神経変性疾患と予防医療

抄録

Recent advancement in studies on pathogenesis led to development of disease–modifying therapies such as nucleic acid therapies for neuromuscular disorders. Such therapies target disease causing genes and proteins, but therapeutic benefits in clinic is limited at a symptomatic stage of disease. To overcome this, strategies for prevention have been actively developed for neurodegenerative disease. Before manifestation of core motor/cognitive symptoms, preclinical and then prodromal stages exist during the progression of neurodegeneration. At preclinical stage, molecular changes occurs but symptoms are hardly detectable. At prodromal stage, heralding symptoms appear prior to manifestation of core symptoms. In cohort studies on at–risk subjects, mild motor/cognitive symptoms emerge ∼20 years prior to the onset of subjective symptoms in various diseases. For instance, non–motor symptoms including REM sleep behavior disorder occurs approximately 15 years before clinical diagnosis of Parkinson disease, which is made on the basis of subjective motor symptoms. The effects of disease–modifying therapy for preventing neurodegeneration is clearly shown in a clinical trial of nusinersen, a nucleic acid therapy of spinal muscular atrophy, for pre–symptomatic subjects, in which initiation of disease–modifying therapy before manifestation achieved potent therapeutic effects particularly in mild patients. Currently, cohort studies, biomarker research, and novel therapies are being developed to further prevent various neurodegenerative diseases.