BioCentury
ARTICLE | Distillery Therapeutics

Neurology

August 9, 2017 6:36 PM UTC

Mouse studies suggest inhibiting the MKNK1-MKNK2-eIF4E axis could help treat pain. In a mouse model of inflammatory pain, knock-in of an elF4E variant that cannot be phosphorylated by MKNK1 or MKNK2 decreased mechanical hyperalgesia, mechanical allodynia and thermal allodynia compared with wild-type eIF4E expression. In a mouse model of chemical-induced pain, double MKNK1/MKNK2-knockout decreased mechanical and thermal allodynia and hyperalgesia compared with normal MKNK1/MKNK2 expression. In two other mouse models of chemical-induced pain, a dual MKNK1/MKNK2 inhibitor tool compound or knock-in of the phosphorylation-deficient eIF4E variant decreased mechanical allodynia and hyperalgesia compared with vehicle or wild-type eIF4E expression, respectively. In a mouse model of pain induced by spinal nerve injury, double MKNK1/MKNK2-knockout, the dual MKNK1/MKNK2 inhibitor or knock-in of the eIF4E variant decreased mechanical and thermal allodynia compared with normal MKNK1/MKNK2 expression, vehicle or wild-type eIF4E expression. Next steps by CerSci Therapeutics include testing MKNK1 inhibition as monotherapy in models of pain.

Effector Therapeutics Inc. has eFT508, a small molecule inhibitor of MKNK1 and MKNK2, in Phase I/II testing to treat lymphoma and advanced solid tumors...