Here is a recent abstract from Active related to laquinimod in a rat model - hints that this might be synergistic with ifn-beta:
J Neuroimmunol. 2006 Apr;173(1-2):69-78.
Epub 2006 Feb 10.
Inhibition of the development of chronic experimental autoimmune encephalomyelitis by laquinimod (ABR-215062) in IFN-beta k.o. and wild type mice.
* Runstrom A,
* Leanderson T,
* Ohlsson L,
* Axelsson B.
Active Biotech AB, Box 724, SE-220 07 Lund, Sweden. anna.runstrom@activebiotech.com
Laquinimod is a novel oral immunomodulatory substance, which is currently developed for the treatment of multiple sclerosis (MS). The ability of laquinimod to inhibit disease development was investigated in chronic experimental autoimmune encephalomyelitis (chEAE) in IFN-beta k.o. mice and wild type mice. Laquinimod was shown to inhibit both disease development and histopathological changes in the CNS. Furthermore, laquinimod was found to be independent of endogenous IFN-beta for its effect in chEAE. When laquinimod was combined with exogenous IFN-beta, a synergistic disease inhibitory effect was seen. These findings using laquinimod in preclinical disease models for MS emphasize the potential of laquinimod in the future treatment of MS also in patients that do not respond to IFN-beta monotherapy. Furthermore, the results indicate that laquinimod may favourably be combined with IFN-beta.
And an older publication hinting at mode of action:
J Neuroimmunol. 2004 Nov;156(1-2):3-9.Click here to read Links
Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats.
* Yang JS,
* Xu LY,
* Xiao BG,
* Hedlund G,
* Link H.
Division of Neuroimmunology, NEUROTEC Department, Karolinska Institute, Stockholm, Sweden.
The new orally active drug laquinimod (ABR-215062) was evaluated in experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. EAE shares important immunological and clinical features with multiple sclerosis (MS). Doses of 16, 1.6 and 0.16 mg/kg/day laquinimod dose-dependently inhibited disease and showed better disease inhibitory effects as compared to roquinimex (Linomide). Furthermore, laquinimod inhibited the inflammation of both CD4+ T cells and macrophages into central nervous tissues, i.e. the spinal cord. It also changed the cytokine balance in favour of TH2/TH3 cytokines IL-4, IL-10 and TGF-beta. Laquinimod therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties with a potential for the treatment of severe autoimmune diseases like MS. |
