General360 wrote "We recently heard about a particular type of MS, i'm wondering about our litlte miracle RVX-208 and it's impact on inflammation in general, MS and Rab32 in particular."

When did we hear about RVX-208 and multiple sclerosis (MS)? A recent Resverlogix news release highlighted a potential for RVX-208 in Facioscapulohumeral Muscular Dystrophy and in Neurodegenerative Eye Disease/Retinal Degeneration, but no mention of MS. 

The anti-inflammatory effects of RVX-208 might have a role in alleviating the inflammation and increased Rab32 levels observed in MS. However, so far the only connection of Resverlogix to multiple sclerosis was the work with RVX-297 (see citation below). It is very likely that Resverlogix and/or Zenith have advanced their pre-clinical programs with autoimmune diseases even further since then. If Rab32 is indeed a marker for MS, then it wouldn't be very hard for Resverlogix and/or Zenith to go back to their samples and measure Rab32 levels.

 R. Jahagirdar, S. M., S. Attwell, K. G. McLure, P. R. Young, H. C. Hansen, R. Yu, K. Norek, G. S. Wagner, An Orally Bioavailable Small Molecule RVX-297 Significantly Decreases Disease in a Mouse Model of Multiple Sclerosis (Poster Presentation). World Congress of Inflammation, Paris, France, 2011.

"We have discovered a representative of a novel chemical scaffold (RVX-297) that prevents and treats established autoimmune disease. In vitro, RVX-297 inhibited LPS-induced IL-6 expression in human U937 cells (IC50 of 0.9 µM) and T-cell receptor activation-induced IL-17 expression in human PBMCs (IC50 of 2.3 µM). In vivo, RVX-297 treated B6 mice (75 mg/kg, PO) had 93% lower serum concentrations of IL-6 compared to the vehicle-treated controls, 4 hours after 5 µg of LPS injection. RVX-297 was further evaluated in murine experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) that is known to be dependent on IL-6 and IL-17, to determine its potential to modulate autoimmune disease in vivo. EAE was induced in B6 mice via immunization with MOG35-55 and pertussis toxin injection. Oral administration of RVX-297 from the time of immunization prevented EAE development dose-dependently from 75-150 mg/kg b.i.d. Therapeutic administration of RVX-297 from the time of disease onset greatly reduced clinical signs of EAE dose dependently from 75-125 mg/kg b.i.d dose. The efficacy of RVX-297 treatment when administered to mice either prophylactically or therapeutically was comparable or superior to the S1P1 agonist, FTY720. Further analysis of spleen and lymph node culture supernatants from mice immunized with MOG35-55 and treated with RVX-297 found greatly reduced ex-vivo antigen-induced production of IL-6, IFN-γ, TNF and IL-17A protein (70%, 99%, 80% and 80% respectively) compared to the vehicle-treated controls. Gene expression analysis of ex-vivo cultures demonstrated up to 90% inhibition of IL-17, IFN-γ, IL-1, IL-21 and IL-4 mRNA. These cumulative results suggest that RVX-297 inhibits Th1 and Th17 responses which are believed to play a critical role in the development and pathology of autoimmune diseases. Therefore, compounds from this scaffold represent potential novel therapeutics for the treatment of autoimmune diseases including MS."

BDAZ