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Compassionate use may play an important role in responding to major public health emergencies. The Jinyintan Hospital in Wuhan launched the III phase of clinical trials of antiviral drug-remdesivir on February 6, 2020. As an unapproved drug, remdesivir raised great concerns about compassionate use in China. Compassionate use is therapeutic use of unauthorized drugs outside of clinical trials. It is used for critically ill patients with life-threatening diseases and no effective treatment means in China. Patients voluntarily apply to their medical institutions. The Center for Drug Evaluation, National Medical Products Administration shall conduct scientific and reasonable review, approval, and supervision on patients' application for compassionate medication. By analyzing and comparing the current situation of compassionate use at home and abroad, it is expected to provide thinking for the development of compassionate use system in China.

To investigate the potential of gene therapy for the treatment of chronic diseases such as hypertension, chronic heart failure, and chronic renal failure, we established the neonatal rat fibroblast line engineered to secrete the mutant human atrial natriuretic peptide (mhANP), and then transplanted the cell line into young spontaneously hypertensive rats (SHR) subcutaneously. We found that a single transplantation of the cell line caused an obvious rise in the concentration of mhANP in serum 7 d after transplantation ((135 +/- 8) vs (106 +/- 7) pg/mL, P < 0.01). The animals' blood pressure in test group was always remarkably lower than that of empty vector group within 42 d after transplantation, even though the blood pressure in all groups was constantly increasing in the process of ontogeny ((175 +/- 10) mm Hg vs (189 +/- 12) mm Hg, P < 0.05). A maximal blood pressure reduction of 33 mm Hg ((157 +/- 9) mm Hg vs (124 +/- 112) mm Hg, P < 0.01) was observed 14 d post cell transplantation. There was a marked increase in urine volume in test group from second week after treatment beginning ((5.9 +/- 0.7) mL/6 h vs (4.3 +/- 0.8) mL/6 h, P < 0.01) and the effect lasted 14 d ((6.1 +/- 1.1) mL/6 h vs (4.0 +/- 0.8) mL/6 h, P < 0.01), however the statistical difference in concentration of K+ and Na+ in serum and urine was not observed. The results suggested that subcutaneous implantation of fibroblasts-expressing mhANP significantly reduced blood pressure in young SHR during the period of ontogeny and efficiently improved their renal function and the somatic gene transfer of mhANP may have potential value in the treatment of human chronic diseases such as hypertension, chronic heart failure, and chronic renal failure.

Objective: To prolong the half-life and enhance the biological activity of the human atrial natriuretic peptide (hANP), a peptide hormone, which is synthesized and released mainly by cardiac atrial myocytes and possesses potent natriuretic, diretic, and vasorelaxant properties., Methods: The site-directed mutation technique based on polymerase chain reaction was performed to get the mutant of the human ANP gene (mhANP), and the retroviral expression vector, pLHY24, in which mhANP gene is under the transcriptional control of the human cytomegalovirus promoter, was constructed. The naked plasmid DNA of pLHY24 and positive control vector, pLHY19, in which the wild-type hNAP gene is in the same conditions as mhANP gene in pLHY24, and negative control vector, pLNCX without purpose gene, at a dose of 5 mg/kg body weight was injected intramuscularly into the rats with experimental renal disorder induced with adriamycin (ADR), respectively., Results: DNA sequencing result proved that the respected mhANP gene with the point mutations of TTC(131)/Phe-->TCC/Ser and ATG(135)/Met-->ATA/Ile has been obtained. In comparison with negative control group (87 +/- 7.1 pg/ml), a single intramuscular injection of expression vector harboring mhANP or hANP gene resulted in an obvious increase in plasma level of mhANP (107 +/- 7.8 pg/ml, t = 4.65, P < 0.01) or hANP (113 +/- 8.6 pg/ml, t = 5.71, P < 0.01) 5 days after injection. A significant elevation in the ratio of urine volume to body weight was occurred after both of mhANP gene and hANP gene delivery as compared with negative control and the effect lasted for more than 15 days. The diuretic activity of mhANP gene delivery was 1.6-, 2.0-, and 1.9-fold higher than that of hANP gene 5, 10, and 15 days after gene transfer, respectively. However, there were no statistical differences in the concentrations of K(+) and Na(+) in urine., Conclusions: Both of mhANP and hANP gene delivery into the rats with experimental nephropathy could improve their directic function obviously and the diuretic activity of the former is stronger than that of the latter significantly.

Objective: To study the inhibitive effect of subcutaneous implantation of capsule filled with fibroblasts engineered to secrete the mutant human atrial natriuretic peptide (mhANP) on blood pressure in young spontaneously hypertensive rats (SHR) and to explore the feasibility of gene therapy for the treatment of hypertension., Methods: A recombinant retroviral vector pLHY24 bearing mhANP cDNA was constructed. Primary fibroblasts derived from the skin of new born SHR were cultured and transfected with the vector pLHY24 to establish a genetically modified fibroblast line or transfected with the blank vector pLNCX. Then the two kinds of cell culture were put into specially made capsules with microholes. The capsules filled with the genetically modified allogenic fibroblasts and those with blank vector were implanted into the dorsal subcutaneous tissues of two groups of 10 young SHR respectively. The plasma ANP, blood pressure, urine volume, potassium and sodium concentrations in urine, and body weight were determined every week for 7 weeks., Results: After delivery of retroviral vector bearing mhANP gene into the packaging cell PA317 and the primary fibroblasts, immunoreactive mhANP were detected in the cell culture medium at the concentration of (5.84 +/- 0.07) and (13.37 +/- 2.36) ng.10(-6) cells.24 h(-1) respectively. One week after implantation of the genetically modified allogenic fibroblasts the plasma level of mhANP was 131 pg/ml +/- 8 pg/ml, significantly higher than that in control group (104 pg/ml +/- 7 pg/ml, t = 8.62, P < 0.001). Although the blood pressure increased along with aging after the gene transfer, an obvious delay of blood pressure increase was seen significantly lower in test group [from (129 +/- 9) to (169 +/- 9) mm Hg] than that in the control group [from (145 +/- 10) to (181 +/- 9) mm Hg, P < 0.05 or 0.01]. A maximal blood pressure reduction of 28 mm Hg in young SHR was observed 7 days after transplantation as compared with controls. In addition, there was an obvious increase in urine volume of test group 2 weeks after transplantation and the effect lasted for more than 2 weeks. However, there were no statistical differences in body weight and the concentrations of K(+) and Na(+) in urine., Conclusion: Subcutaneous implantation of the encapsulated genetically modified fibroblasts engineered to secrete mutant ANP causes a lowering effect of blood pressure in young SHR.