TABLE 2.
Hepatocyte growth factor gene transfer in animal models of neurological diseases.
| Disease application | Methods | Year | Animal model | Outcomes | References |
| ALS | Generation of HGF transgenic mice (SOD1-G93A) | 2002 | Mouse | Inhibition of caspase-1 induced apoptosis and reduction of iNOS in motor neurons; protection from excitotoxic death induced by glutamate; EAAT2 protein enhancement in astrocytes; microgliosis and astrocytosis reduction | Sun et al., 2002 |
| Intrathecal injection of r-AAV HGF in SOD1-G93A mice | 2019 | Mouse | Motor neuron protection and delay in degeneration; ERK activation implication | Lee et al., 2019 | |
| PD | In vivo naked HGF plasmid DNA transfer into the striatum in 6-OHDA models | 2006 | Rat | Protection of dopaminergic neurons from neuron death; inhibition of abnormal amphetamine-induced rotation | Koike et al., 2006 |
| In vivo naked HGF plasmid DNA transfer in the putamen using a stereotaxic technique in the MPTP model | 2009 | Monkey | Prevention of abnormal amphetamine-induced rotation in hemi-PD primates; gradual reduction of limb tremor and rigidity; prevention (reparation) of dopaminergic neuron MPTP-induced death | Koike et al., 2009 | |
| Overexpression of hHGF plasmid DNA using ultrasound-mediated gene transfer into the brain in an Aβ-infused cognitive dysfunction mouse model. | 2008 | Mouse | Amelioration Aβ-induced memory impairment; high recovery of vessel density in the hippocampus; upregulation of BDNF; significant decrease in oxidative stress; synaptic enhancement. | Takeuchi et al., 2008 | |
| SCI | Exogenous HGF administration using a replication-incompetent HSV-1 vector | 2007 | Mouse | Promotion of neuron and oligodendrocyte survival by the reduction of cleaved caspase-3 activation; angiogenesis promotion; demyelination reduction | Kitamura et al., 2007 |
| Peripheral nerve injury | Intramuscular injection of the HGF plasmid pCK-HGF-X7 around the sciatic nerve | 2018 | Mouse | Increase in myelin thickness and axon diameter | Ko et al., 2018 |
| Intramuscular injection of the plasmid pC4W-hHGF bearing human HGF | 2018 | Mouse | Nerve structure restoration; functional recovery; inflammation decrease | Boldyreva et al., 2018 | |
| Neurophatic pain | HGF gene transfer transfected by the non-viral HVJ liposome administered by repeated intramuscular injection in the CCI model | 2008 | Rat | Pain relief; reduction of P2 × 3, P2 × 4, and P2Y1 receptor mRNA levels, and of IL-6 and ATF3 mRNAs induced by CCI | Shimamura et al., 2006 |
| HGF plasmid DNA (VM202 or pCK-HGF-X7) administered by intramuscular injection in chronic constriction injury (CCI) model | 2018 | Mouse | Neuropathic pain suppression for several weeks; downregulation of the expression of pain-related markers; reduction in the number of activated microglia and astrocytes | Nho et al., 2018 | |
| Cerebral ischemia | HGF gene transfer by the non-viral HVJ liposome | 2001 | Mongolian gerbils | Prevention of neuronal cell death | Hayashi et al., 2001 |
| HGF gene transfer by the HVJ-envelope | 2006 | Rat | Increase of synaptogenesis; neurite extension promotion; prevention of gliosis | Shimamura et al., 2006 |
ALS, amyotrophic lateral sclerosis; ATF3, activating transcription factor 3; BDNF, brain-derived neurotrophic factor; CCI, chronic constriction injury; EAAT2, excitatory amino acids transporter 2; HGF, hepatocyte growth factor; HJV, hemagglutinating virus of Japan; HSV-1, herpes simplex virus-1; IL-6, interleukin 6; iNOS, inducible nitric oxide synthase; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD, Parkinson’s disease; P2 × 3, P2X purinoreceptor 3; P2 × 4, P2X purinoreceptor 4; P2Y1, P2Y purinoreceptor 1; r-AAV HGF, recombinant adeno-associated virus encoding human hepatocyte growth factor; SCI, spinal cord injury; 6-OHDA, 6-hydroxydopamine.