Professor Stanford University Stanford, California, United States
Disclosure(s):
Gary K. Steinberg, MD, PhD: Peter Lazic, US: Royalty Recipient (Ongoing); SanBio: Consultant (Ongoing); Surgical Theatre: Consultant (Ongoing); Zeiss: Consultant (Ongoing)
Introduction: Currently, no treatment exists to restore function in chronic stroke patients. NR1 is a human embryonic derived neural stem cell that improved motor-sensory function in rodent stroke models. The aim is to assess the safety, tolerability and efficacy using intracerebral NR1 cell transplantation in chronic stroke patients (NCT04631406).
Methods: Inclusion Criteria: 18-75 yo; 6-60 months post-ischemic subcortical MCA stroke; mRS 3-4. Subjects are transplanted with NR1 (2.5M, 5M, 10M or 20M). Primary Outcomes: Adverse events 0-6 mos; Change in Fugl-Meyer (FM) motor score (maximum FM 100) compared to baseline at 6 & 12 months (≥10 points improvement considered “clinically meaningful”). Other outcomes: Gait Speed test, Barthel Index, NIHSS, mRS, MRI DTI, FLAIR, Resting State fMRI and [18F]FDG PET.
Results: Eight patients have been transplanted. Adverse events included headache, nausea and worsened speech, all resolving spontaneously. At 6 mos FM improved 13, 13, 8 and 7 points in 4 patients (all with faster gait); Barthel Index improved 5, 10, 15 and 5 points. At 3 mos FM improved 4 points (with faster gait) in 1 patient and at 2 mos FM improved 9 points (with faster gait) in 1 patient. At 6 mos NIHSS improved 2 points in 2 patients, was unchanged in 1 patient and worsened 1 point in 1 patient. 6/7 patients demonstrated new transient FLAIR signal in premotor cortex at d7, that resolved by 2 mos, which in prior studies correlated with sustained neurologic recovery. On resting state fMRI an increase in regional homogeneity indicating improved functional connectivity was observed in the sensorimotor network both ipsilateral and contralateral to the chronic infarction in a patient with clinical improvement.
Conclusion : Intraparenchymal transplantation with NR1 cells in chronic stroke patients appears safe and well tolerated. Early results suggest improved motor function at 1-6 months post-implant.
