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Aims: Mutations in DNA/RNA‐binding factor (fused‐in‐sarcoma) FUS and superoxide dismutase‐1 (SOD‐1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD‐1‐G93A (SOD‐1) and new FUS[1‐359]‐transgenic (FUS‐tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti‐inflammatory treatments were investigated using these mutants. Methods: FUS‐tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti‐inflammatory drug a selective blocker of cyclooxygenase‐2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro‐Cells (a preparation of 1.39 × 106 mesenchymal and hemopoietic human stem cells, containing 5 × 105 of CD34+ cells), which showed anti‐inflammatory properties. SOD‐1 mice received i.c.v.‐administration of Neuro‐Cells or vehicle. Results: All FUS‐tg‐treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS‐tg‐vehicle‐treated mice. Neuro‐Cell‐treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib‐FUS‐tg‐treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium‐binding adapter molecule‐1 (Iba‐1), and glycogen‐synthase‐kinase‐3ß (GSK‐3ß). The Neuro‐Cells‐treated‐SOD‐1 mice showed better motor functions than vehicle‐treated‐SOD‐1 group. Conclusion: The neuropathology in FUS‐tg mice is sensitive to standard ALS treatments and Neuro‐Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. [ABSTRACT FROM AUTHOR]