In December of 2016 Science Translational Medicine published new study where the authors introduced new, low-molecular weight compound that specifically inhibited autoimmune/allergic responses while sparing anti-pathogen immune response.
This new molecule, AX-024, specifically targets adaptor protein Nck that is involved in low affinity TCR signaling.
It does not affect signaling delivered via IL-2, BCR or PMA/Ion stimulation.
AX-024 inhibited TLR7/8 agonist, imiquimod (IMQ), induced psoriasis skin symptoms in mice.
Also, AX-024 significantly reduced clinical symptoms associated with mouse model of human multiple sclerosis (MS). Such effect of AX-024 was superior to Fingolimod, a sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing-remitting MS.
Notably, AX-024 in therapeutic dosage did not impair anti-pathogen immunity or memory generation.
In summary, by blocking Nck adaptor protein involved in low-affinity TCR signaling, AX-024 inhibited autoreactivity while preserving necessary capacity for anti-pathogen immunity. Such property makes it desirable candidate for clinical trials in humans.
David Usharauli
