Application of Hepatocyte Growth Factor for Acute Spinal Cord Injury: The Road from Basic Studies to Human Treatment

International Journal of Molecular Sciences, 2019 · DOI: 10.3390/ijms20051054 · Published: February 28, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Hepatocyte growth factor (HGF) is a potent mitogen and neurotrophic factor. Introducing exogenous HGF into the spinal cord after injury promotes neuron and oligodendrocyte survival, angiogenesis, axonal regeneration, and functional recovery in rats. Studies in rodents have shown that HGF reduces astrocyte activation to decrease glial scar formation and exerts anti-inflammatory effects to reduce leukocyte infiltration after spinal cord injury (SCI). A phase I/II clinical trial of intrathecal recombinant human HGF (rhHGF) for patients with acute cervical SCI was conducted from June 2014 to May 2018.

Study Duration

Not specified

Participants

Rats, marmosets, and human patients in clinical trials

Evidence Level

Review of preclinical and clinical studies including phase I/II clinical trial

Key Findings

1
Exogenous HGF administration during the acute phase of SCI reduces astrocyte activation, decreasing glial scar formation and exerting anti-inflammatory effects.
2
Intrathecal infusion of recombinant human HGF (rhHGF) improves neurological hand function after cervical contusive SCI in common marmosets.
3
In aged mice with SCI, HGF promotes the survival and neuronal differentiation of grafted neural stem cells (NSCs), enhancing functional recovery.

Research Summary

This review summarizes the application of hepatocyte growth factor (HGF) for acute spinal cord injury (SCI), tracing the research journey from basic studies to human clinical trials. Preclinical studies in rodents and primates have demonstrated that HGF promotes neuroprotection, angiogenesis, axonal regrowth, and functional recovery after SCI. A phase I/II clinical trial of intrathecal recombinant human HGF (rhHGF) for acute cervical SCI patients was conducted, with promising results expected in the near future.

Practical Implications

Clinical Translation

The successful preclinical studies have paved the way for clinical trials, offering a potential new therapy for acute SCI in humans.

Combination Therapy

Combining HGF administration with neural stem cell transplantation may be a promising therapeutic strategy for SCI patients of all ages.

Therapeutic Time Window

Administering HGF during the acute phase of SCI is crucial for maximizing its therapeutic effects, suggesting the importance of early intervention.

Study Limitations

1
The efficacy and safety of methylprednisolone, the only neuroprotective therapy approved for acute SCI, remains controversial.
2
The therapeutic time window for treating acute SCI using neurotrophic factors might be longer for non-human primates than for rodents.
3
Intrathecal administration is more invasive than oral or intravenous administration, although it may be the best route for rhHGF delivery.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury