Functional Status, Quality of Life and Survival After Repeated Intrathecal Administration of Autologous Lineage-Negative Cells in Amyotrophic Lateral Sclerosis

Abstract

Background/Objectives: Adjuvant cell-based strategies are still being explored in amyotrophic lateral sclerosis (ALS). Materials and Methods: In this open-label, single-arm study of intrathecal autologous bone marrow-derived lineage-negative (LIN−) cells, we report functional status, quality of life, and survival after three administrations at six-week intervals. A total of 45 patients with sporadic ALS were qualified: 42 received all three administrations and 23 completed the 24-week assessment schedule, while 19 stopped attending because of deterioration. Results: In the 23 completers, Norris scale scores were stable until week 13 and then declined (p = 0.00004), and the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSAQ-40) followed the same pattern (p = 0.0019), whereas the ALS Functional Rating Scale—Revised (ALSFRS-R) declined at a constant 0.5 points per month. In all 42 treated patients the Norris score fell during treatment (0.95 points per month; 95% CI 0.52–1.38), so the plateau was confined to completers, who had milder baseline disease. Dose-related differences in quality of life were confounded by baseline imbalance; survival analyses were exploratory. Cell number did not correlate with cerebrospinal fluid brain-derived neurotrophic factor (BDNF) after the third administration in the 39 patients with paired samples (ρ = 0.14). No adverse event was recorded in 126 procedures, but harms were not graded systematically. Conclusions: These exploratory findings do not demonstrate efficacy; a sham-controlled trial with blinded raters is required.