Stem cell treatment in Amyotrophic Lateral Sclerosis

Department of Neurology, Azienda Ospedaliera, Eastern Piedmont University of Novara, Novara, Italy.
Journal of the Neurological Sciences (Impact Factor: 2.47). 03/2008; 265(1-2):78-83. DOI: 10.1016/j.jns.2007.05.016
Source: PubMed


Amyotrophic Lateral Sclerosis is a progressive fatal neurodegenerative disease that targets motor neurons. Its origin is unknown but a main role of reactive astrogliosis and microglia activation in the pathogenesis has been recently demonstrated. Surrounding neurons with healthy adjoining cells completely stops motor neuron death in some cases. Hence stem cell transplantation might represent a promising therapeutic strategy. In this study MSCs were isolated from bone marrow of 9 patients with definite ALS. Growth kinetics, immunophenotype, telomere length and karyotype were evaluated during in vitro expansion. No significant differences between donors or patients were observed. The patients received intraspinal injections of autologous MSCs at the thoracic level and monitored for 4 years. No significant acute or late side effects were evidenced. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. Four patients show a significant slowing down of the linear decline of the forced vital capacity and of the ALS-FRS score. Our results seem to demonstrate that MSCs represent a good chance for stem cell cell-based therapy in ALS and that intraspinal injection of MSCs is safe also in the long term. A new phase 1 study is carried out to verify these data in a larger number of patients.

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Available from: Letizia Mazzini
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    • "These include induction of neuronal plasticity and remodeling of the brain in multiple sclerosis (MS) [84] [85] [86] and tissue regeneration e.g. in spinal cord injury [84] [87]. Similar improvement by MSC treatment was detected in animal models of stroke [88], Amyotrophic lateral sclerosis (ALS) [89], Huntington's disease [90] and Parkinson's disease [91] [92]. "
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    ABSTRACT: Recent studies of Autism Spectrum Disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.
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    • "Furthermore, mesenchymal stem cells are capable of differentiating into neurons and astrocytes in vitro and in vivo[36]. Recently, mesenchymal stem cell injection has shown promise for amyotrophic lateral sclerosis treatment in humans[37]. They are able to improve neurological deficits and promote the restoration of functional synaptic transmission when transplanted into animal models of neurological disorders[38]. "
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    ABSTRACT: We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was significantly enhanced in the model group. After 8 weeks, the number of horseradish peroxidase-labeled nerve fibers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and significantly higher than in the model group. The newly formed nerve fibers and myelinated nerve fibers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group.
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    • "There have been several early-phase clinical trials of the treatment of ALS with hMSCs [51,56,57,66]. Bone marrow cells (BMCs), which may consist of mesenchymal and hematopoietic stem cell types, have also been investigated for cell therapy in ALS [52,53,67]. "
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the neuromuscular system and does not have a known singular cause. Genetic mutations, extracellular factors, non-neuronal support cells, and the immune system have all been shown to play varied roles in clinical and pathological disease progression. The therapeutic plasticity of mesenchymal stem cells (MSCs) may be well matched to this complex disease pathology, making MSCs strong candidates for cellular therapy in ALS. In this review, we summarize a variety of explored mechanisms by which MSCs play a role in ALS progression, including neuronal and non-neuronal cell replacement, trophic factor delivery, and modulation of the immune system. Currently relevant techniques for applying MSC therapy in ALS are discussed, focusing in particular on delivery route and cell source. We include examples from in vitro, preclinical, and clinical investigations to elucidate the remaining progress that must be made to understand and apply MSCs as a treatment for ALS.
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