[Hepatocyte growth factor therapy for amyotrophic lateral sclerosis]

Area of Science:

• Neuroscience
• Genetics
• Regenerative Medicine

Background:

• Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons.
• Mutations in the superoxide dismutase 1 (SOD1) gene account for approximately 20% of familial ALS cases.
• A novel rat model expressing human SOD1 mutations was developed to study ALS pathogenesis and test therapies.

Purpose of the Study:

• To evaluate the therapeutic potential of hepatocyte growth factor (HGF) for ALS.
• To investigate the efficacy of intrathecal administration of human recombinant HGF (hrHGF) in a rat model of SOD1-linked ALS.
• To assess the functional recovery effects of hrHGF in a primate model of spinal cord injury.

Main Methods:

• Transgenic rats expressing human SOD1 mutations were treated with continuous intrathecal hrHGF for 4 weeks starting at disease onset.
• Motor neuron degeneration and disease duration were assessed in treated and control rats.
• hrHGF was administered intrathecally to common marmosets following induced cervical spinal cord injury to evaluate functional recovery.

Main Results:

• Intrathecal hrHGF administration significantly attenuated motor neuron degeneration in SOD1-mutant rats.
• The duration of the disease was extended by 62.7% in hrHGF-treated rats compared to controls.
• Intrathecal hrHGF administration promoted functional recovery in marmosets with spinal cord injury.

Conclusions:

• Continuous intrathecal administration of hrHGF is a potentially effective therapeutic strategy for ALS.
• HGF demonstrates neuroprotective effects on motor neurons and promotes functional recovery in neurological injury models.
• This study supports the development of HGF-based therapies for ALS and other motor neuron diseases.