| Budget Amount *help |
¥3,340,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Since amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease with unknown etiology, the effective new therapy establishment is strongly desired. In this study, therefore, we have established the new ALS therapy by midkine (MK), which is one of nerve growth factors.
For the establishment of the new ALS therapy by midkine, for the first time, we have produced two types of MK antibodies: one is a monoclonal antibody which recognizes only human MK and the other is a polyclonal antibody which recognizes MK among human, mouse, and rat. Second, we have analyzed 40 cases of human sporadic ALS and 5 cases of familial ALS with mutant SOD1 of two families, in addition to 3 lines of ALS animal models: G1 H-G93A mice, G93A rats, and H46R rats. In not only human autopsy cases but also ALS animal models, some motor neurons express MK in order to survive again ALS stress. Third we have produced MK overexpressing transgenic (MK-Tg) mice, which strongly express MK in motor neurons. Fourth, we have succeeded in producing mutation SOD1-MK overexpressing double transgenic (MK-ALS Tg) mice. MK-ALS Tg mice have shown a longer survival in comparison with ALS Tg mice clinically. In MK-ALS Tg mice, MK-histopathologically-overexpressing motor neurons have longer survived, compared with motor neurons without expression MK.
This study results that MK protects motor neuron death caused by ALS, and provides a new ALS therapy by MK.
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