PT  - JOURNAL ARTICLE
AU  - Streeter, Heather B.
AU  - Rigden, Rachel
AU  - Martin, Keith F.
AU  - Scolding, Neil J.
AU  - Wraith, David C.
TI  - Preclinical development and first-in-human study of ATX-MS-1467 for immunotherapy of MS
AID  - 10.1212/NXI.0000000000000093
DP  - 2015 Jun 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e93
VI  - 2
IP  - 3
4099  - http://nn.neurology.org/content/2/3/e93.short
4100  - http://nn.neurology.org/content/2/3/e93.full
SO  - Neurol Neuroimmunol Neuroinflamm2015 Jun 01; 2
AB  - Objective: The study was designed to test the efficacy of ATX-MS-1467 in a relevant preclinical model and to assess its safety for the treatment of patients with secondary progressive multiple sclerosis (SPMS).Methods: ATX-MS-1467 was tested for its ability to suppress experimental autoimmune encephalomyelitis (EAE) in the (Ob x DR2)F1 mouse both before and after disease onset. Safety was assessed by clinical assessment, MRI analysis, and the measurement of immune responses to self- and nonself-antigens in patients with SPMS.Results: ATX-MS-1467 displayed a dose-dependent inhibition of EAE and was more effective than glatiramer acetate in the treatment of ongoing disease in humanized mice. A phase 1 open-label dose-escalating study demonstrated that ATX-MS-1467 was safe and well-tolerated in a group of 6 patients with SPMS, up to a dose of 800 µg.Conclusions: The results of this study support further development of ATX-MS-1467 in a clinical trial powered to investigate the immunologic and clinical benefits of treatment in relapsing-remitting MS.Classification of evidence: This study provides Class IV evidence that ATX-MS-1467 is safe and tolerated in a group of 6 patients with SPMS.AE=adverse event; APC=antigen-presenting cells; BCG=bacillus Calmette-Guérin; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; GA=glatiramer acetate; HLA=human leukocyte antigen; IFN=interferon; IL=interleukin; IMP=investigational medicinal product; MBP=myelin basic protein; MHC=major histocompatibility complex; MS=multiple sclerosis; PBMC=peripheral blood mononuclear cells; PPD=purified protein derivative; SPMS=secondary progressive MS