Objective: We aim to predict both treatment efficacy and disease progression in PD patients with subthalamic nucleus deep brain stimulation therapy (STN-DBS) by genotyping of single nucleotide polymorphisms in the alpha-synuclein (SNCA, 3’UTR, rs356219 and rs356220; n=85) and leucine-rich kinase (LRRK2, rs1491923; n=71) genes.

Background: Patient stratification for STN-DBS is highly warranted given both the clinical heterogeneity of sporadic Parkinson’s disease (PD) and the variability of individual treatment outcomes.

Methods: We analyzed 85 PD patients with STN-DBS on treatment efficacy using the preoperative UPDRSIII score in ‘medication off’ and the ‘medication off, stimulation on’ UPDRSIII score at the first two-year interval after STN-DBS. We used linear regression analyses on an additive genotype model and treated ‘gender’, ‘disease duration at DBS surgery’, and ‘allele carrier status’ as independent variables.

Results: SNCA minor allele variants indicated more favorable response of motor symptoms to STN-DBS two years from implantation with stronger improvement in homozygous as compared to heterozygous carriers of the minor SNCA allele variant. Stratification for LRRK2 genotypes did not yield predictive value. Neither SNCA nor LRRK2 variants were predictive for postoperative motor symptom progression.

Conclusions: This study identifies SNCA variants as candidate biomarkers to assist stratification for neurostimulation therapy.

DGN (German Society for Neurology).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-gene-variants-may-predict-neurostimulation-outcome/