DNA vaccines may offer hope in multiple sclerosis

Authors from the VA North Texas Health Care System Neurology Section and the Department of Neurology at the University of Texas Southwestern Medical Center at Dallas have highlighted the potential benefits for DNA-based vaccine administration in patients with multiple sclerosis (MS).

In a Perspective article published in the March issue of Expert Review of Neurotherapeutics, the authors draw attention to some recent promising observations and evaluate the potential for DNA vaccination in MS*.

Typically, DNA vaccines are composed of a bacterial plasmid that encodes a protein of specific interest behind a strong promoter (a DNA nucleotide sequence that forms a recognition site for the enzyme required for gene expression). The use of a DNA vaccine is considered the most simple or minimal way to induce an immune response.

Multiple sclerosis is an autoimmune inflammatory neurodegenerative disease of the central nervous system of unknown cause. The prevalence of the disease is known to be 1.1-2.5 million cases worldwide, and the disease is diagnosed in women twice as frequently as in men. Emerging evidence from recent studies suggests that aberrant immune-regulation is an important component in the pathogenesis of MS.

The authors, Drs Olaf Stüve, Petra Cravens and Todd Eager, draw attention to recent clinical studies involving BHT-3009, a DNA vaccine encoding full-length human myelin basic protein. MS is a demyelinating disease i.e. it involves degeneration of the myelin sheath surrounding axons - components of the neurons that make up nerve tissue. The authors highlight a recent safety trial with BHT-2009 - the first trial with a DNA vaccine for an autoimmune disease in human patients - which showed it to be safe and well tolerated, although clinical efficacy is, as yet, difficult to assess. However, a forthcoming Phase IIb clinical trial comparing two doses of BHT-3009 with placebo in 289 patients with relapsing-remitting multiple sclerosis (RRMS) promises to reveal more about the potential clinical benefits of this approach.

DNA vaccination has advantages over existing treatments - DNA vaccines are non-infectious, easily manufactured and inexpensive to produce. Subject to the outcome of the Phase IIb study, we may see the initiation of a Phase III study. Depending on the duration of that potential study, and provided that the use of BHT-3009 in a larger patient cohort can demonstrate safety and efficacy, the authors suggest that approval for its use in patients with RRMS could be possible within 5 years.

*DNA-based vaccines: the future of multiple sclerosis therapy. Stüve O, Cravens PA and Eager TN. Expert Review of Neurotherapeutics 8(3) 351-360 (2008)