The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs 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), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events 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 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity.

In conclusion, our results suggest that liver transplant may be useful in the treatment of certain cases of familial amyloidotic polyneuropathy to stop the neurological deterioration of the patients and to avoid the fatal end of the disease.

Intramuscular Stem Cells in ALS justify exploring the efficacy of this procedure in further patients and other muscles, through Phase II trials.Clinical Trial Registration www.clinicaltrials.gov (identifier NCT02286011); EudraCT number 2011-004801-25.

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Familial amyloidotic polyneuropathy type I (FAP I) is a hereditary systemic amyloidosis usually involving the peripheral nervous system. In this paper we report our experience regarding the survival and the evolution of the sensory motor syndrome of the extremities and autonomic dysfunction in four siblings with the Ala-71 variant who were treated by liver transplantation (LT). The four siblings are alive 2-5 years after LT. After the operation, the seriated determinations of TTR-Ala-71 variant showed a constant decrease in serum levels in all cases. Our results support the proposal that LT should be indicated especially in forms with early clinical onset (3rd and 4th decades) and rapid progress to stop the neurological deterioration of the patients.