Gene therapy of damaged nerves
Gene from liver cells helped nerve regeneration
MSU Press Service
Russian scientists, in collaboration with doctors from Lomonosov Moscow State University, proposed using liver cell growth factor to restore peripheral nerves, which are often damaged due to limb injuries or during operations. In the experiment, the gene improved the functioning of the limbs in mice, and soon it will be possible to start clinical trials if the drug proves its safety. The work of Boldyreva et al. Plasmid-based gene therapy with hepatocyte growth factor stimulates peripheral nerve regeneration after traumatic injury is published in the journal Biomedicine and Pharmacotherapy.
Approximately every fifth fracture is accompanied by injury to peripheral nerves – that is, not related to the central nervous system (brain and spinal cord). Sometimes these injuries appear due to other wounds of the limbs or during surgical operations. Damage to peripheral nerves not only causes painful sensations, but can also deprive the patient of control over the limb and can make him disabled.
The damaged peripheral nerve can regenerate, or recover. But often patients do not receive treatment on time, or this recovery is too slow.
Scientists from Russia and Taiwan have proposed to solve this problem using a gene that causes liver cells to grow (hepatocyte growth factor, or HGF). The human hepatocyte growth factor was not chosen by chance: its ability to protect nerve cells from damage and make blood vessels grow without causing inflammation has long been known (clinical trials are also being conducted in these areas).
"We have for the first time established the effectiveness of gene therapy using human hepatocyte growth factor (HGF) for the treatment of mechanical nerve injury," co–author Pavel Makarevich, PhD, head of the Laboratory of Gene Cell Therapy at the Institute of Regenerative Medicine of Moscow State University and Associate Professor of the Department of Biochemistry and Molecular Medicine at the Faculty of Fundamental Medicine of Moscow State University, told about the successful study. – The developed approach relates to the field of gene therapy – a constantly developing field of biomedicine, which is becoming increasingly widespread in the clinic in the world."
For the experiments, the scientists used a mouse model of peripheral nerve crushing, which reproduces the adverse effects of injuries or certain operations. To deliver the gene of liver cells to the nerves and make it work, scientists have embedded it in plasmids – ring DNA. In animal cells where plasmids were injected, a protein began to synthesize and accumulate from the HGF gene, which performed its usual biological functions: stimulated regeneration and growth of cells and blood vessels, suppressed cell death and reduced inflammation. Due to this, after the introduction of the plasmid with the HGF gene, the damaged nerve was regenerated in mice, its electrophysiological parameters and the functioning of the injured limb improved.
"The work was one of the results of long–term cooperation of the Faculty of Fundamental Medicine of Moscow State University with scientists and doctors of the Institute of Experimental Cardiology of the NMIC of Cardiology of the Ministry of Health," Pavel Makarevich explained. – The work was carried out with the support of a grant from the Russian Academy of Sciences, within which, together with a foreign collaborator (National Taiwan University), gene and cellular approaches to peripheral nerve regeneration are being developed." Also, the co-authors of the article were scientists from MIPT and the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences.
The authors believe that the results will soon allow us to move on to the first clinical trials on people with various peripheral nerve injuries. This will happen after a preclinical safety assessment of the drug.
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