PMC:6141714 / 134501-137087 JSONTXT

{"project":"MyTest","denotations":[{"id":"30254638-10496275-35421876","span":{"begin":492,"end":495},"obj":"10496275"},{"id":"30254638-15589308-35421877","span":{"begin":781,"end":784},"obj":"15589308"},{"id":"30254638-16831965-35421878","span":{"begin":1027,"end":1030},"obj":"16831965"},{"id":"30254638-10496275-35421879","span":{"begin":1147,"end":1150},"obj":"10496275"},{"id":"30254638-26807122-35421880","span":{"begin":1236,"end":1239},"obj":"26807122"},{"id":"30254638-10496275-35421881","span":{"begin":1804,"end":1807},"obj":"10496275"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Neuromyelitis optica is an inflammatory, demyelinating, and autoimmune disease of the central nervous system, which selectively affects the spinal cord and optic nerves, simultaneously or sequentially. Symptoms of neuromyelitis optica include loss of vision, sensitivity changes, muscle weakness, spasticity, incoordination, ataxia, urinary and fecal incontinence, and autonomic dysfunctions in parts of the trunk and limbs supplied by nerves coming out of the spine below the spinal lesion (215). Clinical and serological evidence of autoimmunity associated with B cells has been observed in patients with neuromyelitis optica, in whom demyelinating lesions exhibit perivascular immunoglobulin deposition, local activation of the complement cascade and eosinophilic infiltration (216). Other mechanisms involved in this humoral response are the secretion of IL-2, anti-myelin autoantibodies, oligodendrocyte-associated anti-glycoprotein autoantibodies, and IgG autoantibodies against the astroglial water channel aquaporin-4 (217). In general, neuromyelitis optica attacks are more severe than those of multiple sclerosis and are commonly fatal (215). The treatment of neuromyelitisoptica was carried out with hMSCs in only one study (149). This study was conducted in humans and used bone marrow-derived hMSCs for the treatment of the autoimmune disease. The study selected in this systematic review was a single case report and used the healing of pressure ulcers, the improvement of disability, the ability to walk, and the occurrence of relapse and adverse events as the primary endpoints that were used in order to assess the efficacy of hMSCs administration for the treatment of neuromyelitis optica. Because the occurrence of attacks is the main cause of neuromyelitis optica-related disability (215), we propose that the frequency and severity of attacks should be considered as the most appropriate primary endpoints in neuromyelitis optica clinical trials. In addition, exploratory endpoints such the serum levels of autoantibodies and inflammatory cytokines can be used to determinate what are the mechanisms used by the hMSCs administered to inhibit the occurrence of the pathological process. In the study selected, a reduction in both the severity and in the clinical parameters of the disease was observed following the administration of hMSCs. Table 7 summarizes the methodology employed and the results obtained in the studies selected in this systematic review regarding the effects of the administration of hMSCs for the treatment of autoimmune neurologic disorders."}

{"project":"2_test","denotations":[{"id":"30254638-10496275-35421876","span":{"begin":492,"end":495},"obj":"10496275"},{"id":"30254638-15589308-35421877","span":{"begin":781,"end":784},"obj":"15589308"},{"id":"30254638-16831965-35421878","span":{"begin":1027,"end":1030},"obj":"16831965"},{"id":"30254638-10496275-35421879","span":{"begin":1147,"end":1150},"obj":"10496275"},{"id":"30254638-26807122-35421880","span":{"begin":1236,"end":1239},"obj":"26807122"},{"id":"30254638-10496275-35421881","span":{"begin":1804,"end":1807},"obj":"10496275"}],"text":"Neuromyelitis optica is an inflammatory, demyelinating, and autoimmune disease of the central nervous system, which selectively affects the spinal cord and optic nerves, simultaneously or sequentially. Symptoms of neuromyelitis optica include loss of vision, sensitivity changes, muscle weakness, spasticity, incoordination, ataxia, urinary and fecal incontinence, and autonomic dysfunctions in parts of the trunk and limbs supplied by nerves coming out of the spine below the spinal lesion (215). Clinical and serological evidence of autoimmunity associated with B cells has been observed in patients with neuromyelitis optica, in whom demyelinating lesions exhibit perivascular immunoglobulin deposition, local activation of the complement cascade and eosinophilic infiltration (216). Other mechanisms involved in this humoral response are the secretion of IL-2, anti-myelin autoantibodies, oligodendrocyte-associated anti-glycoprotein autoantibodies, and IgG autoantibodies against the astroglial water channel aquaporin-4 (217). In general, neuromyelitis optica attacks are more severe than those of multiple sclerosis and are commonly fatal (215). The treatment of neuromyelitisoptica was carried out with hMSCs in only one study (149). This study was conducted in humans and used bone marrow-derived hMSCs for the treatment of the autoimmune disease. The study selected in this systematic review was a single case report and used the healing of pressure ulcers, the improvement of disability, the ability to walk, and the occurrence of relapse and adverse events as the primary endpoints that were used in order to assess the efficacy of hMSCs administration for the treatment of neuromyelitis optica. Because the occurrence of attacks is the main cause of neuromyelitis optica-related disability (215), we propose that the frequency and severity of attacks should be considered as the most appropriate primary endpoints in neuromyelitis optica clinical trials. In addition, exploratory endpoints such the serum levels of autoantibodies and inflammatory cytokines can be used to determinate what are the mechanisms used by the hMSCs administered to inhibit the occurrence of the pathological process. In the study selected, a reduction in both the severity and in the clinical parameters of the disease was observed following the administration of hMSCs. Table 7 summarizes the methodology employed and the results obtained in the studies selected in this systematic review regarding the effects of the administration of hMSCs for the treatment of autoimmune neurologic disorders."}