Periodic Reporting for period 1 - CRYSTAL3 (Commercial & Research Opportunity for Cysteinyl Leukotriene Signalling in Ocular & CNS Dysfunction, Cancer and Cardiovascular Disease)
Berichtszeitraum: 2021-01-01 bis 2022-12-31
According to the World Economic Forum, more than 2.5 billion people suffer from vision impairment, and ocular diseases place a direct economic burden of around €20 billion on European countries. Brain disorders, such as dementia and neurodegeneration, also have a significant economic impact of about €800 billion annually, yet few effective treatments exist for these disorders.
The World Health Organisation estimates that cancer is responsible for 1 in 6 deaths, with incidence projected to grow to 29 million by 2040. In Europe, cancer healthcare costs are around €57 billion annually. Cardiovascular diseases are the main cause of death worldwide, with healthcare costs estimated at €100 billion each year, and over 15 million people suffering from heart failure in Europe alone.
To address these issues, CRYSTAL3, an international consortium funded by EU Horizon 2020 with €887,800, is investigating a specific cell signalling process observed across a range of human diseases. The consortium includes 12 partners, located in 8 countries, and is led by Professor Breandán Kennedy from UCD School of Biomolecular and Biomedical Sciences in UCD Conway Institute. The project, which began in January 2021, focuses on commercial and research opportunities related to an inflammation-related signalling pathway that is relatively unexplored.
At the center of this pathway are powerful molecules called cysteinyl leukotrienes (CysLTs) that are involved in the body's response to fight injury or pathogens. CysLT signalling receptors are found throughout the body, including the lungs, colorectum, heart, brain, and eyes. While drugs targeting CysLT receptors are currently prescribed to treat airway inflammation, recent research suggests that CysLT signalling may also be involved in regulating cells in cancer, cardiovascular disease, and diseases of the eye and central nervous system.
The CRYSTAL3 consortium aims to determine how CysLT signalling links to these diseases, explore potential targeted therapies, and co-develop products and services that can be commercialized. In addition to developing treatments for these burdensome diseases, CRYSTAL3 provides an opportunity to enhance intersectoral training, career development, and transnational mobility of researchers in Europe.
The World Health Organisation estimates that cancer is responsible for 1 in 6 deaths, with incidence projected to grow to 29 million by 2040. In Europe, cancer healthcare costs are around €57 billion annually. Cardiovascular diseases are the main cause of death worldwide, with healthcare costs estimated at €100 billion each year, and over 15 million people suffering from heart failure in Europe alone.
To address these issues, CRYSTAL3, an international consortium funded by EU Horizon 2020 with €887,800, is investigating a specific cell signalling process observed across a range of human diseases. The consortium includes 12 partners, located in 8 countries, and is led by Professor Breandán Kennedy from UCD School of Biomolecular and Biomedical Sciences in UCD Conway Institute. The project, which began in January 2021, focuses on commercial and research opportunities related to an inflammation-related signalling pathway that is relatively unexplored.
At the center of this pathway are powerful molecules called cysteinyl leukotrienes (CysLTs) that are involved in the body's response to fight injury or pathogens. CysLT signalling receptors are found throughout the body, including the lungs, colorectum, heart, brain, and eyes. While drugs targeting CysLT receptors are currently prescribed to treat airway inflammation, recent research suggests that CysLT signalling may also be involved in regulating cells in cancer, cardiovascular disease, and diseases of the eye and central nervous system.
The CRYSTAL3 consortium aims to determine how CysLT signalling links to these diseases, explore potential targeted therapies, and co-develop products and services that can be commercialized. In addition to developing treatments for these burdensome diseases, CRYSTAL3 provides an opportunity to enhance intersectoral training, career development, and transnational mobility of researchers in Europe.
We have provided in our progress report by end of Period 1, 3 executive summaries updating on the research progress achieved within each of the scientific work packages in CRYSTAL3 (WPs 1, 2 and 3) during first Period of de project (January 2021 to December 2022). Detailed secondment reports by those fellows who have completed their secondments are available for the Commission upon request. Also, the original data sets generated during secondments are safely stored and available, subject to IP protection measures and confidential disclosure agreements. Finally, we highlight the 1 patent filed, and the 9 scientific publications in peer-reviewed journals achieved to date, which involve different academic and non-academic members of the consortium.
CRYSTAL3 has made significant contributions in five main areas during the first 2 years of the project (2021 and 2022, P1).
Firstly, it has facilitated the development of participating academic and non-academic institutions by promoting cross-sectoral research and innovation in Europe, enabling them to appreciate their different priorities, strategies, and management approaches while working effectively with each other. For instance, all SMEs in the consortium have grown in terms of size and turnover during this period, and several participants have been awarded new grants to expand or continue collaborations initiated in CRYSTAL3.
Secondly, the project has promoted the career development of 20 MSCA fellows who gained cross-sectoral expertise, which has accelerated their career transitions to industry or given them the confidence to return to academia to broaden their research acumen.
Thirdly, CRYSTAL3 has achieved significant scientific results, including nine peer-reviewed publications, 11 posters presented at international conferences, and all deliverables linked to technical WPs 1-3, which are discussed in more detail in the report.
Fourthly, the project has raised society's awareness of the research's impact through various outreach activities, such as the Uveal Melanoma Awareness Campaign and the Virtual School/Lab International Visits organized in 2021.
Finally, CRYSTAL3 has developed various items with significant potential for enhancing treatments and diagnostic tools for patients. For example, the consortium is working with the assistance of EU-Horizon Results Booster Services, on further validation and business plan development for a novel Panel of Cancer Biomarkers.
Outlook and Projections for WP1
The outlook for WP1 is positive, as the work has been executed successfully with no significant deviations from the original research plan. Ongoing work includes the assessment of the effects of cigarette smoke extract on zebrafish eye health, the establishment of in vivo models using Optomotry response to measure visual acuity and contrast sensitivity in zebrafish of different ages, the characterization of extracellular vesicles through proteomic analysis to investigate CysLTR crosstalk in different disease models, and the evaluation of the role of CysLTs in the extracellular matrix context in uveal melanoma. These investigations will provide further insight into the novel pathological mechanisms linking CysLT signaling to diseases of the ocular, central nervous, and cardiovascular systems, as well as cancer.
Outlook and projections for WP2
The outlook for WP2 is positive, as the project has progressed according to plan with no major deviations. The main tasks moving forward include the identification and development of novel molecules that target the CysLT pathway using virtual computational drug discovery techniques. Additionally, the project will focus on the development of in vivo cancer models using rodents and zebrafish, as well as the modulation of CYSLT signaling in the extracellular matrix of Uveal melanoma to explore its potential as a therapeutic target. The goal is to gain a better understanding of the role of CYSLT signaling in the tumor microenvironment and to develop potential therapeutic interventions.
Outlook and Projections for WP3
During Period 1, WP3 of CRYSTAL3 has progressed according to plan, with all deliverables on track. The consortium has generated training material and organised a public workshop on computational drug discovery. Nine research outcomes with potential commercial exploitation have been identified, and a business plan for the commercialization of a panel of novel cancer biomarkers is being developed with the support of Horizon Results Booster Services provided by the Commission. In the upcoming months, additional secondments are planned to develop new commercial services and products, with a focus on validating and standardizing the research models developed in WP1 and WP2. Additionally, two new reviews on the role of the CysLT receptor in cancer and cardiovascular disease are being prepared for publication.
Firstly, it has facilitated the development of participating academic and non-academic institutions by promoting cross-sectoral research and innovation in Europe, enabling them to appreciate their different priorities, strategies, and management approaches while working effectively with each other. For instance, all SMEs in the consortium have grown in terms of size and turnover during this period, and several participants have been awarded new grants to expand or continue collaborations initiated in CRYSTAL3.
Secondly, the project has promoted the career development of 20 MSCA fellows who gained cross-sectoral expertise, which has accelerated their career transitions to industry or given them the confidence to return to academia to broaden their research acumen.
Thirdly, CRYSTAL3 has achieved significant scientific results, including nine peer-reviewed publications, 11 posters presented at international conferences, and all deliverables linked to technical WPs 1-3, which are discussed in more detail in the report.
Fourthly, the project has raised society's awareness of the research's impact through various outreach activities, such as the Uveal Melanoma Awareness Campaign and the Virtual School/Lab International Visits organized in 2021.
Finally, CRYSTAL3 has developed various items with significant potential for enhancing treatments and diagnostic tools for patients. For example, the consortium is working with the assistance of EU-Horizon Results Booster Services, on further validation and business plan development for a novel Panel of Cancer Biomarkers.
Outlook and Projections for WP1
The outlook for WP1 is positive, as the work has been executed successfully with no significant deviations from the original research plan. Ongoing work includes the assessment of the effects of cigarette smoke extract on zebrafish eye health, the establishment of in vivo models using Optomotry response to measure visual acuity and contrast sensitivity in zebrafish of different ages, the characterization of extracellular vesicles through proteomic analysis to investigate CysLTR crosstalk in different disease models, and the evaluation of the role of CysLTs in the extracellular matrix context in uveal melanoma. These investigations will provide further insight into the novel pathological mechanisms linking CysLT signaling to diseases of the ocular, central nervous, and cardiovascular systems, as well as cancer.
Outlook and projections for WP2
The outlook for WP2 is positive, as the project has progressed according to plan with no major deviations. The main tasks moving forward include the identification and development of novel molecules that target the CysLT pathway using virtual computational drug discovery techniques. Additionally, the project will focus on the development of in vivo cancer models using rodents and zebrafish, as well as the modulation of CYSLT signaling in the extracellular matrix of Uveal melanoma to explore its potential as a therapeutic target. The goal is to gain a better understanding of the role of CYSLT signaling in the tumor microenvironment and to develop potential therapeutic interventions.
Outlook and Projections for WP3
During Period 1, WP3 of CRYSTAL3 has progressed according to plan, with all deliverables on track. The consortium has generated training material and organised a public workshop on computational drug discovery. Nine research outcomes with potential commercial exploitation have been identified, and a business plan for the commercialization of a panel of novel cancer biomarkers is being developed with the support of Horizon Results Booster Services provided by the Commission. In the upcoming months, additional secondments are planned to develop new commercial services and products, with a focus on validating and standardizing the research models developed in WP1 and WP2. Additionally, two new reviews on the role of the CysLT receptor in cancer and cardiovascular disease are being prepared for publication.