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Vol 34(2018) N 4 p. 37-50; DOI 10.21519/0234-2758-2018-34-4-37-50
E.P. Sannikova1, N.V. Bulushova1, S.E. Cheperegin1, I.A. Zalunin1, F.A. Klebanov1, T.S. Gracheva1, V.L. Yurin1, N.V. Rykalina1, E.V. Askerova1, S.V. Yarotsky1, O.G. Tatarnikova2, N.V.Bobkova2, D.G. Kozlov1*

Specific Activity of Modified Human Recombinant Glucagon-Like Peptide 1

1State Research Institute for Genetics and Selection of Industrial Microorganisms of National Research Center "Kurchatov Institute " (NRC "Kurchatov Institute " - GOSNIIGENETIKA), 117545, Moscow Russia
2Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moskovskaya Oblast, Russia

*dg_kozlov@genetika.ru
Received - 10.05.2018; Accepted - 04.06.2018

References

An original therapeutic Glypin for the medication of human diabetes mellitus type II has been developed. A completely biosynthetic modified human recombinant glucagon-like peptide (rmGlp-1) isolated from E. coli cells is an active pharmaceutical substance of Glypin. In addition to the GLP-1 portion with the well-known Ala8Gly substitution, the rmGLP-1 protein contains a helper amino acid sequence on the C-terminus that includes the heparin-binding peptide of human HB-EGF. A commercial preparation of Lixumia served as main reference compound to which the Glypin specific activity was compared. During the preclinical studies of both medicines it was shown that Glypin and Lixumia have the following similar properties: (1) close effectiveness and time of action under the subcutaneous and intramuscular injection; (2) comparable insulinotropic activity confirming the occurrence of the common mechanism of activity of Glypin and the reference preparations; (3) resembling therapeutic effect under long-term use. Based on these data, the subcutaneous injection was chosen as the main therapeutic way for the Glypin introduction; the single dose for Glypin preclinical research was established equal to 100 ug/kg, and that for the human therapy was defined as 0.75 mg and 1.5 mg. A statistically reliable positive effect of Glypin intranasal introduction was found using mouse models with sporadic Alzheimer disease. The similar characteristics of Glypin and Lixumia shown in our studies make it possible to anticipate their equal efficacy under the same once a day therapeutic application.

agonist of GLP-1 receptors, antiglycemic preparation, glucagon-like peptide, Lixumia, diabetes mellitus.

This work was supported by the Ministry of Education and Science of RF (State Contract 14.N08.12.1038).



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