Yale University has received a USD 3.3 million NIH UG3 grant to advance a Phase II clinical trial of AXER-204, a Nogo-66 Receptor 1 (NgR1) pathway inhibitor, combined with rehabilitative training in patients with chronic incomplete cervical spinal cord injury (SCI) — marking a significant step toward the first pharmacologic neural repair therapy for a condition affecting roughly 300,000 Americans.
The award, issued May 26, 2026 by the National Institute of Neurological Disorders and Stroke (NINDS) under funding opportunity PAR-25-054, supports a double-blind, randomized, placebo-controlled trial enrolling 60 patients across six US sites. The study builds directly on the RESET trial, a first-in-human intrathecal AXER-204 study in chronic cervical SCI that demonstrated safety and cerebrospinal fluid biomarker changes consistent with neuroplasticity. Post-hoc analysis of RESET suggested motor strength gains in patients with incomplete injury, providing the clinical rationale for this next-stage effort.
AXER-204 is a soluble decoy receptor — designated NgR(310)ecto-Fc — that blocks NgR1, a pathway known to suppress axon regeneration and plasticity in the adult central nervous system. Rodent and non-human primate studies have shown that NgR1 blockade promotes neural repair and functional recovery following both transection and contusion SCI models. The new trial will enroll only patients with incomplete injury classified as AIS grades B, C, or D, a refinement based on RESET data showing greater responsiveness in this subgroup.
Rehabilitation as a synergistic component
A key design feature is the mandatory inclusion of rehabilitative training for all participants, coupling pharmacotherapy with structured physical therapy. The trial's primary efficacy endpoint is upper extremity motor strength; secondary outcomes include functional performance and activities of daily living. The investigators frame rehabilitation as mechanistically complementary, citing preclinical and clinical evidence that activity-dependent plasticity may amplify AXER-204's neuroplasticity-promoting effects.