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Subject ViroMed Announces Publication of VM202’s MoA in Reducing Neuropathic Pain
Writer ViroMed
Date 2018/04/17

ViroMed Announces Publication of VM202’s MoA in Reducing Neuropathic Pain

 

Innovative biologics developer ViroMed (084990: KS) recently announced the publication of study results that demonstrate how the company’s lead gene therapy product VM 202 reduces neuropathic pain symptoms. The study showed that VM202 ameliorates neuropathic pain by suppressing pain-related factors caused by nerve damage in the central and peripheral nervous systems, and by regulating inflammatory reactions. A paper containing the results was published online on April 17 in the Federation of American Societies for Experimental Biology (FASEB) Journal.

(URL: http://www.fasebj.org/doi/10.1096/fj.201800476R)

 

It is the first study to reveal VM 202’s mechanism of reducing pain in diabetic neuropathy in terms of molecular biology and histopathology. As the first study that shows that intramuscular administration of VM 202 may alleviate the pathologic condition of the pain circulatory in the central nervous system (CNS) regarding neuropathic pain, it also implies VM202’s potential to become a DMD (disease-modifying drug) that can fundamentally change the course of disease progression in diabetic neuropathy.  

 

The research team investigated how VM 202 ameliorates neuropathic pain by examining three aspects in animal experiments: whether the therapeutic gene HGF-X7, delivered through intramuscular injection of VM202, produces HGF proteins in the intended sites in the body; the impact VM 202 has on neuropathic pain; and analysis of how pain-related factors change in the dorsal root ganglion (DRG) and the spinal cord in the CNS, which are involved in the delivery of pain signals.  

 

Regarding HGF proteins production, intramuscular injection of VM202 in a chronic constriction injury (CCI)–induced neuropathic pain mouse model generated the expression of HGF proteins in the injected muscle, sciatic nerve, and DRG.

To examine the impact of VM202 on neuropathic pain, mechanical allodynia and thermal hyperalgesia behavioral tests were conducted on CCI models. In the mechanical allodynia behavioral test in CCI mouse models, the VM202 administration group showed a decrease in excessive sensitivity to normally painless stimuli, suggesting that VM202 may attenuate nerve sensitivity to external physical stimuli in painful situations. In the thermal hyperalgesia behavioral test, while the control group sensitively perceived and over-reacted to thermal stimuli, such reaction was suppressed in the VM 202 administration group, suggesting that VM202 may attenuate nerve sensitivity to thermal stimuli as well.

Animals induced with neuropathic pain show higher expression of CSF 1, ATF 3, calcium channel subunit α2δ1, factors known to be involved in pain induction, in the DRG. Administration of VM202 suppressed the expression of these pain-related factors. Furthermore, the proliferation and activation of microglia and astrocyte, which are involved in neuro-inflammatory response known as the major cause of neuropathy, were suppressed. In summary, it was confirmed that VM 202 could control neuropathic pain by regulating inflammatory response and suppressing factors that contribute to pain in the central and peripheral nervous system.  

 

Sunyoung Kim, DPhil, CSO of ViroMed, commented “The study’s findings show that VM202 can ameliorate neuropathic pain through a mechanism different from analgesics currently prescribed for diabetic neuropathy patients. The excellent long-term pain relieving effects observed in our clinical trials are most likely due to these differentiated biological activities of VM202. We plan to continuously submit papers, investigating VM202’s mode of action on the nervous systems and its correlation with pain reduction, to scientific journals. We are certain that these findings will provide scientific evidence to position VM202 as a fundamental, effective and safe treatment for diabetic peripheral neuropathy.

 

■ About the journal

The FASEB Journal is a leading global journal publishing international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research.

* Impact factor 5.498 in 2016, five-year average 5.435

 

■ Terminology

1) Dorsal root ganglion (DRG): Nerve cell cluster located in the posterior root of a spinal nerve, where sensory nerve cells delivering painful and tactile sensation are concentrated. In normal conditions, DRG serves as a relay base in transmitting painful sensations through nerve fibers; in diseased conditions, it restores nerve cells by mobilizing neurotrophic factors.

2) Sciatic nerve: A large peripheral nerve that runs down behind the thighs, responsible for sensation in the feet and outer part of the lower legs, and movement in the back of the calves, among others

3) Microglia: A type of neuron that are responsible for immune function in the brain, plays an important role in the neuro-immune interaction within the nervous system

4) Astrocyte: A type of neuroglia in the CNS, characterized by fibrous or protoplasmic forms