CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS.

Autor:	Limmroth V; 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., Barkhof F; 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., Desem N; 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., Diamond MP; 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., Tachas G; 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.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2014 Nov 11; Vol. 83 (20), pp. 1780-8. Date of Electronic Publication: 2014 Sep 19.
DOI:	10.1212/WNL.0000000000000926
Abstrakt:	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. Classification: This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions. (© 2014 American Academy of Neurology.)
Databáze:	MEDLINE
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