Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunological capability is to a substantial extent genetically determined. Because genetic linkage exists between histocompatibility gene loci and certain immune response gene loci, histocompatibility specificities can serve as indicators for the presence of particular inherited immunological traits. In man, certain HLA antigens seem to be associated with immunogenetic traits which result in altered susceptibility to disease with known or suspected viral or autoimmune etiologies. We have found an association between HLA-A3 and "classic" cases of ALS. The A3 antigen was present in 49% of these cases, but not in the more chronic or benign form of the disease. Five out of six "benign" cases carried HLA-B12, suggesting perhaps the presence of a trait conferring resistance to the disease. Epidemiological surveys provide evidence both for and against a correlation between the incidence of ALS and that of HLA-A3 in various population groups. Because of the multiplicity of immune response genes, susceptibility or resistance to ALS in different populations may depend on different immune response genes. The association of a disease with selected HLA antigens or phenotypes might be suggestive of a viral-allergic etiology. Evidence that bears on this hypothesis has been reviewed.
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PMID:Immunogenetics and amyotrophic lateral sclerosis. 102 69

To evaluate the current nutrition therapy for the patients of amyotrophic lateral sclerosis (ALS) in Japan, we sent questionnaires to 53 Japanese national sanatoriums (hospitals) and were able to collect replies from 42 institutes. In these replies, information on 466 patients (262 inpatients and 204 outpatients) was reported, accounting for about 10% of all Japanese ALS patients. Patients who ate orally were more frequent (p < 0.001, chi 2 test) in the outpatients (76.0%) than in the inpatients (39.7%). When the subjects were limited to non-orally nourished cases, gastrostomy was more frequently performed (p < 0.05, chi 2 test) in the outpatients (49%) than in the inpatients (29.1%), but no significant differences were observed between the above two groups as to the quantity of daily caloric intake; the mode was 1000-1200 Cal. About a quarter of non-orally nourished patients received supplemental sodium chloride, and fewer were supplemented copper and/or zinc. The consent of the patients as well as the clinical findings weighed heavily in the determination of the feeding route. Most physicians were disinclined to encourage tube feeding in the early stage of dysphagia, but were supportive of the operation of percutaneous endoscopic gastrostomy when non-oral nutrition therapy became necessary. Although the efficacy of vitamins for ALS has not been proved, 45 of 58 physicians agreed to subscribe vitamins to their patients, especially vitamin B12, E and C.
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PMID:[A survey of current nutrition therapy for the ALS patients in Japanese national sanatoriums]. 1133 87

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons. Weakness may begin in the legs, hands, proximal arms, or pharynx. The course is relentless and progressive without remissions, relapses, or even stable plateaus. There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect on cultured cortical neurons against glutamate-induced cytotoxicity. We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated. Larger-scale randomized double blind trial was started in Japan in order to evaluate the long-term efficacy and the safety of ultra-high-dose methylcobalamin for sporadic or familial cases of ALS.
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PMID:[Clinical trials of ultra-high-dose methylcobalamin in ALS]. 1796 54

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by selective degeneration of motor neurons. Mutations in copper/zinc superoxide dismutase (SOD1) account for 20% cases of familial ALS (fALS), but the underlying pathogenetic mechanisms are largely unknown. Using SOD1(G93A) mice model of ALS, we demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine (Hcy). To investigate whether Hcy-lowering therapy is beneficial to this disease, we applied folic acid (FA) and vitamin B12 which are important factors involved in the Hcy metabolism to assess the neuroprotective effect of FA and B12 in the SOD1(G93A) mice. Our results showed FA or FA+B12 treatment significantly delayed the disease onset and prolonged the lifespan, accompanied by the significant reduction of motor neuron loss. Furthermore, we found that FA or FA+B12 treatment significantly attenuated the plasma Hcy level, suppressed the activation of microglia and astrocytes, and inhibited the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in spinal cord. Moreover, FA or FA+B12 treatment decreased the levels of cleaved caspase-3 and poly(ADP-ribose)polymerase (PARP) but up-regulated the level of anti-apoptotic protein Bcl-2. However, B12 treatment alone did not show any significant benefit to this disease. These results provide evidence to demonstrate that elevated Hcy is involved in the pathogenesis of fALS and FA therapy may have therapeutic potential for the treatment of the disease.
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PMID:Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice. 1843 68

Methylcobalamin is a vitamin B12 analog that is necessary for nervous system maintenance. Although methylcobalamin has some positive effects on peripheral nervous system disorders, the mechanism through which it affects neurons are not entirely known. Recent studies have revealed its intracellular signaling pathway and some of its molecular actions on neurons. In this article, I review interactions between methylcobalamin and neurons that have been revealed through in vitro studies, in vivo studies, and clinical use. Methylcobalamin participates in nervous system maintenance through several mechanisms. Methylcobalamin is an active form of vitamin B12, and a coenzyme of methionine synthase, which is required for DNA and protein methylation. In addition, methylcobalamin facilitates neurite outgrowth and inhibits neural apoptosis through the Erk1/2 and Akt signaling pathways. Treatment with high doses of methylcobalamin ameliorates symptoms and negative electrophysiological findings in animal models of peripheral nerve neuropathy and in patients with carpal tunnel syndrome and amyotrophic lateral sclerosis. Thus, high-dose methylcobalamin has great potential for treating nervous system disorders. Further investigations with methylcobalamin may help elucidate its mechanisms of action, which may further enable us to treat many nervous system disorders.
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PMID:[Old or new medicine? Vitamin B12 and peripheral nerve neuropathy]. 2401 44

The current study for the first time is devoted to the application of whole space genetic algorithm-radial basis function network (wsGA-RBFN) method to determine the content micro minerals of Zn(2+), Fe(2+), Co(2+) and Cu(2+) based on their complexes formation with methylthymol blue (MTB) spectrophotometrically in various pharmaceutical products and vegetable samples. Advantage of wsGA-RBFN compared to GA-RBFN is that centers can be located in any point of the samples spaces. Initially, the parameters controlling behavior of the system were investigated and optimum conditions were selected. Then, an exploratory analysis of complex systems was carried out by chemometrics approaches such as SVD, EFA, MCR-ALS and RAFA. The optimal parameters and conditions for constructing the proposed model of wsGA-RBFN were obtained from processing the data set of synthetic samples. Finally, wsGA-RBFN was successfully applied to the simultaneous determination of Zn(2+), Fe(2+), Co(2+) and Cu(2+) in tomato, white cabbage, red cabbage and lettuce and pharmaceutical products included iron, zinc, multi complete and B12 ampoule.
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PMID:Application of a new version of GA-RBF neural network for simultaneous spectrophotometric determination of Zn(II), Fe(II), Co(II) and Cu(II) in real samples: An exploratory study of their complexation abilities toward MTB. 2759 91

Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disorder that causes motor dysfunction. Treatments and drugs that slow progression of ALS have garnered great interest. In the present study, we show that the vitamin B12 analog methylcobalamin (MBL) effectively and dose dependently prevented embryonic stem cell-derived motor neuron death induced by cocultivation with astrocytes expressing mutant human superoxide dismutase-1 (G93A). Moreover, cotreatment of MBL with a conventional ALS drug, riluzole, further enhanced survival of motor neurons in this in-vitro ALS model. Our results show the potential use of MBL as a treatment for ALS and suggest a possible combination therapy strategy with other types of approved ALS drugs.
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PMID:Methylcobalamin prevents mutant superoxide dismutase-1-induced motor neuron death in vitro. 2792 48