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Updated: Jun 25, 2026
11:12
Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells
Published on: October 4, 2017
[Amyotrophic lateral sclerosis with the SOD1 mutations]
Masashi Aoki1, Hitoshi Warita, Yasuto Itoyama
1Department of Neurology, Tohoku University School of Medicine, Tohoku University Hospital ALS Center.
Rinsho Shinkeigaku = Clinical Neurology
|February 10, 2009
Summary
Mutations in Cu/Zn superoxide dismutase (SOD1) cause familial amyotrophic lateral sclerosis (ALS). Hepatocyte growth factor (HGF) treatment in a rat model significantly slowed motor neuron degeneration and disease progression, suggesting therapeutic potential for ALS.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Mutations in Cu/Zn superoxide dismutase (SOD1) are linked to familial amyotrophic lateral sclerosis (ALS).
- Different SOD1 mutations result in variable disease onset and duration, suggesting mutation-specific protein toxicity.
- A novel rat model expressing human SOD1 transgenes with ALS-associated mutations (G93A, H46R) exhibits motor neuron degeneration and paralysis.
Purpose of the Study:
- To investigate the neuroprotective effects and therapeutic potential of hepatocyte growth factor (HGF) in a rat model of familial ALS.
- To evaluate the efficacy of continuous intrathecal administration of human recombinant HGF (hrHGF) in attenuating motor neuron degeneration and prolonging disease duration.
Main Methods:
- Developed transgenic rats expressing human SOD1 with G93A and H46R mutations.
- Administered hrHGF via continuous intrathecal delivery to G93A transgenic rats starting at symptom onset for 4 weeks.
- Assessed motor neuron degeneration and disease progression in treated and control rats.
Main Results:
- Intrathecal administration of hrHGF significantly attenuated motor neuron degeneration in G93A transgenic rats.
- hrHGF treatment prolonged the disease duration by 63% in the G93A transgenic rat model.
- The rat model's size facilitates studies on spinal fluid and spinal cord interventions.
Conclusions:
- Continuous intrathecal administration of hrHGF demonstrates therapeutic efficacy in a rat model of SOD1-linked ALS.
- HGF shows promise as a neuroprotective agent for motor neurons in ALS.
- These findings support further clinical trials for ALS using continuous intrathecal HGF delivery.
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