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Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy

ABSTRACT: Background: Promising results from recent clinical trials on the approved antisense oligonucleotide nusinersen in pediatric patients with 5q-linked spinal muscular atrophy (SMA) still have to be confirmed in adult patients but are hindered by a lack of sensitive biomarkers that indicate an early therapeutic response. Changes of the overall neurochemical composition of cerebrospinal fluid (CSF) under therapy may yield additive diagnostic and predictive information. Methods: In this prospective proof-of-concept and feasibility study, we evaluated non-targeted CSF proteomic profiles by mass spectrometry along with basic CSF parameters of ten adult patients with SMA types II or III before and after ten months of nusinersen therapy, in comparison with ten age- and gender-matched controls. These data were bioinformatically analyzed and correlated with clinical outcomes assessed by the Hammersmith Functional Rating Scale Expanded (HFMSE). Results: CSF proteomic profiles of patients with SMA differed from controls. Two groups of SMA patients were identified based on unsupervised clustering. These groups differed in age and expression of proteins related to neuroregeneration or neurodegeneration. Intraindividual CSF differences in response to nusinersen treatment varied between patients who clinically improved and those who did not. Conclusions: Comparative CSF proteomic analysis in adult SMA patients before and after treatment identified subgroups and treatment-related changes and may therefore be suitable for diagnostic and predictive analysis. These results require verification in larger multicenter cohorts.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Not Available

SUBMITTER: Tobias Kessler

LAB HEAD: Wolfgang Wick

PROVIDER: PXD015117 | Pride | 2019-12-18

REPOSITORIES: Pride

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Cerebrospinal fluid proteomic profiling in nusinersen-treated patients with spinal muscular atrophy

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