Personalized drug therapy using the tools of metabolomics and pharmaceutical technology
Personalized drug therapy using the tools of metabolomics and pharmaceutical technology

Metabolomic research (studying body responses to pathophysiological effects by assessing the levels of low molecular weight metabolites in biofluids and tissues and their dynamics) forms the basis of the project. This research is a modern scientific approach to understanding how a disease has emerged, to diagnosis of diseases and optimization of medicinal treatment. Two main directions are under the implementation: the first involves practicing screening methods for 158 metabolites, lipid metabolism mediators, using HPLC-/MS/МS method and its application in  vitro experiments when studying CNS inflammatory conditions (assessment of release levels of prostaglandins and rezolvins - the most important pro- and anti-inflammatory lipid mediators); the second in vivo direction is based on comparing the blood metabolome of healthy and sick patients (City Clinical Hospital №24 ), developing an algorithm for the effective treatment of arterial hypertension with ‘inflammatory’ component. Furthermore, in vivo test system is being developed under the project. It is used for comparative express assessment of the anti-inflammatory activity of drug products. 

Project goals
  • Developing new modern methods of prevention.
  • Diagnosis and treatment of the most important human diseases and introducing them into clinical practice.
Project leader All participants
Viktor Chistyakov

Viktor Chistyakov

Project results
The methods of qualitative and quantitative analysis of 158 metabolites, lipid metabolism mediators, using HPLC-/MS/МS method were practiced. The research was aimed at selecting optimal extraction (LLE, SPE) conditions of the spectrum of the studied metabolites from complex matrices of cell cultures and biofluids. The validation of the adapted methods for culture-based liquids was done, the necessary and sufficient parameters (precision, accuracy, linearity, limit of quantitation, etc.) were established.
The possibility of quantitative determination of the biomarkers of the blood serum of the inflammatory process caused by the subcutaneous injection of a 0.1% solution of carrageenan into the rat’s paw was studied. Various endogenous compounds are involved in the inflammatory process. They can be divided into two groups: pro-inflammatory (inducing inflammatory response) and anti-inflammatory (final inflammation). Their ratio may change over time. The metabolism of the rat’s blood serum in 3 and 24 hours (n=3) after the inflammatory response starts was analyzed with the HPLC-/MS/МS equipment (Shimadzu 8040), Lipid Mediators v.2 and SPE (Chromabond HR-X 60 mg cartridges). The 8-iso-PGE2, PGE2, PGD2 (pro-inflammatory) and 8-iso-PGA2, PGA2, PGJ2 (anti-inflammatory) prostaglandin groups were selected from the obtained metabolite profile.
The preliminary search for the markers of arterial hypertension was made. The research was carried out in City Clinical Hospital №24 of Moscow of the Department of Health of Moscow. The research was aimed at discovering new specific biomarkers associated with pathogenesis of arterial hypertension by analyzing the biomarkers of metabolomes. The new prospective marker was identified. This is 12-hydroxyheptadecatrienoic acid (12-HHT, C17H28O3) - arachidonic acid metabolite. The ratio of the 12-HHT metabolite in the groups (n = 5) of healthy subjects / patients with AT = 25 / 1.
The biomaterial (P.A. Hertsen Moscow Oncology Research Centre, a branch of the Federal State Budgetary Institution National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation) was collected from the oncology patients with two types of cancer: breast and colorectal cancer and with different disease severity (over 70 samples were collected), the biomaterials of the control group (healthy subjects) are being collected in order to detect diagnostic markers of the socially significant diseases.
Equipment All list
Jeol JMS GCmate II (GC/МS)
Quantitative and qualitative analysis of complex multicomponent systems.
Agilent Technologies 6340 Triple Quad LC/MS (HPLC-/MS/МS)
Highly sensitive determination of medicinal substances and their metabolites in biological media of humans and animals.
Bruker micrOTOF-Q II (HPLC-/MS/МS)
Highly sensitive determination of medicinal substances and their metabolites in biological media of humans and animals.
Shimadzu LC/MS – 8040 (HPLC-/MS/МS)
Quantitative and qualitative analysis of complex multicomponent systems.
Jeol JNM-ECA 600 NMR-spectrometer
Quantitative and qualitative analysis of complex multicomponent water organic systems, conducting metabolomic studies.
Application area
  • Clinical Pharmacology
  • Early diagnosis
  • Screening of anti-inflammatory activity of drug candidates
Partners

City

Moscow, Russia

Subject of cooperation:
Clinical studies

City

Moscow, Russia

Subject of cooperation:
Collecting oncology patients’ biomaterial for research