title: Randomized, double-blind, placebo-controlled trial of hydroxyurea in spinal muscular atrophy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1-T2) and then every 2 months throughout treatment (T3-T10) and posttreatment periods (T11-T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC).
  
  
  RESULTS
  Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had -1.88 for GMFM (p = 0.11), -0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function.
  
  
  CONCLUSIONS
  Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia.
  
  
  METHODS
  This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.
authors.affiliation: Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
authors.forename: T-H
authors.initials: TH
authors.lastname: Chen
authors.forename: J-G
authors.initials: JG
authors.lastname: Chang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Yang
authors.forename: H-H
authors.initials: HH
authors.lastname: Mai
authors.forename: W-C
authors.initials: WC
authors.lastname: Liang
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wu
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wang
authors.forename: Y-B
authors.initials: YB
authors.lastname: Huang
authors.forename: S-M
authors.initials: SM
authors.lastname: Wu
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
authors.forename: S-N
authors.initials: SN
authors.lastname: Yang
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Jong
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy* / Q000503:physiopathology; D009503:Neutropenia / Q000139:chemically induced; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D012333:RNA, Messenger / Q000378:metabolism; D017211:Treatment Failure; D014797:Vital Capacity / Q000187:drug effects; D055815:Young Adult
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D006918:Hydroxyurea