TY  - JOUR
AU  - Hutchison, R Matthew
AU  - Fraser, Kyle
AU  - Yang, Minhua
AU  - Fox, Tara
AU  - Hirschhorn, Elizabeth
AU  - Njingti, Edwin
AU  - Scott, David
AU  - Bedell, Barry J
AU  - Kistner, Kristi M
AU  - Cedarbaum, Jesse M
AU  - Evans, Karleyton C
AU  - Graham, Danielle
AU  - Martarello, Laurent
AU  - Mollenhauer, Brit
AU  - Lang, Anthony E
AU  - Dam, Tien
AU  - Beaver, John
TI  - Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial.
JO  - Neurology
VL  - 102
IS  - 5
SN  - 0028-3878
CY  - [Erscheinungsort nicht ermittelbar]
PB  - Ovid
M1  - DZNE-2024-00146
SP  - e209137
PY  - 2024
AB  - Sensitive, reliable, and scalable biomarkers are needed to accelerate the development of therapies for Parkinson disease (PD). In this study, we evaluate the biomarkers of early PD diagnosis, disease progression, and treatment effect collected in the SPARK.Cinpanemab is a human-derived monoclonal antibody binding preferentially to aggregated forms of extracellular α-synuclein. SPARK was a randomized, double-blind, placebo-controlled, phase 2 multicenter trial evaluating 3 cinpanemab doses administered intravenously every 4 weeks for 52 weeks with an active treatment dose-blind extension period for up to 112 weeks. SPARK enrolled 357 participants diagnosed with PD within 3 years, aged 40-80 years, ≤2.5 on the modified Hoehn and Yahr scale, and with evidence of striatal dopaminergic deficit. The primary outcome was change from baseline in the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale total score. Secondary and exploratory biomarker outcomes evaluated change from baseline at week 52 relative to placebo. Dopamine transporter SPECT and MRI were used to quantify changes in the nigrostriatal dopamine pathway and regional atrophy. CSF and plasma samples were used to assess change in total α-synuclein levels, α-synuclein seeding, and neurofilament light chain levels. SPARK was conducted from January 2018 to April 2021 and terminated due to lack of efficacy.Approximately 3.8
KW  - Humans
KW  - Parkinson Disease: diagnostic imaging
KW  - Parkinson Disease: drug therapy
KW  - alpha-Synuclein
KW  - Antiparkinson Agents: therapeutic use
KW  - Antibodies, Monoclonal: therapeutic use
KW  - Dopamine: metabolism
KW  - Biomarkers
KW  - Disease Progression
KW  - Double-Blind Method
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Antiparkinson Agents (NLM Chemicals)
KW  - Antibodies, Monoclonal (NLM Chemicals)
KW  - Dopamine (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38315945
DO  - DOI:10.1212/WNL.0000000000209137
UR  - https://pub.dzne.de/record/267500
ER  -