DNA Vaccination for Multiple Sclerosis: Phase I/II Trial Results
Clinical trials have previously tried to induce tolerance in multiple sclerosis by selectively inducing immune response against the autoreactive T cells, with some degree of effect.
The current clinical trial that we will discuss here uses immunization with a DNA vaccine encoding myelin basic protein to induce antigen-specific tolerance, or inhibition of immunity. It was published as a collaboration between the company Bayhill Therapeutics, and several academic centers (Bar-Or et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch Neurol 2007 Oct;64(10):1407-15).
Since myelin basic protein is what the immune system is attacking in multiple sclerosis, or at least one of the main targets, the idea was that if myelin basic protein could be administered intramuscularly, or better said, expressed intramuscularly, then through the immune system may actually be suppressed in response to it. Below is a picture of the plasmid that was used for injection.
This study is interesting because it is, to our knowledge, the first time that DNA vaccination was used for induction of immunological tolerance in patients in an antigen-specific manner. Unfortunately, the lack of actual efficacy in MRI lesion size, or even lack of symptomological improvement (it was not discussed), suggests that numerous other modifications, or at least large sample sizes, need to be performed to see an effect.
On a positive note, one of the interesting features of this study was that even though the antigen myelin basic protein was administered as a “tolerogen”, inhibition of immune responses against other autoantigens, such as PLP. This suggests that the immune system may be somehow “re-educating itself”. We proposed the concept of “epitope spreading” in the context of immune regulation many years ago, and this may be an excellent example.
Given that autologous stromal vascular fraction contains antiinflammatory cells in addition to regenerative mesenchymal stem cells, it may be worthwhile to see whether adipose non-expanded stem cell therapy affects epitope spreading both from the pathogenic and regulatory perspective.