ACT4HEALTH

The increasing incidence of both communicable diseases – e.g. emerging viral infections, antimicrobial resistance and zoonoses – and non-communicable diseases – e.g. cancer and autoimmune diseases – has made the need for more effective, rapid, sensitive and accessible diagnostic tools increasingly evident. This need has also contributed to a paradigm shift towards the so-called “4P medicine” (predictive, preventive, personalised and participatory), which aims to move beyond the traditional reactive healthcare model, focused on the management of established diseases, towards a proactive system centred on early diagnosis, the reduction of risk factors, personalised patient care, and the active involvement of patients in decision-making processes. However, the large-scale implementation of 4P medicine still faces numerous methodological, organisational and technological challenges.

Among the main challenges is the need to:

• have validated and reliable biomarkers and diagnostic devices, in order to ensure the reproducibility of results and their applicability in clinical practice and public health programmes;

• standardise protocols for the collection, storage and analysis of biological samples, in order to ensure the consistency and comparability of data generated in different settings.

Another crucial aspect concerns the development and adoption of advanced digital infrastructures, including interoperable and secure bioinformatics platforms capable of efficiently managing large volumes of heterogeneous data and integrating with existing healthcare databases. Finally, it is essential to design intuitive and inclusive digital tools (in line with the principle of participation) that facilitate the multidirectional exchange of information among citizens, healthcare professionals and public decision-makers, promoting transparency, patient empowerment, and greater informed adherence to prevention and treatment strategies.

The ACT4HEALTH project aims to contribute to the large-scale implementation of 4P medicine through:

• a multidisciplinary and integrated approach combining molecular biology, omics technologies, preclinical models and advanced diagnostic platforms, with the aim of defining and validating innovative diagnostic approaches and technologies for communicable diseases (with a particular focus on infectious diseases, which are the focus of the activities carried out within the INF-ACT Research Programme) and non-communicable diseases (e.g. oncological and autoimmune diseases);

• the promotion of processes for the capitalisation and valorisation of results across the R&I value chain in the field of diagnostics.

Building on the experience gained and the results generated within the INF-ACT Research Programme, the INF-ACT Foundation, with the contribution of 14 research institutions distributed across 20 Operational Units, has established a structured and multidisciplinary programme of industrial research and experimental development. This programme will capitalise on the main diagnostic-related results achieved within the INF-ACT Extended Partnership. INF-ACT research activities have focused on fundamental research in the field of emerging infectious diseases. Through ACT4HEALTH, we will leverage the technological versatility of the approaches developed to extend and apply the diagnostic methodologies to other diseases as well (e.g. oncological and autoimmune diseases).

More specifically, ACT4HEALTH aims to make a significant contribution to technological development and to strengthening strategic research and innovation value chains in diagnostics through:

• the development of an advanced, scalable and interoperable bioinformatics platform for the integrated analysis of multi-omics data (genomic, transcriptomic, epigenetic, proteomic and metabolomic);

• the implementation of an experimental multi-parametric analysis approach based on advanced technologies enabling the molecular profiles of cells, tissues and fluid matrices obtained from patients to be studied at unprecedented resolution;

• the development of innovative technologies for the diagnosis and investigation of drug resistance in zoonoses;

• the development of methodologies for the functional monitoring of immune tolerance and imaging as diagnostic and predictive tools for disease progression and response to pharmacological therapies;

• the development of biosensors capable of detecting alterations in different signals with pathogenic relevance in major chronic airway diseases (asthma and chronic obstructive pulmonary disease, COPD).

In addition, the INF-ACT Foundation will implement actions aimed at strengthening strategic R&I value chains in the health sector through the publication of competitive calls for contract research to support the valorisation of the most relevant results at national level. These actions will promote the integration of specific technological expertise and the implementation of high-TRL Proof-of-Concept projects aligned with the objectives of ACT4HEALTH.

The ACT4HEALTH project is structured into four Work Packages (WPs):

• WP1 – ACT4HEALTH-OMICS (WP leader: Prof. Gianluigi Franci – UNISA) addresses the challenge of multi-omics data integration, contributing to the development of standardised, interoperable and clinically applicable tools. Its objective is to promote the adoption of 4P medicine models. WP1 activities include: (i) the development and validation of technologies for early diagnosis, risk stratification and personalised treatment of oncological, infectious, autoimmune and cardiovascular diseases; and (ii) the creation of bioinformatics platforms and workflows for the integrated analysis of multi-omics data.

• WP2 – ACT4HEALTH-BIOMARKER (WP leader: Dr Maria Lina Tornesello – INT PASCALE) is structured around Proof-of-Concept projects aimed at investigating molecular biomarkers for the early diagnosis of communicable and non-communicable diseases and at developing advanced diagnostic technologies with potential clinical and therapeutic applications. WP2 research activities include: (i) the multi-parametric analysis of communicable and non-communicable diseases aimed at improving prevention and early diagnosis protocols and personalising therapeutic pathways; (ii) the integrated application of omics techniques for the development of integrated technologies and molecular studies to improve diagnosis and the management of drug resistance in zoonoses; and (iii) the development of a multiplex system of nanostructured, portable and miniaturised electrochemical sensors for the real-time detection of biomarkers of respiratory damage, with potential extension to other clinical fields.

• WP3 – ACT4HEALTH-IMMUNO (WP leader: Prof. Giuseppe Matarese – UNINA) is aimed at developing an integrated and innovative approach for monitoring immune tolerance in autoimmune diseases, with the goal of providing diagnostic and predictive tools for the early diagnosis of autoimmune diseases (e.g. multiple sclerosis) and for assessing disease progression and response to pharmacological therapies. In particular, WP3 activities have been defined with the objective of developing and validating an integrated approach to monitoring immune tolerance in autoimmune diseases, including: (i) an immunological assay to measure immune tolerance in subjects with autoimmune diseases; and (ii) the development of fluorescent PROTACs as diagnostic and therapeutic biosensors.

• WP4 – ACT4HEALTH-COCO (WP leader: Prof. Federico Forneris – INF-ACT) comprises activities supporting the industrial research and experimental development that the INF-ACT Foundation will carry out for the benefit of the ACT4 Partnership, in order to ensure the achievement of the project’s objectives and targets, valorise the products generated, and promote the integration of expertise. In particular, WP4 aims to complement the activities proposed under WPs 1–3 of ACT4HEALTH through a series of competitive “cascade” calls for collaborative research contracts supporting innovation in advanced diagnostics, investing in three main value-chain areas: results valorisation, access to advanced technologies, and Proof-of-Concept projects.

Through the implementation of the proposed activities and the consolidation of the collaborations established within the INF-ACT Research Programme, ACT4HEALTH will make a significant contribution to technological development in the field of diagnostics, the dissemination and adoption of 4P medicine, and the strengthening of strategic R&I value chains.

Realized with the contribution of the European Union under the National Research, Innovation and Competitiveness Programme for the Green and Digital Transition 2021–2027 (PN RIC 21–27), Call for Proposals DD 307 of 18 March 2025, Action 1.1.2 – Support for a limited number of strategic research value chains in the Less Developed Regions.