Publication Date:
2011-11-18
Description:
Abstract 4393 Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by loss of motoneurons (mns), and it has no cure. Cell therapy has neurotrophic effects in animal models and has been proposed as a disease-modifying treatment. Our aim was twofold: firstly, to assess the safety of intraspinal infusion of bone marrow mononuclear cells (BMNC) and, ultimately, to look for histopathological signs of cellular neurotrophism. Methods: We conducted an open single arm phase I trial. After six months observation, autologous BMNC were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC) and ALS-FRS, MRC and Norris scales were assessed six and three months prior to the transplant and quarterly afterwards for one year. Pathological studies were performed in case of death. Findings: Eleven patients were included. We did not observe any severe transplant-related adverse event but there were 43 non-severe events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were CTCAE grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris or MRC scales was observed. Four patients died on days 359, 378, 808 and 1058 postransplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of montoneurons in the treated compared to the untreated segments (4.2+/−0.8 mns/section and 0.9+/−0.3 mns/section, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. Interpretation: This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence of their neurotrophic activity. Disclosures: No relevant conflicts of interest to declare.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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