Analytical Report of Almazov Centre

    

Analytical Report based on the results of research state assignment in 2021

Almazov Centre participates in 14 scientific platforms of the Russian Ministry of Health and its specialists are included in the expert groups in six of these platforms. The research teams of the Centre were actively involved in shaping the research topics for these platforms.

In 2021, the Centre carried out research work under 48 state assignments, 23 grants, 17 cooperation agreements with Russian partners, 1 international MoU and 62 clinical testing protocols.

The number of scientific staff in 2021 was 695 people, and this number is constantly growing. The number of scientific staff positions went up from 1078.25 in 2020 to 1156.25 in 2021. There are 164 research departments where 242 scientists are involved in research, almost half of them being under 39 years old (152 researchers (62.8%)).

The scientific structure of Almazov Centre embraces 7 research institutes and comprises 127 research departments (100 main research departments and 27 WCRC departments) and laboratories, with leading scientists working under direction of Professor Evgeny Shlyakhto:

— two corresponding members of RAS (Prof. Konradi, Prof. Galagudza)
— 116 doctors of sciences and 323 candidates of sciences.

The total Hirsch index of the research staff is 2,519 in RSCI and 1,291 in Scopus.

Publication activities are increasing every year. In 2021, our scientists published 705 articles in top-tier journals, 166 of them were in Q1-2 journals.

Following the state assignment, 627 articles were published in 2021 with a total impact factor of 1316.7, 99.3% of publications accounting for journals with an impact factor of more than 0.3 (623 articles).

The overall impact factor of the publications made in 2021 was 1,522.3.

Intellectual propert

In 2021, the Centre obtained 37 intellectual property results, including 24 patents, 11 database certificates and 2 software certificates. Twenty-nine invention applications were filed.

The Centre got the first-ever international patent for registration of the training program “Research Management” (ID: WDTS-PC-00002664 dated 12/14/21).

A module of the advanced training program «Fundamentals of Research Management» was developed (intellectual property sections).

The created model forms the basis for the establishment of the Technology Transfer Centre in cooperation with business partners.

Clinical testing

As part of the clinical testing of new methods for prevention, diagnosis, treatment and rehabilitation, medical care is provided in 2021 under 62 protocols.

A total of 457 patients were treated over 12 months (cardiovascular surgery – 153, cardiology – 32, oncology – 28, endocrinology – 35, obstetrics and gynecology – 163, neurology and neurosurgery – 29, surgery – 8, urology – 9).

Eleven clinical testing protocols were submitted for consideration to the Ministry of Health and 4 protocols were approved to participate in the clinical testing program in 2022—2024.

The following protocols were included in the clinical guidelines following the positive decision on clinical and economic efficiency made by the Expert Council of the Russian Ministry of Health:

• 5-15 “Clinical testing of myocardium ischemic postconditioning method in patients with acute coronary syndrome with ST segment elevation”
• 5-16 “Clinical testing of diagnostic method of functional significance of coronary artery stenosis using perfusion PET to determine indications for endovascular revascularization”
• 2016-19-16 “Clinical testing of modulating cardiac contractility for CHF treatment”

Research under grant projects

In 2021, Almazov Centre carried out research under 23 grants:

— 10 grants from the Russian Foundation for Basic Research (RFBR)

— 8 grants from the Russian Science Foundation (RSF)

— 5 grants from the Ministry of Science and Higher Education, including:

• Grant to carry out major research projects on the topic “Development of new neuromodulation-based technologies for heart failure prevention and treatment”
• Grant for the state support to establish and develop world-class research centres (WCRC) carrying out R&D on the priority areas of science and technology under the federal project «Development of research, development and production cooperation» of the national project «Science and Universities»

The research team has been continuing the project “Development of new neuromodulation-based technologies for heart failure prevention and treatment”, which received a grant for 2020—2022 from the Russian Ministry of Science and Higher Education to conduct major projects in priority R&D areas as part of the subprogram “Basic research for long-term development and competitiveness of society and the state” under the State Programme of the Russian Federation for the Development of Science and Technology (completion period: 2020—2022, total project funding: RUB 300 million).

In 2021, the Centre won the competition of the Russian Ministry of Science and Higher Education to conduct research together with research and/or educational institutions from the countries of South and Southeast Asia and the Middle East as part of the cooperation under the project “Smart Technologies to Improve the Quality of Medical Care for Chronic Diseases in Large-Scale Distributed Telemedicine Systems.”

A total of 78 publications based on the results of research under grant projects were published with a total impact factor of 239.3.

The most significant grant project in 2021 was the project to establish and develop a World-Class Research Centre for Personalized Medicine (completion period: 2020—2024).

The total funding for research increased from RUB 628,411.2 thousand in 2020 to RUB 903,982.5 thousand in 2021.

Development of new neuromodulation-based technologies for heart failure prevention and treatment

The project “Development of new neuromodulation-based technologies for heart failure prevention and treatment” was carried out by the Centre’s team under agreement No. 075-15-2020 -800 dated 09/24/2020 with the Ministry of Science and Higher Education of the Russian Federation.

     

The main goal of the project was to study the fundamental mechanisms of the autonomic nervous system involved in the pathogenesis of circulatory diseases and to develop new technologies for the prevention and treatment of heart failure based on neuromodulation. In 2021, the project team obtained priority research data presented in 13 publications in leading international journals (Journal of Clinical Investigation, Journal of Cardiovascular Translational Research, Scientific Reports, International Journal of Molecular Sciences, BMC Pulmonary Medicine, etc.) and four successfully defended PhD theses.

A 3D mathematical model of ischemia-reperfusion injury in the rat and human heart was developed, making it possible to predict and heed the effect of adipose tissue hormones and vagal stimulation on the process of myocardial damage and the formation of rhythm disturbances.

Experimental studies on rodents have shown that a prolonged increase in leptin concentration associates with an aggravated severity of ischemic damage to the myocardium, an increased incidence of rhythm disturbances, an increased degree of myocardial hypertrophy and systemic inflammation. Vagal nerve stimulation attenuates myocardial ischemia damage and has an antiarrhythmic effect.

New molecular mechanisms associated with the favorable effects of sympathetic denervation on the course of pulmonary hypertension were identified.

A new large animal model of atrial fibrillation was developed and validated using high-frequency burst pacing of certain cardiac structures.

The preliminary experiments studying the effects of local administration of liposome-encapsulated selective neuromodulators on the severity of atrial fibrillation have shown that these substances can reduce the severity of atrial fibrillation.

World-Class Research Centre for Personalized Medicine

In 2021, the WCRC for Personalized Medicine headed by Academician of the Russian Academy of Sciences Evgeny Shlyakhto continued research in concert with the Institute of Experimental Medicine in the priority area of “Personalized medicine, high-tech healthcare and health-preserving technologies.”

The goal of the project is to reduce morbidity and mortality from diseases through the innovative development of healthcare based on the development and implementation of modern technologies of personalized medicine.

Major research areas of WCRC:

• Population genetics and polygenic non-communicable diseases
• Unknown, rare and genetically determined diseases
• Oncology
• Infectious diseases, microbial and antimicrobial therapy

WCRC comprises four research units:

• Research Department of Genetic Risks and Personalized Prevention
• Research Centre of Unknown, Rare and Genetically Determined Diseases
• Research Centre of Personalized Oncology
• Research and Educational Centre for Molecular Basis of Interaction Between Microorganisms and Humans

Scientific journals

Almazov Centre is the founder of seven scientific journals and the internal newsletter of Almazov Centre, one of which won the Russian Scientific Journal Award of the Russian Ministry of Education and Science.

Currently, Arterial Hypertension has an impact factor of 1.2, is listed in the RSCI, Scopus and WOS, the journal is recommended by the Higher Attestation Commission. The journal won the Russian Scientific Journal Award of the Russian Ministry of Education and Science.

Translational Medicine has an impact factor of 0.5, the journal is recommended by the Higher Attestation Commission and is included in the RSCI.

Russian Neurosurgical Journal Named After Professor Polenov has an impact factor of 0.38, is recommended by the Higher Attestation Commission and is included in the RSCI.

In 2021, the new journal was initiated – Russian Journal of Personalized Medicine.

In 2020, the Almazov Centre team published 12 monographs as well as textbooks and teaching guides.

International collaboration

The World-Class Research Centre for Personalized Medicine is engaged in a number of international collaborative projects involving worldwide acclaimed scientists with outstanding discoveries.

In 2021, the Centre engaged the following world renowned scientists:

• Alberico L. Catapano (Italy), Professor of Pharmacology at the University of Milan, Past President of the European Atherosclerosis Society (EAS), Director of the Centre for the Study of Atherosclerosis at the Bassini Hospital, Chairman of the EAS/European Society of Cardiology (ESC) guidelines for the treatment of dyslipoproteinaemias and Director of the Italian Society for the Study of Atherosclerosis.
• Andrea Baragetti (Italy), Post-Doctoral Researcher, Department of Pharmacological and Biomolecular Sciences, University of Milan.
• Paolo Magni (Italy), Full professor of Biomedical Engineering at the Università degli Studi di Pavia; Associate Professor, Department of Pharmacological and Biomolecular Sciences, University of Milan.
• Jeroen Bax (Netherlands), Director of Non-invasive Imaging at the Leiden University Medical Center.
• Roberto Ferrari (Italy), Emeritus Professor, University of Ferrara.
• Luisa Marracinо (Italy), Researcher, University of Ferrara.
• Anna Orlova (Sweden): Professor at the Department of Medicinal Chemistry, Associate Professor at the Department of Immunology, Genetics and Pathology, Uppsala University.
• Vladimir Tolmachev (Sweden): Professor at the Department of Immunology, Genetics and Pathology, Head of Research, Department of Radiation Medicine, Uppsala University.
• Fausto Pinto (Portugal): Dean of the Faculty of Medicine, University of Lisbon, President, Executive Board of the Lisbon Academic Medical Centre (CAML, 2019—2021), President of the World Heart Federation (WHF, 2021—2022).

The collaboration includes joint biobanking of blood samples of patients with acute coronary syndrome for subsequent analysis using omics technologies (genomics, proteomics, metabolomics, pharmacogenomics) as the key tools allowing the use of a personalized approach in medicine and real clinical practice.

Prof. Catapano participates in the interpretation of the results obtained from genetic testing of patients with severe clinical phenotype of familial hypercholesterolemia. He provides expert support and comments in the development of the educational program “Modern aspects of pathophysiology of vascular inflammation and new approaches to its treatment” and its parts “Modern diagnosis and personalized therapy for genetic lipid metabolism disorders” and “New biomarkers for risk assessment of atherosclerotic progression.”

Andrea Baragetti participates in the joint development of educational modules of the program “Modern aspects of pathophysiology of vascular inflammation and new approaches to its treatment”, section “Modern diagnosis and personalized therapy of genetic lipid metabolism disorders.”

Prof. Magni participates in the development of the educational modules of the program “Modern aspects of pathophysiology of vascular inflammation and new approaches to its treatment”: “New biomarkers for risk assessment of atherosclerotic progression” for the training of cardiologists focused on personalized medicine. He also contributes to the writing of an article in the Q1-Q2 journal describing genetic and epigenetic approaches in cardiovascular risk prediction using multi-omics technologies and the design of the patient registry.

Prof. Bax gives lectures on imaging and personalized medicine in cardiology and is a key speaker representing the WCRC for Personalized Medicine at the WCRC Integration Summit – World-Class Research Centres for Health Care as a Tool for Advanced Development of the Industry on November 30, 2021.

As part of collaboration with the WCRC for Personalized Medicine, Prof. Ferrari gives lectures on calcification and cardiovascular risk factors; participates in online meetings dedicated to the joint plans and implementation of the program for the establishment and development of WCRC and gives advisory sessions on calcification and cardiovascular risk factors with the specialists of research laboratories of research area “Unknown, rare and genetically determined diseases.”

As part of her onsite training, Luisa Marrachino is carrying out the research work “Analysis of the role of Dll4 and Jag1 genes in pathological osteogenic differentiation in aortic valve calcification.” Research will result in the preparation of a manuscript for publication in a scientific journal indexed in Web of Science.

A major area of the WCRC for Personalized Medicine is the development and study of the properties of PSMA ligand radiopharmaceuticals for theranostics of prostate cancer in collaboration with colleagues from Uppsala University in Sweden studying the properties of diagnostic efficacy for dual bombesin/PSMA-targeting radioligand.

Over the past years, Prof. Orlova has been developing radiopharmaceuticals for nuclear medicine, focusing on the creation, study of the properties and diagnostic efficacy of bombesin antagonist-based radioligands, as well as radiopharmaceuticals based on several receptor ligands, which are used for theranostics of prostate cancer. At the Centre for Personalized Medicine, Professor Orlova supervised a trial synthesis of a dual bombesin/PSMA-targeting radioligand.

Prof. Tolmachev is engaged in the creation, study of the properties and diagnostic effectiveness of radiopharmaceuticals in the diagnosis of tumors of various sites based on antibodies, incl. mini-antibodies, affibody, scaffolds, radioligands. He possesses unique knowledge and skills in radiochemical synthesis and prerequisites for obtaining radiopharmaceuticals with desired properties.

Prof. Pinto is a scientific advisor and contributor to the course of lectures on “Personalized cardiology and imaging.”

Collaboration with the world renowned scientists is a way to exchange experiences, achieve new goals and improve the diagnosis and treatment of many complex and understudied diseases.

Core facilities

Currently, Almazov Centre has 2 core facilities in place:

–  Biobank Core Facility
–  Preclinical Translational Research Centre

New Biobank

In order to implement the innovative program of the World-Class Research Centre for Personalized Medicine, Almazov Centre established a new division of the Biobank at the Scientific and Educational Medical and Biological Centre for Gifted Youth “Solnechny”.

This new facility will carry out high-tech processing, labeling and safe storage of biological collections obtained in the course of research as part of WCRC activities.

In particular, the collections of unique samples will form the basis for the effective functioning of the Competence Centre for Hereditary, Rare and Understudied Diseases established in 2021 as part of the World-Class Research Centre. The created collections of biological samples will serve to implement the main research goals: identification of new specific genetic determinants of congenital diseases and the molecular mechanisms of their development; creation of experimental cell and animal models for testing new genetically engineered and gene therapy drugs for the treatment of hereditary diseases; the use of breakthrough genetic technologies, including eQTL mapping; assessment of expression and epigenetic profiling in order to reveal new phenotypic mechanisms of genetic breakdowns and the development of drugs targeting these mechanisms; creation of a scientific and clinical biomedical ecosystem that develops and implements diagnostic and treatment technologies based on personalized medicine, including disease biomodelling; genome modification and creation of gene therapy drugs and biomedical cell products using genome editing technologies to improve the quality of treatment and reduce mortality in various genetically determined cardiovascular, autoimmune as well as rare and understudied diseases.

Biobanking is a vital component of research, and the availability of a biobank as a unit opens up tremendous opportunities for basic, exploratory and applied research both in various fields of biomedicine and at the intersection of fields, which is recognized worldwide.

Preclinical Translational Research Centre

    

The Preclinical Translational Research Centre is a new facility of Almazov Centre conducting a wide range of state-of-the-art scientific and preclinical studies in accordance with all international standards.

The Preclinical Translational Research Centre with its specialized nursery of laboratory animals provides an opportunity to conduct unique experimental studies in compliance with all international standards.

The Centre is equipped and staffed to handle basic research of various complexity, including the study of the mechanisms underlying the onset and progression of socially significant diseases, the development of new methods for their prevention, diagnosis and treatment as well as the development and validation of various disease experimental models, from in silico to in vivo.

The Centre has a nursery for laboratory rodents with vivariums and areas for larger animals (minipigs, swine) and aquatic animals (Danio rerio and Xenopus laevis species). The Department of Biological Test Systems and Models is equipped to generate genetically modified rodents (transgenic and knockout mice) and fish.

The Centre provides a range of services for preclinical studies of drugs, medical devices, medical technologies and biomedical cell products, including in determining the scope of preclinical studies, conducting experimental studies to assess safety and efficacy, developing a study design, and reporting on the conducted preclinical studies in accordance with the modern regulatory requirements of the Russian Federation and GLP regulations.

Translational Medicine Cluster

The effective work of the research team allowed the Centre to become a leading medical research institution in Russia and build a research and educational cluster involving scientific institutions, universities and manufacturing companies.

    

Goal of the Cluster:

To create a medicine segment based on breakthrough technologies, new markets of high-tech products and services and fast integration of advanced findings in medical and pharmaceutical industries.

Focus areas of the Cluster cover the following economic sectors:

• Medicine and healthcare
• Biotechnologies
• Pharmaceutical industry
• Chemical industry
• Automation and electronics
• New materials production

Cluster projects in 2021:

1. Development of the Life Sciences section for the Science and Technology Concept of St. Petersburg.
2. Organization and holding of the plenary session of the St. Petersburg International Innovation Forum with the participation of St. Petersburg Governor Alexander Beglov, Head of RUSNANO Anatoly Chubais and other top-level executives.
3. The first stage of the Ecosystem S3 project as part of the Interreg BSR EU program “Development of methodology and audit / mapping of the existing interaction practice in the provision of medical care in St. Petersburg healthcare facilities”
4. Cooperation with the Committee for Industrial Policy, Innovation and Trade of St. Petersburg, the Centre for Cluster Development of St. Petersburg.