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Ryuji Kaji - One of the best experts on this subject based on the ideXlab platform.
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ultra high dose Methylcobalamin in amyotrophic lateral sclerosis a long term phase ii iii randomised controlled study
Journal of Neurology Neurosurgery and Psychiatry, 2019Co-Authors: Ryuji Kaji, Yasuo Iwasaki, Takashi Imai, Koichi Okamoto, Masanori Nakagawa, Yasuo Ohashi, Takao Takase, Takahisa Hanada, Hiroki Shimizu, Kunio TashiroAbstract:Objective To evaluate the efficacy and safety of intramuscular ultra-high-dose Methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). Methods 373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of Methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset). Results No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of Methylcobalamin-treated patients diagnosed and entered early (≤12 months’ duration) showed longer time intervals to the primary event (p Conclusion Although ultra-high-dose Methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. Trial registration number NCT00444613.
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JETALS: The Japanese Early-stage Trial of high dose Methylcobalamin for ALS
Brain and nerve = Shinkei kenkyu no shinpo, 2019Co-Authors: Yuishin Izumi, Satoshi Kuwabara, Ryosuke Oki, Ryuji KajiAbstract:High-dose Methylcobalamin was found to be a therapeutic candidate for amyotrophic lateral sclerosis (ALS) through clinical experience. Our previous study (E0302-J081-761) has suggested that high-dose Methylcobalamin (E0302) prolonged the overall survival and suppressed progression in ALS patients with a disease duration less than 12 months in, exploratory analyses. Therefore, we plan to conduct an investigator-initiated trial "The Japan Early-stage Trial of high dose Methylcobalamin for ALS (JETALS)" to evaluate the efficacy and safety of E0302 for ALS patients within 12 months from onset. JETALS is a prospective, multicenter, placebo-controlled, double-blind, randomized Phase III study, conducted at 25 tertiary neurology centers, and is funded by the Japan Agency for Medical Research and Development. A total of 128 patients were randomized at a 1:1 ratio to receive intramuscular injection with E0302 50 mg or placebo, twice a week for 16 weeks. The primary endpoint is changes in the ALS Functional Rating Scale (ALSFRS-R) total score at 16 weeks. The patient enrollment period is from November 2017 to September 2019, and the follow-up is scheduled to end in March 2020. If the results are positive, we intend to apply for E0302 approval for Methylcobalamin as a new drug for treating ALS.
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Neuroprotective effect of ultra-high dose Methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis.
Journal of the neurological sciences, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:High-dose of Methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose Methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS (Clinicaltrial.govNCT00444613). We attempted to study whether high-dose Methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. After initial diagnosis of the disease at the postnatal age of 3-4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg, n=10/group) or vehicle (n=10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n=5/group). In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of Methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Our results suggest that treatment with Methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used. Copyright © 2015. Published by Elsevier B.V.
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Neuroprotective effect of ultra-high dose Methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis.
Journal of the Neurological Sciences, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:Abstract Background High-dose of Methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose Methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS ( Clinicaltrial.gov NCT00444613 ). We attempted to study whether high-dose Methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. Methods After initial diagnosis of the disease at the postnatal age of 3–4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n = 5/group). Results In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of Methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Conclusion Our results suggest that treatment with Methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used.
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treatment with ultra high dose of Methylcobalamin attenuates motor dysfunction and neuropathological changes in wobbler mouse motor neuron disease p6 004
Neurology, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:OBJECTIVE: Recent studies reveal several common profiles of clinico-phenotypic, molecular and neuropathological changes between wobbler mice and amyotrophic lateral sclerosis (ALS) patients (Moser et al. Mol Genet Genomics 2013). We aimed to examine whether Methylcobalamin, a vitamin B12 analogue, ameliorates motor dysfunction and neuropathological findings in this ALS-like animal model. BACKGROUND: A previous double-blind controlled crossover trial of ultra-high dose Methylcobalamin suggested an increase of averaged compound muscle action potential amplitudes in ALS patients (Kaji et al, Muscle Nerve 1998). Currently, this larger-scale randomized double-blind trial is under analysis in Japanese ALS patients. DESIGN/METHODS: Immediately after the symptomatic onset at the postnatal age of 3-4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg) or vehicle, daily for 4 weeks by intraperitoneal administration in a blind fashion. Motor symptoms and neuropathological changes in the biceps muscle, the musculocutaneous nerve and the cervical (C5-6) cord were compared among three groups (n=10/group). Vitamin B12 levels of the serum, the skeletal muscle and the spinal cord were measured in vehicle- and two doses of Methylcobalamin-treated wobbler mice and untreated normal littermates (n=5/group). RESULTS: Higher dose of Methylcobalamin administration retarded progression of forelimb muscle weakness (P<0.01) and contracture (P<0.01), and suppressed denervation muscle atrophy (P<0.01) and axonal degeneration in the musculocutaneous nerve (P<0.05) compared to vehicle. The mean number of cervical motoneurons was increased approximately 20[percnt] in the high-dose Methylcobalamin group compared to vehicle. Vitamin B12 levels were elevated 5-6-fold in the serum, 3-5-fold in the biceps muscle and 3-4-fold in the spinal cord in higher dose of Methylcobalamin-treated wobbler mice compared to vehicle and normal littermates. CONCLUSIONS: The present study supported neuroprotective effects of ultra-high dose Methylcobalamin on denervating muscles and degenerating motor nerves in wobbler mouse motor neuron disease. This medication might have disease-delaying benefits in ALS patients. Study Supported by: None Disclosure: Dr. Ikeda has nothing to disclose. Dr. Iwasaki has nothing to disclose. Dr. Kaji has received research support from GlaxoSmithKline and Eisai Inc.
Hideki Yoshikawa - One of the best experts on this subject based on the ideXlab platform.
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Methylcobalamin increases erk1 2 and akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model
Experimental Neurology, 2010Co-Authors: Kiyoshi Okada, Hiroyuki Tanaka, Ko Temporin, Michio Okamoto, Yusuke Kuroda, Hisao Moritomo, Tsuyoshi Murase, Hideki YoshikawaAbstract:Methylcobalamin is a vitamin B12 analog and is necessary for the maintenance of the nervous system. Although some previous studies have referred to the effects of Methylcobalamin on neurons, the precise mechanism of this effect remains obscure. Here we show that Methylcobalamin at concentrations above 100 nM promotes neurite outgrowth and neuronal survival and that these effects are mediated by the methylation cycle, a metabolic pathway involving methylation reactions. We also demonstrate that Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle. In a rat sciatic nerve injury model, continuous administration of high doses of Methylcobalamin improves nerve regeneration and functional recovery. Therefore, Methylcobalamin may provide the basis for better treatments of nervous disorders through effective systemic or local delivery of high doses of Methylcobalamin to target organs.
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Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model.
Experimental neurology, 2010Co-Authors: Kiyoshi Okada, Hiroyuki Tanaka, Ko Temporin, Michio Okamoto, Yusuke Kuroda, Hisao Moritomo, Tsuyoshi Murase, Hideki YoshikawaAbstract:Methylcobalamin is a vitamin B12 analog and is necessary for the maintenance of the nervous system. Although some previous studies have referred to the effects of Methylcobalamin on neurons, the precise mechanism of this effect remains obscure. Here we show that Methylcobalamin at concentrations above 100 nM promotes neurite outgrowth and neuronal survival and that these effects are mediated by the methylation cycle, a metabolic pathway involving methylation reactions. We also demonstrate that Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle. In a rat sciatic nerve injury model, continuous administration of high doses of Methylcobalamin improves nerve regeneration and functional recovery. Therefore, Methylcobalamin may provide the basis for better treatments of nervous disorders through effective systemic or local delivery of high doses of Methylcobalamin to target organs.
Ken Ikeda - One of the best experts on this subject based on the ideXlab platform.
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Neuroprotective effect of ultra-high dose Methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis.
Journal of the neurological sciences, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:High-dose of Methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose Methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS (Clinicaltrial.govNCT00444613). We attempted to study whether high-dose Methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. After initial diagnosis of the disease at the postnatal age of 3-4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg, n=10/group) or vehicle (n=10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n=5/group). In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of Methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Our results suggest that treatment with Methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used. Copyright © 2015. Published by Elsevier B.V.
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Neuroprotective effect of ultra-high dose Methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis.
Journal of the Neurological Sciences, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:Abstract Background High-dose of Methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose Methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS ( Clinicaltrial.gov NCT00444613 ). We attempted to study whether high-dose Methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. Methods After initial diagnosis of the disease at the postnatal age of 3–4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n = 5/group). Results In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of Methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Conclusion Our results suggest that treatment with Methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used.
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treatment with ultra high dose of Methylcobalamin attenuates motor dysfunction and neuropathological changes in wobbler mouse motor neuron disease p6 004
Neurology, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:OBJECTIVE: Recent studies reveal several common profiles of clinico-phenotypic, molecular and neuropathological changes between wobbler mice and amyotrophic lateral sclerosis (ALS) patients (Moser et al. Mol Genet Genomics 2013). We aimed to examine whether Methylcobalamin, a vitamin B12 analogue, ameliorates motor dysfunction and neuropathological findings in this ALS-like animal model. BACKGROUND: A previous double-blind controlled crossover trial of ultra-high dose Methylcobalamin suggested an increase of averaged compound muscle action potential amplitudes in ALS patients (Kaji et al, Muscle Nerve 1998). Currently, this larger-scale randomized double-blind trial is under analysis in Japanese ALS patients. DESIGN/METHODS: Immediately after the symptomatic onset at the postnatal age of 3-4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg) or vehicle, daily for 4 weeks by intraperitoneal administration in a blind fashion. Motor symptoms and neuropathological changes in the biceps muscle, the musculocutaneous nerve and the cervical (C5-6) cord were compared among three groups (n=10/group). Vitamin B12 levels of the serum, the skeletal muscle and the spinal cord were measured in vehicle- and two doses of Methylcobalamin-treated wobbler mice and untreated normal littermates (n=5/group). RESULTS: Higher dose of Methylcobalamin administration retarded progression of forelimb muscle weakness (P<0.01) and contracture (P<0.01), and suppressed denervation muscle atrophy (P<0.01) and axonal degeneration in the musculocutaneous nerve (P<0.05) compared to vehicle. The mean number of cervical motoneurons was increased approximately 20[percnt] in the high-dose Methylcobalamin group compared to vehicle. Vitamin B12 levels were elevated 5-6-fold in the serum, 3-5-fold in the biceps muscle and 3-4-fold in the spinal cord in higher dose of Methylcobalamin-treated wobbler mice compared to vehicle and normal littermates. CONCLUSIONS: The present study supported neuroprotective effects of ultra-high dose Methylcobalamin on denervating muscles and degenerating motor nerves in wobbler mouse motor neuron disease. This medication might have disease-delaying benefits in ALS patients. Study Supported by: None Disclosure: Dr. Ikeda has nothing to disclose. Dr. Iwasaki has nothing to disclose. Dr. Kaji has received research support from GlaxoSmithKline and Eisai Inc.
Yasuo Iwasaki - One of the best experts on this subject based on the ideXlab platform.
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ultra high dose Methylcobalamin in amyotrophic lateral sclerosis a long term phase ii iii randomised controlled study
Journal of Neurology Neurosurgery and Psychiatry, 2019Co-Authors: Ryuji Kaji, Yasuo Iwasaki, Takashi Imai, Koichi Okamoto, Masanori Nakagawa, Yasuo Ohashi, Takao Takase, Takahisa Hanada, Hiroki Shimizu, Kunio TashiroAbstract:Objective To evaluate the efficacy and safety of intramuscular ultra-high-dose Methylcobalamin in patients with amyotrophic lateral sclerosis (ALS). Methods 373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of Methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset). Results No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of Methylcobalamin-treated patients diagnosed and entered early (≤12 months’ duration) showed longer time intervals to the primary event (p Conclusion Although ultra-high-dose Methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early. Trial registration number NCT00444613.
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Neuroprotective effect of ultra-high dose Methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis.
Journal of the neurological sciences, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:High-dose of Methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose Methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS (Clinicaltrial.govNCT00444613). We attempted to study whether high-dose Methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. After initial diagnosis of the disease at the postnatal age of 3-4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg, n=10/group) or vehicle (n=10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n=5/group). In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of Methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Our results suggest that treatment with Methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used. Copyright © 2015. Published by Elsevier B.V.
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Neuroprotective effect of ultra-high dose Methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis.
Journal of the Neurological Sciences, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:Abstract Background High-dose of Methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose Methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS ( Clinicaltrial.gov NCT00444613 ). We attempted to study whether high-dose Methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. Methods After initial diagnosis of the disease at the postnatal age of 3–4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n = 5/group). Results In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of Methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Conclusion Our results suggest that treatment with Methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used.
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treatment with ultra high dose of Methylcobalamin attenuates motor dysfunction and neuropathological changes in wobbler mouse motor neuron disease p6 004
Neurology, 2015Co-Authors: Ken Ikeda, Yasuo Iwasaki, Ryuji KajiAbstract:OBJECTIVE: Recent studies reveal several common profiles of clinico-phenotypic, molecular and neuropathological changes between wobbler mice and amyotrophic lateral sclerosis (ALS) patients (Moser et al. Mol Genet Genomics 2013). We aimed to examine whether Methylcobalamin, a vitamin B12 analogue, ameliorates motor dysfunction and neuropathological findings in this ALS-like animal model. BACKGROUND: A previous double-blind controlled crossover trial of ultra-high dose Methylcobalamin suggested an increase of averaged compound muscle action potential amplitudes in ALS patients (Kaji et al, Muscle Nerve 1998). Currently, this larger-scale randomized double-blind trial is under analysis in Japanese ALS patients. DESIGN/METHODS: Immediately after the symptomatic onset at the postnatal age of 3-4 weeks, wobbler mice received Methylcobalamin (3 or 30 mg/kg) or vehicle, daily for 4 weeks by intraperitoneal administration in a blind fashion. Motor symptoms and neuropathological changes in the biceps muscle, the musculocutaneous nerve and the cervical (C5-6) cord were compared among three groups (n=10/group). Vitamin B12 levels of the serum, the skeletal muscle and the spinal cord were measured in vehicle- and two doses of Methylcobalamin-treated wobbler mice and untreated normal littermates (n=5/group). RESULTS: Higher dose of Methylcobalamin administration retarded progression of forelimb muscle weakness (P<0.01) and contracture (P<0.01), and suppressed denervation muscle atrophy (P<0.01) and axonal degeneration in the musculocutaneous nerve (P<0.05) compared to vehicle. The mean number of cervical motoneurons was increased approximately 20[percnt] in the high-dose Methylcobalamin group compared to vehicle. Vitamin B12 levels were elevated 5-6-fold in the serum, 3-5-fold in the biceps muscle and 3-4-fold in the spinal cord in higher dose of Methylcobalamin-treated wobbler mice compared to vehicle and normal littermates. CONCLUSIONS: The present study supported neuroprotective effects of ultra-high dose Methylcobalamin on denervating muscles and degenerating motor nerves in wobbler mouse motor neuron disease. This medication might have disease-delaying benefits in ALS patients. Study Supported by: None Disclosure: Dr. Ikeda has nothing to disclose. Dr. Iwasaki has nothing to disclose. Dr. Kaji has received research support from GlaxoSmithKline and Eisai Inc.
Kiyoshi Okada - One of the best experts on this subject based on the ideXlab platform.
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Methylcobalamin increases erk1 2 and akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model
Experimental Neurology, 2010Co-Authors: Kiyoshi Okada, Hiroyuki Tanaka, Ko Temporin, Michio Okamoto, Yusuke Kuroda, Hisao Moritomo, Tsuyoshi Murase, Hideki YoshikawaAbstract:Methylcobalamin is a vitamin B12 analog and is necessary for the maintenance of the nervous system. Although some previous studies have referred to the effects of Methylcobalamin on neurons, the precise mechanism of this effect remains obscure. Here we show that Methylcobalamin at concentrations above 100 nM promotes neurite outgrowth and neuronal survival and that these effects are mediated by the methylation cycle, a metabolic pathway involving methylation reactions. We also demonstrate that Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle. In a rat sciatic nerve injury model, continuous administration of high doses of Methylcobalamin improves nerve regeneration and functional recovery. Therefore, Methylcobalamin may provide the basis for better treatments of nervous disorders through effective systemic or local delivery of high doses of Methylcobalamin to target organs.
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Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model.
Experimental neurology, 2010Co-Authors: Kiyoshi Okada, Hiroyuki Tanaka, Ko Temporin, Michio Okamoto, Yusuke Kuroda, Hisao Moritomo, Tsuyoshi Murase, Hideki YoshikawaAbstract:Methylcobalamin is a vitamin B12 analog and is necessary for the maintenance of the nervous system. Although some previous studies have referred to the effects of Methylcobalamin on neurons, the precise mechanism of this effect remains obscure. Here we show that Methylcobalamin at concentrations above 100 nM promotes neurite outgrowth and neuronal survival and that these effects are mediated by the methylation cycle, a metabolic pathway involving methylation reactions. We also demonstrate that Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle. In a rat sciatic nerve injury model, continuous administration of high doses of Methylcobalamin improves nerve regeneration and functional recovery. Therefore, Methylcobalamin may provide the basis for better treatments of nervous disorders through effective systemic or local delivery of high doses of Methylcobalamin to target organs.
