title: CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS.
abstract: OBJECTIVE
  This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the α subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  In a multicenter, double-blind, placebo-controlled randomized phase II trial, 77 patients with RRMS were treated with 200 mg of ATL1102 subcutaneously injected 3 times in the first week and twice weekly for 7 weeks or placebo and monitored for a further 8 weeks. MRI scans were taken at baseline and weeks 4, 8, 12, and 16. The primary endpoint was the cumulative number of new active lesions (either new gadolinium-enhancing T1 lesions or nonenhancing new or enlarging T2 lesions) at weeks 4, 8, and 12.
  
  
  RESULTS
  A total of 72 patients completed the study and 74 intention-to-treat patients were assessed. ATL1102 significantly reduced the cumulative number of new active lesions by 54.4% compared to placebo (mean 3.0 [SD 6.12] vs 6.2 [9.89], p = 0.01). The cumulative number of new gadolinium-enhancing T1 lesions was reduced by 67.9% compared to placebo (p = 0.002). Treatment-emergent adverse events included mild to moderate injection site erythema and decrease in platelet counts that returned to within the normal range after dosing.
  
  
  CONCLUSIONS
  In patients with RRMS, ATL1102 significantly reduced disease activity after 8 weeks of treatment and was generally well-tolerated. This trial provides evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders.
  
  
  METHODS
  This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions.
authors.affiliation: From the Department of Neurology (V.L.), Cologne City Hospitals, University of Cologne, Germany; the Department of Radiology (F.B.), VU Medical Centre, Amsterdam, the Netherlands; and Antisense Therapeutics Ltd. (N.D., M.P.D., G.T.), Melbourne, Australia.
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
authors.affiliation: From the Department of Neurology (V.L.), Cologne City Hospitals, University of Cologne, Germany; the Department of Radiology (F.B.), VU Medical Centre, Amsterdam, the Netherlands; and Antisense Therapeutics Ltd. (N.D., M.P.D., G.T.), Melbourne, Australia.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: From the Department of Neurology (V.L.), Cologne City Hospitals, University of Cologne, Germany; the Department of Radiology (F.B.), VU Medical Centre, Amsterdam, the Netherlands; and Antisense Therapeutics Ltd. (N.D., M.P.D., G.T.), Melbourne, Australia.
authors.forename: Nuket
authors.initials: N
authors.lastname: Desem
authors.affiliation: From the Department of Neurology (V.L.), Cologne City Hospitals, University of Cologne, Germany; the Department of Radiology (F.B.), VU Medical Centre, Amsterdam, the Netherlands; and Antisense Therapeutics Ltd. (N.D., M.P.D., G.T.), Melbourne, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Diamond
authors.affiliation: From the Department of Neurology (V.L.), Cologne City Hospitals, University of Cologne, Germany; the Department of Radiology (F.B.), VU Medical Centre, Amsterdam, the Netherlands; and Antisense Therapeutics Ltd. (N.D., M.P.D., G.T.), Melbourne, Australia. george.tachas@antisense.com.au.
authors.forename: George
authors.initials: G
authors.lastname: Tachas
mesh_terms: D000293:Adolescent; D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D039441:Integrin alpha4 / Q000737:chemistry* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D039441:Integrin alpha4