First-in-Man Report of Acute Intra-Arterial Allogeneic Mesenchymal Stem Cell Therapy in Two Patients with Locked-In Syndrome Post-Thrombectomy:
Dileep Yavagal1, Aaron Rodriguez-Calienes2, Hassan Charles3, Vasu Saini4, Roshni Thakkar5, Charif Sidani3, Pradip Pattany3, Negar Asdaghi5, Aisha Khan3
1University of Miami Miller School of Medicine, 2Department of Neurology, University of Miami/Jackson Health System, 3University of Miami/Jackson Health System, 4Mount Sinai Medical Center, 5University of Miami
Background:
Complete Locked-in Syndrome (cLIS) from stroke is catastrophic, with <1% probability of significant motor recovery. In our pre-clinical canine model of reversible MCA stroke, we identified the maximum tolerated and effective dose of 40 million intra-arterial (IA) allogeneic mesenchymal stem cells (alMSCs).
Design/Methods:
Case 1: A 36-year-old man with basilar artery occlusion (BAO) and coma developed LIS despite successful EVT. Two doses of 20 million IA alMSCs (50% of the preclinical dose) were administered via the Penumbra 3 Max catheter into the proximal basilar artery at 4 and 14 days post-stroke.
Case 2: An 83-year-old man with BAO developed LIS after EVT. One dose of 20 million IA alMSCs was delivered at the vertebrobasilar junction at 6 days.
Results:
Case 1: No peri-procedural complications occurred. After the first dose, the patient experienced no neurological decline, though IL-6 levels spiked tenfold. MRI showed a 27cc reduction in infarct volume and NIHSS improved by 1 point, with new bilateral upper extremity withdrawal to pain. After the second dose and vertebral artery stenting, 4.5cc of new ischemia appeared on DWI, but without clinical worsening. At 6 months, the patient was off the ventilator and had improved facial, neck, and limb movement. At 27 months, he could follow commands, had silent verbalization, sat up, and self-fed with his right hand. NIHSS dropped from 27 to 9, mRS improved from 5 to 4, and MRI DTI showed marked improvement.
Case 2: No peri-procedural complications. Forty-eight hours post-treatment, DWI showed no new ischemia, but the NIHSS worsened by 7 points 4 days later due to fever and leucocytosis. Care was withdrawn on day 9.
Conclusions:
This first-in-man report of IA alMSCs in two cLIS stroke patients demonstrated favorable safety and a signal of benefit in one case, supporting future clinical trials of IA MSCs for ischemic stroke.
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