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出版Universität, 2022
URLhttp://books.google.com.hk/books?id=f3ebzwEACAAJ&hl=&source=gbs_api
註釋Abstract: Background
The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the last 4 years but treatment responses differ remarkably between individuals and therapeutic decision-making remains challenging - underlining the persistent need for validated biomarkers.

Methods
We applied untargeted proteomic analyses to determine biomarkers in cerebrospinal fluid (CSF) samples of SMA patients under treatment with nusinersen. Identified candidate proteins were validated in CSF samples of SMA patients by Western blot and ELISA. Further, levels of peripheral neurofilament H and L were determined.

Results
Untargeted proteomic analysis of CSF samples of 3 SMA type 1 patients revealed the lysosomal protease Cathepsin D as a candidate biomarker. Subsequent validation analysis in a larger cohort of 31 pediatric SMA patients (type 1=12, type 2=9, type 3=6, presymptomatically treated=4; age 0-16 years) revealed a significant decline of Cathepsin D levels in SMA patients ≥2 months at the start of treatment. While evident in all older age categories, this decline was only significant in the group of patients that showed a positive motor-response. Moreover, downregulation of Cathepsin D was evident in muscle biopsies of SMA patients.

Conclusions
We identified a decline of Cathepsin D levels in CSF samples of SMA patients under nusinersen treatment that was more pronounced in the group of 'treatment responders' than in 'non-responders'. We believe that our results indicate a suitability of Cathepsin D levels as possible biomarker in SMA also in older patients - in combination with analysis of pNF-L in adolescents or alone in adult patients