title: Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial).
abstract: The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple-System-Atrophy Parkinson-type (MSA-P). Sixty-three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple-System-Atrophy Rating-Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified-Parkinson's-Disease Rating-Scale (UPDRS). Health-related quality of life (HrQoL) was assessed using the EQ-5D and SF-12. "Progression rate" was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow-up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. "progression rate" was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[(11)C](R)-PK11195-PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)-PK11195 binding actually decreased. These preliminary PET-data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double-blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function.
authors.affiliation: Department of Neurology, Philipps-University of Marburg, 35039 Marburg, Germany. richard.dodel@med.uni-marburg.de
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.forename: Annika
authors.initials: A
authors.lastname: Spottke
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerhard
authors.forename: Alexander
authors.initials: A
authors.lastname: Reuss
authors.forename: Sylvia
authors.initials: S
authors.lastname: Reinecker
authors.forename: Nicole
authors.initials: N
authors.lastname: Schimke
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Friederike
authors.initials: F
authors.lastname: Sixel-Döring
authors.forename: Birgit
authors.initials: B
authors.lastname: Herting
authors.forename: Christoph
authors.initials: C
authors.lastname: Kamm
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Martin
authors.initials: M
authors.lastname: Sawires
authors.forename: Felix
authors.initials: F
authors.lastname: Geser
authors.forename: Martin
authors.initials: M
authors.lastname: Köllensperger
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.forename: Manja
authors.initials: M
authors.lastname: Kloss
authors.forename: Martin
authors.initials: M
authors.lastname: Krause
authors.forename: Christine
authors.initials: C
authors.lastname: Daniels
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.forename: Silke
authors.initials: S
authors.lastname: Böttger
authors.forename: Markus
authors.initials: M
authors.lastname: Naumann
authors.forename: Axel
authors.initials: A
authors.lastname: Lipp
authors.forename: Doreen
authors.initials: D
authors.lastname: Gruber
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
authors.forename: Federico
authors.initials: F
authors.lastname: Turkheimer
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Gregor
authors.initials: G
authors.lastname: Wenning
authors.forename: Carmen
authors.initials: C
authors.lastname: Schade-Brittinger
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Karla
authors.initials: K
authors.lastname: Eggert
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D019578:Multiple System Atrophy / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000523:psychology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods; D011788:Quality of Life; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007546:Isoquinolines; D018696:Neuroprotective Agents; D008911:Minocycline; C037850:PK 11195