The brain-penetrant ATM inhibitor, AZD1390, promotes axon regeneration and functional recovery in preclinical models of spinal cord injury

This study demonstrates that AZD1390, an orally bioavailable, brain-penetrant, potent, and highly selective inhibitor of ataxia–telangiectasia mutated (ATM), promotes dramatic recovery after spinal cord injury (SCI). AZD1390 engaged and suppressed its target and promoted dorsal root ganglion neuron (DRGN) neurite outgrowth in vitro and stimulated axon regeneration after SCI in vivo, with the recovery of conductance across the lesion site and led to remarkable improvements in sensory and locomotor function. The simple oral administration route and good safety profile suggests that AZD1390 is a potential new therapy to promote recovery of function after SCI in patients.

• 1
  Oral AZD1390 significantly suppresses pATM levels in dorsal root ganglia (DRG) at 4 weeks after DC injury.
• 2
  Oral AZD1390 treatment promoted axon regeneration through the lesion site and entry into the rostral cord.
• 3
  Oral AZD1390 significantly improved tape sensing and removal times and ladder crossing performance (locomotor function) over 6 weeks after DC injury.