Journal of Neurology

, Volume 259, Issue 7, pp 1375–1382

Evolution of MS lesions to black holes under DNA vaccine treatment

  • Athina Papadopoulou
  • Stefanie von Felten
  • Stefan Traud
  • Amena Rahman
  • Joanne Quan
  • Robert King
  • Hideki Garren
  • Lawrence Steinman
  • Gary Cutter
  • Ludwig Kappos
  • Ernst Wilhelm Radue
Original Communication

DOI: 10.1007/s00415-011-6361-x

Cite this article as:
Papadopoulou, A., von Felten, S., Traud, S. et al. J Neurol (2012) 259: 1375. doi:10.1007/s00415-011-6361-x

Abstract

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.

Keywords

Multiple sclerosis BHT-3009 DNA vaccine Persistent black holes 

Abbreviations

ABH

Acute black holes

CL

Candidate lesions

CSF

Cerebrospinal fluid

EDSS

Expanded Disability Status Scale

Gd

Gadolinium

MBP

Myelin basic protein

MS

Multiple sclerosis

MSSS

MS Severity Score

MTR

Magnetization transfer ratio

NAA

N-Acetyl aspartate

NAGM

Normal appearing grey matter

NAWM

Normal appearing white matter

NUM

Number of human MBP peptide epitopes recognized by serum antibodies

PBH

Persistent black holes

PD-w SE

Proton density-weighted sequence

RRMS

Relapsing remitting multiple Sclerosis

T1-w SE

T1-weighted sequence

Supplementary material

415_2011_6361_MOESM1_ESM.jpg (39 kb)
Supplementary Fig. 1. Two examples of patients with ABH at week 8 and outcome at week 48 (isointense or PBH). Left panel: Patient with two enhancing CL at baseline (week 8: first row), one with ring enhancement and one with nodular enhancement, both mildly hypointense on the T1-w pre-contrast sequence (ABH). At end-point MRI (week 48: second row), both ABH have become T1-isointense. Right panel: Patient with a CL at baseline (week 8: first row), with ring Gd-enhancement, appearing as mildly hypointense on the T1-w pre-contrast SE (ABH). At week 48 (second row), the CL remained T1-hypointense (PBH). The MRI sequences in both examples are (from left to right): T1-weighted Sequence pre-contrast, T1-weighted Sequence post-contrast and Proton Density-weighted Sequence. (JPEG 38 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Athina Papadopoulou
    • 1
  • Stefanie von Felten
    • 2
  • Stefan Traud
    • 3
  • Amena Rahman
    • 4
  • Joanne Quan
    • 4
  • Robert King
    • 4
  • Hideki Garren
    • 4
  • Lawrence Steinman
    • 5
  • Gary Cutter
    • 6
  • Ludwig Kappos
    • 1
  • Ernst Wilhelm Radue
    • 3
  1. 1.Neurology Clinic, Department of NeurologyUniversity Hospital BaselBaselSwitzerland
  2. 2.Clinical Trial UnitUniversity Hospital BaselBaselSwitzerland
  3. 3.Medical Image Analysis Center (MIAC)University Hospital BaselBaselSwitzerland
  4. 4.Bayhill TherapeuticsPalo AltoUSA
  5. 5.Stanford UniversityStanfordUSA
  6. 6.Department of BiostatisticsUniversity of AlabamaBirminghamUSA

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