Axerion’s NoGo decoy approach

Axerion’s NoGo decoy approach

Recovery of function following a Spinal Cord Injury (SCI) injury can be extremely limited.

Extracellular growth inhibitors prevent the growth of nerve fibers in the adult mammalian central nervous system (CNS) due in part to the presence of myelin-associated neurite growth inhibitors such as Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp). These growth inhibitors reside on oligodendrocytes and bind to axonal receptors including Nogo Receptor (NgR1). Bound NgR1 effectively inhibits axon growth in the CNS.

After spinal cord injury, healthy tissue remains both above and below the area of injury. If this remaining healthy tissue can be “rewired” with appropriate axonal connections, improved neurological function can result. The formation of new connections and the recovery of function after injury depend upon new axonal extensions from remaining cells, however, the growth inhibitors prevent axonal growth from occurring. With no treatment, axonal growth will be extremely limited in the adult brain and spinal cord, and recovery is typically restricted.

Axerion Therapeutics is developing a decoy receptor which consists of the ectodomain of NgR1 fused to IgG1.  This molecule, known as NgR(310)ecto-Fc binds to all three ligands (Nogo-A, MAG and OMgp), effectively blocking axonal growth inhibition. When the axonal growth inhibition is blocked, axonal growth can occur, which, in turn leads to the potential for recovery of function.

Published studies have documented the efficacy of NgR(310)ecto-Fc fusion protein in rodent models of spinal cord injury injury. Axon growth has been demonstrated in rodents with spinal cord injury (SCI), either from transection or from contusion injury. This renewed axon growth has led to increased function in animals after SCI.

Other therapeutic areas which may benefit from Nogo receptor decoy treatment include traumatic brain injury, ischemic stroke recovery, optic nerve damage and chronic progressive multiple sclerosis.

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