Last Updated: 2007-08-13 16:00:25 -0400 (Reuters Health)

NEW YORK (Reuters Health) – Vaccination with DNA encoding myelin basic protein can induce immune tolerance and reduce inflammatory brain lesions in patients with multiple sclerosis, the results of a phase 1/2 trial indicate.

"We have demonstrated in this first, to our knowledge, in-human trial of a DNA vaccine for autoimmune disease that the approach is safe and well tolerated," Dr. Amit Bar-Or, from Montreal Neurological Institute, and colleagues conclude in their report in the August 13th online issue of the Archives of Neurology.

The researchers explain that DNA vaccines not only generate an immune response against the protein they encode, but also "can be used instead to down-regulate or alter an ongoing immune response," as the team has demonstrated in animal models of autoimmunity.

The current study involved 30 patients with relapsing-remitting or secondary progressive multiple sclerosis who were randomized to receive the active vaccine, designated BHT-3009, or placebo at weeks 1, 3, 5, and 9. Eligibility criteria included having 1 to 5 gadolinium-enhancing lesions on brain MRI and relapse or disease worsening within the last 2 years.

Three dose levels of BHT-3009 were evaluated (0.5, 1.5, and 3 mg) and doses were given alone or in combination with atorvastatin, which has been shown to have beneficial T helper cell effects in preclinical studies.

Treatment with BHT-3009 was safe and well tolerated, Dr. Bar-Or’s team reports. In addition, its use was associated with a marked reduction in interferon-gamma-producing, myelin-reactive T helper cells in peripheral blood and with a drop in myelin-specific autoantibodies in cerebrospinal fluid. At the same time, a reduction in inflammatory brain lesions was noted.

There appeared to be no benefit to adding atorvastatin to vaccination, the researchers note.

Bar-Or’s team also found that treatment-related adverse events were mild or moderate. "Furthermore, the percentage of patients with adverse events in the BHT-3009 treatment arm was no greater than that with placebo."

"Based on these encouraging results, a 1-year, double-blind, randomized, placebo-controlled phase 2b trial of BHT-3009 in approximately 290 patients with relapsing-remitting multiple sclerosis has commenced," the investigators report.

Arch Neurol 2007;64.

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