Scientists Demonstrate Investigational MS Drug Down Regulates the Underlying Cause Believed Responsible for Multiple Sclerosis
In a number of patients with myelin basic protein (MBP) specific active T cells, BHT-3009 was shown to down-regulate these T cells, the primary cause of MS, an autoimmune disease. Left unchecked, the MBP-specific T cells shred the protective myelin sheath that encases the neurons responsible for nerve transmission. The absence of the myelin sheath results in unpredictable and increasingly destructive short circuits in the body's central nervous system, critical to life function. While scientists don't yet know what causes this pathology in MBP-specific T cells, when these T cells become pathogenic, they cause MS. Bayhill's drug development specifically centers on shutting down the disease causing activity of these MBP-specific T cells. From pre-clinical concept to clinical demonstration, the specifically of Bayhill's DNA plasmid therapy has resulted in a strong safety profile.
“This is the first clinical trial of a DNA plasmid for antigen-specific immunotherapy of any autoimmune disease”
The Bayhill research is one of the first hints that scientists engaged in multiple sclerosis drug discovery can directly and specifically affect MBP-specific T cells in humans. In an ongoing placebo-controlled 30-patient Phase I/II investigation in relapsing MS patients, a team of Bayhill scientists and clinicians at four medical centers in North America have demonstrated antigen-specific reduction and desired effect, specifically affecting MBP T cells.
These data and findings were presented in a poster session at the 21st Congress of the European Committee for Treatment and Research of Multiple Sclerosis in Thessaloniki, Greece by Bayhill co-founder and Vice President of Research, Hideki Garren, MD, PhD: Antigen-specific immunomodulation in multiple sclerosis patients treated with MBP encoding DNA plasmid (BHT-3009) alone or combined with atorvastatin. The poster was one of five selected by peers to receive a prize for scientific novelty and clinical promise. The poster is located at: www.bayhilltx.com.
In order to assess whether the underlying autoimmune mechanism of pathogenesis is affected by the DNA vaccine, Bayhill scientists performed immune assays on peripheral blood, including T cell proliferation, using a CFSE-based antigen-specific, intracellular cytokine assay (CFSE/IC). The assay has shown potential correlation with MRI, the standard of care in measuring inflammation in the brain and progress of the disease. For this reason Bayhill believes the CFSE/IC assay to be clinically relevant.
Using the assay, the team observed:
-- MBP specific T cells can be detected in peripheral blood (as contrasted to the more invasive evaluation of the central nervous system) of MS patients using the CFSE/IC assay, and that there is some degree of correlation between brain MRI activity and MBP specific T cell reactivity. Bayhill scientists believe this is a breakthrough.
-- BHT-3009 reduces MBP specific T cell reactivity in a number of cases. In these patients, the team observed antigen-specific reduction in MBP reactive T cells by week 9 of treatment.
-- There is no indication of induction of immunity against MBP with BHT-3009. The significance of this finding is indicative of the safety of the BHT-3009 in that it does not activate the disease causing cells.
"This is the first clinical trial of a DNA plasmid for antigen-specific immunotherapy of any autoimmune disease," said Dr. Garren. "The preliminary data suggest that BHT-3009 can specifically decrease the activity of MBP reactive T cells. Additional clinical testing of BHT-3009 is warranted and needed, but we hope to eventually provide patients with a safe and disease specific option to fill the current void in MS treatments."
About Bayhill Therapeutics
Bayhill Therapeutics Inc., founded with technology developed in Professor Lawrence Steinman's laboratory at Stanford University, is focused on the translation of research into therapeutics by developing novel drugs for the treatment of autoimmune diseases. The company has established a therapeutic platform of BHT-DNA(TM) antigen-specific therapeutics, with broad potential applications in treating autoimmune diseases, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Bayhill's lead product in this platform, BHT-3009, is an antigen-specific DNA plasmid and is currently in early-stage clinical testing in multiple sclerosis patients. Bayhill is preparing for a phase II trial to begin in early 2006. In addition, Bayhill is developing a second therapeutic program, BHT-Oligo(TM) oligonucleotide based drugs, for treating autoimmune diseases. For further information, please visit: http://www.bayhilltx.com.