Evolution of MS lesions to black holes under DNA vaccine treatment
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.
KeywordsMultiple sclerosis BHT-3009 DNA vaccine Persistent black holes
Acute black holes
Expanded Disability Status Scale
Myelin basic protein
MS Severity Score
Magnetization transfer ratio
Normal appearing grey matter
Normal appearing white matter
Number of human MBP peptide epitopes recognized by serum antibodies
Persistent black holes
- PD-w SE
Proton density-weighted sequence
Relapsing remitting multiple Sclerosis
- T1-w SE
The original study was supported by Bayhill Therapeutics. A. Papadopoulou takes full responsibility for the data, the analyses and interpretation, and the conduct of the research, has full access to all of the data, and has the right to publish any and all data separate and apart from any sponsor. We acknowledge the support of Pascal Kuster (MIAC, Basel, Switzerland) and Marcus Weber (Neurology Clinic, Basel, Switzerland) in technical issues as well as the advice and guidance through this study of Danilo Marzetti, Dr. Nicole Müller-Lenke, Dr. Kerstin Bendfeldt (MIAC, Basel, Switzerland) and Thomas Fabbro, PhD (Clinical Trial Unit, University Hospital Basel, Switzerland).
Conflicts of interest
The original study was supported by Bayhill Therapeutics. Athina Papadopoulou, Stefanie von Felten and Stefan Traud have no conflict of interest. Amena Rahman is paid as a consultant from Bayhill Therapeutics. Joanne Quan and Hideki Garren are employees of Bayhill Therapeutics and hold Bayhill stock options. Robert King is employed full-time by Bayhill Therapeutics and receives stock and financial compensation. Lawrence Steinman consults for Bayhill Therapeutics and serves on their Board of Directors. Gary Cutter has received Consulting, Speaking, & Advisory Boards fees from Bayhill Therapeutics. Ludwig Kappos’ institution has received payments for his participation as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. Sponsoring pharmaceutical companies for these trials include Bayhill Therapeutics. Ernst Wilhelm Radue has received research support (mainly for MS projects) from Bayhill Therapeutics.
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