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.
Department of Neurology, University Hospital Basel, Petersgraben, Basel, Switzerland. papadopouloua@uhbs.ch
Athina
A
Papadopoulou
Stefanie
S
von Felten
Stefan
S
Traud
Amena
A
Rahman
Joanne
J
Quan
Robert
R
King
Hideki
H
Garren
Lawrence
L
Steinman
Gary
G
Cutter
Ludwig
L
Kappos
Ernst Wilhelm
EW
Radue
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D004676:Myelin Basic Protein / Q000276:immunology; D016017:Odds Ratio; D013997:Time Factors; D019444:Vaccines, DNA / Q000627:therapeutic use*; D055815:Young Adult
C544595:BHT 3009; D007075:Immunoglobulin M; C499048:MBP protein, human; D004676:Myelin Basic Protein; D019444:Vaccines, DNA