Research: Myelin DNA vaccination and Black Holes


Papadopoulou A, von Felten S, Traud S, Rahman A, Quan J, King R, Garren H, Steinman L, Cutter G, Kappos L, Radue EW. Evolution of MS lesions to black holes under DNA vaccine treatment. J Neurol. 2012 Jan [Epub ahead of print]

Magnetic resonance Black Hole

Persistent black holes (PBH) as assessesd by MRI 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.

RESULTS: 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.

Ideas start as science fiction and can become science fact and lead to useful outcomes or can become science fanasty and be sucked in the black hole of failed ideas

Black hole of Science sucking in Failed ideas

To date there has been no clear evidence that DNA vaccination against myelin basic protein has any real influence on the course of multiple sclerosis and it is therefore not surprising that the generalised analysis of magnetic resonance imaging essentially shows that there is no influnece of this treatment on how black holes develop.

They then looked at serum antibodies to myelin basic protein and in this subgroup analysis appeared to find that higher antibody levels were correlated with a reduced the risk of persistent black holes.

In their preclinical studies efficacy of DNA vaccination was associated with a reduced immune response and not an enhanced immune response. Treatment efficacy has been associated with reductions of anti-myelin antibody responses, so we are left with the thought of whether this is a really a protective antibody response or that the two events are not biologically linked and it is a case of ice cream sales and shorts (We wear more shorts in summer and eat more ice cream when it is hot, but wearing shorts doesn’t make you eat ice cream!).

The real challenge is to show that BHT-3009 has a positive effect on the course of MS

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