellular environment and pathological events. In this review, we will summarize the status of clinical development of therapies and biomarkers for spinocerebellar ataxias, and discuss the current issues on clinical samples for future biomarker development.