DNA Vaccination for Multiple Sclerosis: Phase I/II Trial Results
As we discussed here on StemNow.com, the possibility of antigen-specific tolerance for multiple sclerosis is, along with regenerative medicine, the most promising area of research in this field.
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.
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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.
Tags: antigen specific immune modulation, bayhill therapeutics, clinical trial, multiple sclerosis, myelin basic protein
June 15th, 2009 at 8:42 pm
I don’t see why this vaccination would not accelerate multiple sclerosis?
June 16th, 2009 at 12:00 am
[...] It will be interesting to elucidate the immunological mechanisms by which plasma exchange may mediate its effects, and if it may be incorporated into other immune modulatory therapies. Such a simple incorporation could be the combination of plasma exchange and antigen-specific immunization to achieve tolerance. We previously discussed here that immunization in the presence of inflammation or “danger” is often associated with immune activation, whereas introduction of antigen in absence of inflammation can be associated with tolerance. Therefore by “washing the body” of inflammatory agents, one may achieve even better effects with agents such as BioMS’s MBP8298 product or Bayhill Therapeutic’s myelin basic protein DNA vaccine called BHT-3021. [...]
June 16th, 2009 at 12:07 am
It does not accelerate it because it is inducing tolerance, I do not believe that it is known how, but it seems to be related to giving protein without giving inflammation. I bet if you started to scratch the skinn at the place of immunization you would get a worse disease.
Did you see thaty Bayhill therapeutics actually sold their diabetes platform that is the same thing, to Genentech?
Tanya
July 12th, 2009 at 4:42 pm
I would be interested in one of clinical trail for MS. Would you please contact me as soon as possbile. Wilma