Background: Cell therapy is promising in pre-clinical studies of global ischemia. The aim of this pilot study is to describe the first intra-arterial (IA) delivery of bone marrow derived ALD-401 cells in a persistent vegetative state (PVS) patient in the U.S. & findings on MRI Diffusion Tensor Imaging (DTI) and Diffusion Tensor Tractography (DTT).
Material: A 51-yr. woman developed PVS due to cardiac arrest. At 2 years post PVS state, experimental cell therapy was requested by the family. The FDA approved a one-time compassionate use IA delivery of ALD-401 cells. Bone marrow harvest from the patient, followed by processing with flow cytometry was completed to separate ALD-401 cells. Intra-arterial infusion of cells was done bilaterally into each supra-clinoid carotid. Post-infusion neurological assessments- National Institute of Health Stroke Scale (NIHSS), JFKr coma recovery scale, brainstem reflexes, modified Rankin Scores (mRS) and MRI DTI imaging were collected at 1-, 3-, 6-, 9-mo & 1 year
Result: The patient had no adverse events peri-operatively. Over 1-year follow-up the patient had 1 hospitalization for UTI and postmenopausal bleeding. No other adverse events occurred. Minor clinical improvement was shown on assessment scales above. However, DTI-DTT analysis of Fractional Anisotropy (FA) showed improvement in the FA and ADC of white matter tracts starting 7 months post injection for the Cortical Spinal Tract (CST) and starting 4 months post injection for the Corpus Callosum (CC) months (see figure). Diffusion Tensor Tractography also showed qualitative improvement in organization and caliber of CC & CST over follow-up post intervention (see figure)
Conclusion: Assessing minor neurological improvements in this severe PVS patient remains challenging; DTI-DTT MRI imaging detects changes in white mater tracts that could serve as biomarkers for recovery. Further follow-up clinical assessments and imaging will continue in this patient to define further recovery.