Development of a novel therapeutic approach for ALS using anti-TNF antibody

使用抗 TNF 抗体开发 ALS 新型治疗方法

• 批准号: 23659458
• 负责人: KAJI Ryuji
• 金额: $ 2.25万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659458/
• 关键词: ＴＮＦα; ＡＬＳ; ＳＯＤ１; adalizumab; ALS; therapy; SOD1 tansgenic mouse

Mouse anti-TNF alpha antibody was intraperitoneally administered to SOD1 mice, which are widely used for animal model for amyotrophic lateral sclerosis. We physiologically and pathologically evaluated the efficacy of the therapy or suppression of disease progression. No significant result was obtained in physiological evaluations, including life span, body weight and motor functions. However, pathological examination revealed partial ameliorative response, including the numbers of survival motor neurons and the reactive gliosis. These results further supported involvement of neuroinflammation in motor neuron death by mutant SOD1 probably at the end stage. Evaluation of the downstream cascades, such as NF kappa, JNK-AP-1 and caspase 3, is necessary to optimize the therapy using the anti-TNF alpha antibody.

将小鼠抗-TNFα抗体腹膜内疗法给SOD1小鼠，该抗体被广泛用于动物模型用于肌萎缩性侧面硬化症。我们在生理和病理上评估了疾病进展的治疗或抑制的功效。生理评估，包括寿命，体重和运动功能，没有获得显着结果。然而，病理检查显示部分改善反应，包括生存运动神经元的数量和反应性神经胶质病。这些结果进一步支持了突变体SOD1可能在末期引起神经炎症在运动神经元死亡中的参与。必须评估下游级联反应，例如NF Kappa，JNK-AP-1和caspase 3，对于使用抗TNF Alpha抗体优化治疗是必要的。

项目成果

神経内科

神经病学

• 发表时间: 2011
• 作者: 井口正寛;松田憲之;田中啓二
• 通讯作者: 田中啓二

Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy

• DOI: 10.1136/jnnp-2011-300783
• 发表时间: 2011-08
• 期刊: Journal of Neurology, Neurosurgery & Psychiatry
• 作者: K. Fujita;Mari Yoshida;W. Sako;Kouji Maeda;Y. Hashizume;S. Goto;G. Sobue;Y. Izumi;R. Kaji

Electrophysiological diagnosis of ALS

ALS的电生理诊断

• 发表时间: 2011
• 作者: Noda Y;Asada M;Kubota M;Maesako M;Watanabe K;Uemura M;Kihara T;Shimohama S;Takahashi R;Kinoshita A;Uemura K;Kaji R
• 通讯作者: Kaji R

TFG 変異による運動ニューロン死のメカニズム

TFG突变导致运动神经元死亡的机制

• 发表时间: 2013
• 作者: 瓦井俊孝;森田光哉;森垣龍馬;藤田浩司;野寺裕之;和泉唯信;後藤惠;中野今治;梶龍兒
• 通讯作者: 梶龍兒

Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis

• DOI: 10.1016/j.neurobiolaging.2012.05.011
• 发表时间: 2012-10-01
• 期刊: NEUROBIOLOGY OF AGING
• 影响因子: 4.2
• 作者: Ogaki, Kotaro;Li, Yuanzhe;Sobue, Gen
• 通讯作者: Sobue, Gen