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Multiple sclerosis, NeuroVax vaccine stimulates increase in FOXP3 gene and Treg cell functional activity


The results from an ongoing clinical study demonstrated investigational T-cell receptor ( TCR ) peptide vaccine, NeuroVax, stimulates a significant increase in FOXP3, a gene marker recently shown to track regulatory T-cells ( Treg cells ).

The new data showed that monthly NeuroVax injections during a one-year period increased the FOXP3 marker and Treg cell functional activity in multiple sclerosis ( MS ) patients to a level equivalent to that seen in healthy controls.

Recently published research indicates that FOXP3, known to be associated with maintaining immune tolerance and regulation of autoimmune diseases, is significantly reduced in patients with multiple sclerosis compared to healthy controls.

" These preliminary results are an important indication that NeuroVax(TM) can restore Treg cell activity that may help reestablish regulatory control of pathogenic inflammatory T-cells," said Arthur A. Vandenbark, at the Portland Veterans Affairs Medical Center, and at Oregon Health & Science University in Portland.. " Successful boosting of Treg cell activity may reduce the immune system attack on the myelin sheath that contributes to the MS disease progression."

The preliminary results were based on the nine NeuroVax treated patients who have completed the 52-week study. Patients were analyzed at baseline and at 52 weeks, and were compared to a group of gender and age-matched healthy controls.

Autoimmune diseases such as multiple sclerosis may result from the failure of tolerance mechanisms to prevent expansion of pathogenic inflammatory T-cells.
Previous research indicated that MS patients have abnormalities in FOXP3 message and protein expression levels in peripheral Treg cells.
This observation linked a defect in functional peripheral immunoregulation to an established genetic marker, FOXP3, previously shown to be associated with maintaining immune tolerance and preventing development of autoimmune diseases.
Diminished FOXP3 levels indicate impaired immunoregulation by Treg cells that may contribute to MS.
The induction of these Treg cells is believed important to the mechanism of action for NeuroVax. The new data indicates for the first time that treatment with NeuroVax does stimulate FOXP3 Treg cells.

NeuroVax combines three TCR peptides with IFA ( Incomplete Freund's Adjuvant ).

Source: 15th European Neurological Society ( ENS ) Meeting, 2005


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