, Volume 259, Issue 7, pp 1375-1382
Date: 06 Jan 2012

Evolution of MS lesions to black holes under DNA vaccine treatment

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Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5 mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5 mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo (p < 0.01). Although we found no overall reduction of the risk for PBH in treated patients, there may be an effect of low-dose BHT-3009, depending on the patients’ pre-treatment immune responses.

Part of the results of this study was presented as a poster-presentation at the 25th Congress of the European committee for treatment and research in multiple sclerosis (ECTRIMS) in Düsseldorf, Germany, in September 2009. Session: immunomodulation-2, P820: “Conversion of new inflammatory lesions to persistent black holes in patients with relapsing multiple sclerosis participating in a phase II trial of DNA vaccine encoding myelin basic protein (BHT-3009)”.