MONTREAL -- An investigational tolerizing DNA vaccine for multiple sclerosis, BHT-3009, was safe and well tolerated in a 30-patient trial, researchers here found.
MONTREAL, Aug. 14 -- An investigational tolerizing DNA vaccine for multiple sclerosis, BHT-3009, was safe and well tolerated in a 30-patient trial, researchers here found.
Moreover, the vaccine induced antigen-specific immune tolerance and MRI showed evidence of a reduction of inflammatory lesions, according to an early online release of a paper that will be published in the October issue of Archives of Neurology.
BHT-3009 encodes a full-length human myelin basic protein, wrote
Amit Bar-Or, M.D., of the Montreal Neurological Institute and colleagues.
For their 30-patient trial, they recruited volunteers with confirmed relapsing-remitting MS or secondary progressive MS. The patients were randomized to placebo, BHT-3009 alone, or BHT-3009 plus 80 mg atorvastatin (Lipitor). Participants received intramuscular injections at weeks one, three, five, and nine.
The vaccine was tested at 0.5 mg, 1.5 mg. and 3 mg. After 13 weeks patients in the placebo group were crossed over to active vaccine and received four injections.
MRI was conducted at baseline and again after five, nine, 13, 26, 38, and 50 weeks.
Antigen specific changes include a reduction in the number of cytokine-producing CD4+ T cells specifically targeting myelin proteins found in both the blood and cerebrospinal fluid of three patients who underwent lumbar puncture after completing the course of BHT-3900.
The authors said there was no additional benefit observed for patients given BHT-3900 plus high dose atorvastatin. They had theorized that atorvastatin could potentiate the efficacy of the vaccine based on promising results from animal trials and early-stage human trials.
MRI detected no increase in the number of gadolinium-enhancing lesions, volume of gagolinium enhancing lesions, or volume of T2 lesions. "Rather, there was a trend toward a reduction in lesion activity after treatment relative to the placebo group," they wrote.
They pointed out, however, that "one consideration in interpreting the MRI data is that a relatively higher number of patients with [secondary progressive] MS without relapses were randomized to placebo, and thus conclusions solely based on the MRI data should be avoided."
The authors said that based on these "encouraging results" they have already begun a 290-patient phase 2b trial of the vaccine.
"If successful in MS, antigen-specific DNA vaccines can be developed for prevention or treatment of related diseases, such as type 1 diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis," they concluded.