Ongoing Horizon Europe projects

Reducing Non-Human Primates in Non-Clinical Safety Assessment: The European Initiative on Minipig and Micropig Models

Call: HORIZON-JU-IHI-2023-04-two-stage submitted for HORIZON-JU-IHI-2023-04-two-stage
Topic: HORIZON-JU-IHI-2023-04-01-two-stage
Type of Action: HORIZON-JU-RIA
Action number: 101165643
Number of participants: 27
Project website: https://www.nhpig.eu/
Role: Partner

Objective: NHPig is an Innovative Health Initiative (IHI) project based on the public-private partnership of the European Union and Europe’s health industries. Its objective is to expand, share and implement biological knowledge of mini-/micropig models with the aim to reduce non-human primates (NHPs) in non-clinical safety studies. The transnational consortium includes experts in porcine medical models, veterinary pathology, computational animal science, non-clinical science, OMICs profiling, new approach methods (NAMs), as well as bioinformatics and artificial intelligence. NHPig will i) characterise humanised minipigs, micropigs and tailored disease models, including systematic biobanking, multi-OMICs profiling, and state-of-the-art imaging modalities; ii) develop, validate and implement biosensors, medical devices, and ‘intelligent’ animal housing for automated data collection and analysis in minipig safety studies; iii) fill significant knowledge gaps in the (patho)physiology of the porcine immune system; iv) validate known toxicity and efficacy biomarkers and discover novel biomarker candidates for non-clinical safety assessment; v) overcome the shortage of laboratory tools and reagents, such as validated antibodies; vi) gain experience in using mini-/micropigs for safety testing of biologicals and new therapeutic modalities; vii) Investigate in vitro to in vivo extrapolation of liver and kidney toxicity in pigs and NHP/humans to provide a comparative link to human new approach methodologies (NAMs); and viii) provide a publicly available database and IT platform for compiling, integrating and analysing existing data in NHPs/humans with data in mini-/micropig models (existing data and data generated within the NHPig programme). The establishment of a regulatory advisory board and an ethics- and animal welfare advisory board will expedite regulatory interactions and ensure compliance with the 3R principles. NHPig will generate the scientific basis for de-selection of NHPs in non-clinical safety assessment, which is an ethical requirement and also imperative according to EU legislation.

Boosting Tendon Regeneration Network

Type of Action: COST
Action number: CA22170
MoU: 080/23
CSO Approval date: 12/05/2023
Start date: 23/10/2023
End date: 22/10/2027
Role: Working Group member

Objective: Musculoskeletal disorders/diseases are among the main causes of disability worldwide and are exacerbated by an increasingly sedentary lifestyle and ageing population. Among these, tendinopathies, account for 30-50% of musculoskeletal-related primary care visits worldwide. These diseases produce pain, swelling and restricted ranges of motion, and affect individuals across ages in their work and leisure time. The estimated costs to European Union healthcare systems are in excess of 800 M€ annually. Despite the impressive progress achieved on the development and translation of regenerative therapies for specific applications, major progress in designing and translating clinically-relevant advanced regenerative therapies for tendon is still missing. The lack of coordination and scattering of research and knowledge in the field of tendon mainly justifies the disappointing results attained so far.
The main aim of TENET Action is to create the TEndon regeneration NETwork, a scientific network of excellence mainly based in Europe integrating academics, research laboratories, clinicians, biotechnological companies, and regulatory bodies to foster the scientific and industrial capacity to develop, test and translate advanced regenerative therapies to promote tendon tissue regeneration and restoration of tendon function. This Action will bring together sufficient expertise and critical mass to produce an integrated, coordinated and multidisciplinary response to the challenges in the field. This will allow the full deployment of advanced regenerative therapies for tendon, not only to respond to open scientific questions, but more importantly to boost the clinical translation of these therapies in order to improve patient treatments and outcomes.

Boosting Resilience, Innovation and Growth in the HealTh industry through skills development

Call: ERASMUS-EDU-2024-PI-ALL-INNO
Topic: ERASMUS-EDU-2024-PI-ALL-INNO-BLUEPRINT
Type of Action: ERASMUS-LS
Action number: 101187080
Number of participants: 25
Role: Partner

Objective: The European health industry faces an unprecedented tailwind of rapid technological, economic, environmental and societal change. A resilient ecosystem relies on a trained, competent and committed talent force with the relevant skills, proficiencies and technical savviness to thrive in the post-COVID workplace and shifting sectoral landscape amidst the twin green and digital transition.
The BRIGHTskills project aims to build a critical mass for up- and re-skilling efforts in the health industry. A comprehensive, concerted, multi-stakeholder and cross-border approach will be deployed to undertake robust, continuous and forward-looking analysis of urgent and emerging skills needs in the workforce. Training programmes will be curated, designed and piloted through innovative pedagogical methodologies, while certification, accreditation and recognition frameworks will be put in place to promote wide acceptance in line with educational and industry standards and best-practices. The project will develop and deliver an actionable EU Health Industry Skills Strategy, setting a clear roadmap for expansive implementation of talent development efforts, thereby driving transformation of regional, national and European ecosystems.
BRIGHTskills brings together a consortium of 19 beneficiaries, 1 affiliated entity and 6 associated partners from 11 countries in Europe, altogether representing the voice of higher education institutions, VET providers, labour market actors, health industry enterprises, SMEs and intermediary network organisations across various disciplines and subsectors including MedTech, Digital Health, pharmaceuticals and biomanufacturing. The project will accordingly solidify the ambitions of the newly established Large-Scale Skills Partnership for the European Health Industry under the Pact for Skills.

pan-European Management of Biological toxin incidents through standaRdisAtion initiatives for Crisis response Enhancement

Call: HORIZON-CL3-2023-DRS-01
Topic: HORIZON-CL3-2023-DRS-01-03
Type of Action: HORIZON-RIA
Action number: 101168322
Number of participants: 16
Project website: https://embracebiotoxhub.eu/
Role: Partner

Objective: Biotoxins pose significant challenges to current crisis management approaches. Existing concepts of operation, derived from Chemical, Biological, Radiological and Nuclear doctrines, and Union Civil Protection Mechanism initiatives, do not address the distinctive and highly complex attributes of a biotoxin crisis. EMBRACE aims to improve Europe’s capacity to respond effectively to biotoxin incidents.
We will consolidate and apply scientific and clinical knowledge of biotoxins to revise response protocols and deliver innovative solutions specifically tailored to address gaps and needs identified in current provision. Highlights include analysis of biotoxins not previously addressed in this context, risk-based recommendations for PPE and novel decontaminants, in vitro studies to identify human biomarkers of exposure, novel samplers, portable biosensors and field diagnostics devices, and software tools to assist responders in biothreat risk assessment. To ensure intersectoral and cross-border interoperability of these solutions and successful commercialisation of our exploitable assets, we will prioritise a carefully planned standardisation and valorisation programme. EMBRACE will engage with existing initiatives and projects to create a vibrant biotoxin knowledge network; a multi-sectoral community of stakeholders, on the basis of which a sustainable Biotoxin Task Force will be established as a source of expertise and guidance on biotoxin incidents both for EMBRACE and the wider community. The network of stakeholders and EMBRACE’s ambitious programme of scientific, technological, and operational advances will be supported by the creation of a biotoxin reference and stakeholder hub designed to facilitate knowledge exchange and provide users with direct access to widely distributed and expertise. Finally, EMBRACE’s innovative sustainability strategy will ensure that its solutions and the biotoxin community continue to thrive beyond the duration of the project.

A synaptic mechanogenetic technology to repair brain connectivity

Call: HORIZON-EIC-2022-PATHFINDEROPEN-01
Topic: HORIZON-EIC-2022-PATHFINDEROPEN-01-01
Type of Action: HORIZON EIC Grants
Action number: 101099579
Number of participants: 8
Project website: https://www.synmech.eu/
Role: Partner

Objective: The SynMech project is developing a mechanogenetic technology to regulate functional connectivity of neural circuits for therapeutic purposes in brain disorders. The objective of SynMech-Hop on is to complement the original work plan with i) novel, highly translational human 2D and 3D in vitro models of epileptic seizures, ii) increase the human translational value and reduce animal use (3Rs), and iii) enhance the project innovation capacity via higher TRL levels towards clinical applicability, business development, regulatory, societal acceptance and industrial key stakeholder communications. Our ambition is to use in vitro neural models derived from human induced pluripotent stem cells (hiPSCs) to evaluate biosafety and efficacy for epilepsy of synaptic mechanogenetics. BIOT provides a wide variety of human in vitro methodologies, which could complement the excellence of SynMech technologies by generating standardized in vitro human epilepsy models with the use of patient-derived iPSCs and epileptic seizure-inducing drugs, and thus fill current scientific gaps. Induced seizures can be used to effectively address human in vitro seizure-liability testing because they allow us to define both electrogenic and non-electrogenic aspects of epilepsy in a spatiotemporal fashion, enabling the assessment of the efficacy and biocompatibility of SynMech technology components (functionalized biocompatible magnetic nanoparticles, bioengineered synaptic mechanosensors and magnetic stimulators). We will assess efficacy and safety of synaptic mechanogenetics as an antiepileptic treatment in human 2D and 3D in vitro models, comparing it to established pharmacological anticonvulsant approaches. This will allow SynMech partners to add an additional layer of interdisciplinarity and integrate BIOT’s in vitro solutions to replace some animal experiments (3Rs) and to enhance industrial and medical translatability, underpinning SynMech’s innovations towards higher TRLs.

Novel brain health solutions across four focus areas: Prevention and care, Methods and data, Innovation and society, and Ethics and well-being

Call: MSCA COFUND 2024
Topic: HORIZON-MSCA-2024-COFUND-01-01
Type of Action: TMA-Cofund-Postdoctoral
Action number: 101179145
Number of participants: 37
Role: Associated partner

Objective: The NOVEL Postdoctoral Programme pioneers in merging diverse socio-cultural and scientific expertise to forge new brain health solutions, energizing regional, national and global development. It integrates neuroscience, data science, innovation management, and social and legal studies across four synergetic research areas: Prevention and Care, Methods and Data, Innovation and Society, Ethics and Wellbeing. This initiative thrives on cooperation with companies, health organizations, patient groups, and universities, offering a rich training blend through compulsory non-academic secondments, mentoring, and dynamic summer schools. Targeting under-represented and minority scientists across different disciplines, NOVEL encourages applicants to work on their research projects within an inclusive community-based platform, ensuring equal opportunities. The merit-based selection process is transparent, conducted by external international assessors.

NOVEL’s training goals are multifaceted: nurturing research excellence and inclusivity, fostering broad intersectoral networks, embracing Open Science, and aspiring to be a global benchmark in brain health research training. The training is structured into three pillars: enhancing disciplinary skills, developing transferable competencies in innovation, management, leadership, and ethics, and boosting active parnerships and stakeholder engagement. Mandatory and optional secondments with NOVEL partners underscore its comprehensive intersectoral approach. The programme promises attractive employment conditions, including 36-month contracts, competitive compensation, strong local support systems, and an inspiring environment for research and collaboration. Each fellow receives guidance from multiple supervisors and a mentor, facilitating both conventional and innovative career trajectories, positioning NOVEL at the forefront of research training in brain health.

Toward consolidation of germplasm and cell reversible drying through knowledge transfer

Call: HORIZON-MSCA-2022-SE-01
Type of Action: HORIZON-TMA-MSCA-SE
Action number: 101131087
Number of participants: 7
Role: Participant

Objective: WhyNotDry will deepen our knowledge on reversible drying in cells and germplasm toward the development of a dry biobanking as an alternative to the current freezing in Liquid Nitrogen (LN). LN is expensive, requires dedicated facilities and power supply, and has a high CO2 footprint. WhyNotDry will achieve its aims through a multidisciplinary, intersectoral, international network of scientists that will: i) Develop a drying/rehydration platform using naturally desiccation-tolerant midge (Polypedilum vanderplanki) Pv11 cell lines; ii) Identify the best combination of naturally occurring xeroprotectants (xero=dry) from desiccation-tolerant insect cell line and the best performing water subtraction platform. iii) To use the best xeroprotectants mix and the drying/rehydration protocol for mammalian cells/germplasm. vi) Develop a prototype for controlled dehydration of microvolumes of cell. The R&I activities leading to these aims will be carried out by knowhow sharing through Staff Exchanges between: 3 EU academies, 2 EU SMEs, 2 international partners (Japan, Thailand). Outcomes of WhyNotDry will be incorporated into a cheap, environmentally friendly, and easy biobanking for biodiversity conservation, assisted reproduction, stem cell/personalized medicine. Successful development of this technology will set the basis for a radically new, ‘green’ biobanking paradigm, simplifying the maintenance and shipping practices in life sciences, with enormous reduction in costs and carbon footprint. Moreover, knowledge generated in WhyNotDry would be applicable to other fields such as agriculture, environmental science, food processing, and the pharmaceutical industry, where elective or enforced (by climate change) drying is dealt with. Finally, WhyNotDry will empower young scientists with transferable skills, ensuring career prospects in academia/industry, and strengthen the international/sectorial network between disciplines, boosting European excellence.

Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

Type of action: COST
Action number: CA20121
MoU: 061/21
CSO Approval date: 25/05/2021
Start date: 19/10/2021
End date: 18/10/2025
Role: Management Committee member and Working Group member

Non-communicable diseases (NCDs) such as cancer, diabetes, cardiovascular, neurodegenerative, respiratory or immune diseases, account for 77% of all deaths in Europe and remain the most prevalent and without effective therapy. Networking among multidisciplinary teams that explore disease from a perspective of causative pathomechanisms rather than clinical symptoms is the most appropriate approach to overcome this problem. Such pathomechanisms imply the loss of homeostatic functions leading to the pathologic formation of reactive oxygen species, chronic inflammation, metabolic unbalance and proteinopathy. The transcription factor NRF2 is a master regulator of multiple cytoprotective responses and a key molecular link among many NCDs. It provides a unique strategy for drug development and repurposing that is now starting to be translated to the pharmacological and clinical arena. This Action will build a network of excellence for integrating and spreading the existing knowledge and providing innovative services, drugs and tools related to NRF2-pharmacology, with the final goal of boosting the translation to the European industry sector. To achieve this, the Action has already gathered a wide set of professionals from different disciplines (medical chemistry, pharmacology, clinical research, molecular biology, bioinformatics, etc.) and sectors (universities, research centres, hospitals, biobanks, biotech SMEs and pharma companies, etc.). The Action will expand among COST countries IPCs and NNCs, will actively involve SMEs and ECIs, and will respect gender balance.Thanks to COST tools the Action will boost the career of young researchers, wide participation (especially from ITC countries), and spread excellence.

Generation of human induced pluripotent stem cells from HAPLO-selected cord blood samples

Type of action: COST
Action number: CA21151
MoU: 065/22
CSO Approval date: 27/05/2022
Start date: 11/10/2022
End date: 10/10/2026
Role: Management Committee member and Working Group co-leader

HAPLO-iPS aims to create a collaborative network to provide a framework for hiPSC generation of hiPSC homozygous for frequent HLA haplotypes, compatible with a significant percentage of the population to be used for cell therapy clinical trials and to create a data collection system (REGISTRY) for such lines.
HAPLO-iPS will establish an European-based excellence network on hiPSC-derived cell-based medicines that not only will boost the state-of-the-art of this research field if not will also contribute to Europe worldleadership through the medical, scientific, economic, and social development of Europe and strengthening Europe’s competitiveness capacities. This network includes all the relevant stakeholders: hiPSC generation/banking centres, CB banks that will supply cord blood units; manufacturing centres (GMP complying), immunology experts, chemistry and manufacturing controls, regulatory bodies, National Agencies, and ethics experts. The challenge will be approached essentially by networking with all the stakeholders involved sharing knowledge, standardizing methodology and developing an educational training programme for researchers.
HAPLO-iPS is also promoting the participation of researchers from less research-intensive countries as a significant percentage of the members are from ITC countries. ITC participants will have access to research facilities, training courses, mentoring of ITC young researchers and will participate spreading excellence and widening participation programme. Furthermore, Key leadership positions in the Action Management are reserved to COST ITC.
Overall, this action will pioneer new approaches that will foster the progress of a haplo-selected hiPS generation of therapeutics by the development, implementation and exploitation of a registry with all the information for the benefit of patients.

The role of immunity in tackling Parkinson’s Disease Through a Translational Network

Type of action: COST
Action number: CA21117
MoU: 031/22
CSO Approval date: 27/05/2022
Start date: 20/09/2022
End date: 19/09/2026
Project website: https://immuparknet.eu/about/
Role: Management Committee member and Working Group member

Parkinson’s disease (PD) is a widespread chronic disease affecting 600 000 people in the EU. It has no cure, hence patients rely only on symptomatic treatments. By consequence PD relentlessly results in serious disability, poor quality of life for patients, families and caregivers, causing high individual and societal costs. PD etiology is largely unexplained and several pathogenetic hypotheses have been explored. The role of the immune system has been suggested by important studies, showing significant changes in both central and peripheral immunity. Several approaches exist to target the immune system, thus – would the contribution of immunity in PD be clarified – novel therapeutics could be developed. Currently only few research groups study the role of the immune system in PD; however methodological and technical approaches are highly variable. Moreover, networking and exchange of expertise between groups working on immunity in different pathologies is still underdeveloped, with the consequence that precious advances are not fully exploited or even precluded. The sharing of experiences, also taking advantage of the efforts made in similar neurodegenerative conditions, will provide unprecedented advantages.
IMMUPARKNET focuses on such challenges and aims at establishing an innovative, multi-interdisciplinary Network, fostering exchange of expertise among outstanding experts, from different countries and institutions, involving scientists studying immunity in PD but also immunity in other neurodegenerative diseases. IMMUPARKNET will thus establish a first nucleus of a multidisciplinary ecosystem to fight the fragmentation of efforts and approaches, both in research and clinical practice, for boosting research towards the development of innovative treatments for PD.

Genome Editing to Treat Humans Diseases

Type of action: COST
Action number: CA21113
MoU: 027/22
CSO Approval date: 27/05/2022
Start date: 15/09/2022
End date: 14/09/2026
Project website: https://www.genehumdi.eu/
Role: Management Committee member and Working Group member

Recent advances on genome editing (GE) technologies have opened the possibility of treating diseases through precise modifications of patients’ genomes. Impressive results have been achieved on animal models of several genetic disorders, infectious diseases as well as cancer and several clinical trials are already on going. However, the inadequate integration of the results of academic research into the research development strategy of pharmaceutical companies, the insufficient interest of academic institution in regulatory science and the absence of established standards to well acceptable risk-benefit ratio by regulatory agencies, preclude its general application for treating human diseases. Therefore, the translation of the GE technologies to address public health needs, require a strong collaboration between basic and clinical research, regulatory bodies and the different stake holders involved for each application. There are several networks to improve or analyse GE technologies for different applications,
however, no one cover all the actors involved in gene therapy translation. The principal aim of the GenE-HumDi Action is to bring together pharmaceutical companies, academic institution, science and regulatory agencies, biotechnology firms, patient advocacy association and information technology, in order to tackle knowledge fragmentation with the aim to accelerate the translation of GE technologies to the treatment of human diseases.

Medicine made to measure

Call: MSCA Doctoral Networks 2022 (HORIZON-MSCA-2022-DN-01)
Type of Action: HORIZON-TMA-MSCA-DN
Action number: 101120256
Number of participants: 22
Role: Participant

Objective: Modern medicine seeks to personalize diagnosis and treatment to the needs of individual patients. This need is heightened in particular for those individual patients where no treatments are available – and where current standard treatment development paradigms exclude to generate such. The ultimate goal of Medicine made to Measure (MMM) is to go even beyond the latest genetic medicine approaches, implementing a novel paradigm of treatment development: the field of single patient tailored antisense oligonucleotide (ASO) treatments for patients with nano-rare disease mutations. Specifically, MMM will develop core modules of a novel “out-of-the-box”, but still EMA-advised treatment development path for these patients – from omics-based theranostics, via preclinical target validation to innovative trial methodology and a pioneering ethical framework for individualised genetic therapies. MMM provides a unique opportunity for doctoral candidates to be involved in building – and to receive training – in all core modules needed for tailored ASO treatment in Europe. This new scientific field requires a new generation of open-minded, technology-fluent and applications-oriented experts.

MMM will help educate future drug development and translational experts in adopting and disseminating such a cross-specialty approach. Our idea for this innovative training network is built on our personal experience and understanding of the importance of single patient tailored genetic treatments in the years to come. We propose a consortium of world-leading experts and partners that present with extended experience and relevant know-how in molecular biology, neurology, translational medicine, biochemistry, bioinformatics, philosophy, mathematics, regulatory science and engineering. Thus, MMM provides an exceptional platform to young, ambitious and talented researchers who like to engage in supporting the concept of single patient tailored treatments.

Targeting Circadian Clock Dysfunction in Alzheimer’s Disease

Call: HORIZON-MSCA-2021-DN-01
Type of Action: HORIZON-TMA-MSCA-DN-JD HORIZON TMA MSCA Doctoral Networks – Joint Doctorates
Action number: 101072895
Number of participants: 24
Role: Associated partner

Objective: Recent Nobel Prize-winning discoveries on circadian clock (CC) have laid the foundation for ground-breaking approaches to treat many diseases, including Alzheimer’s disease (AD). AD is a current public health priority. Amplifying the demographic burden of the rising numbers of patients is the low success rate of AD therapies. Given that CC genes regulating memory, sleep, and neurodegeneration have altered expression profiles in AD, CC has recently emerged as a viable therapeutic target for new effective drugs. However, how to develop them remains a fundamental challenge. The “Targeting Circadian Clock Dysfunction in Alzheimer’s Disease” Doctoral Network (TClock4AD) is proposed to create a new generation of researchers able to face such challenge by harnessing neurobiology, medicinal chemistry, pharmaceutical nanotechnology, neuroimmunology, big data, bioinformatics, and entrepreneurship. TClock4AD will exploit unique expertise and advanced technologies at 10 leading universities, 3 research centers, a hospital, 10 non-academic institutions including SMEs, a large pharma company, a Health industry association, and a patient organization across EU, UK, Israel, USA and China. TClock4AD will deliver double degrees to 15 doctoral candidates, with triple-i knowledge/skills, broad vision and a business-oriented mindset. Their research activities will be structured around 5 scientific themes to: (1) develop novel artificial intelligence-, proteolysis targeting chimeras- and multitarget-based strategies for new CC drug candidates (2) develop novel drug delivery nanotechnologies, which take into consideration CC (3) investigate innovative in vitro (stem-cells, 3D cultures) & in vivo (Drosophila), as well as organ-on-chip techniques, for preclinical validation of CC drugs (4) get insight into the molecular mechanisms underlying CC in AD and associated drug response in mice and C. elegans models (5) develop innovative biotech business model and exploitation strategies.

Unveiling the molecular basis of chromatinopathies to delineate innovative therapeutic solutions

Call: HORIZON-MSCA-2021-DN-01
Type of action: HORIZON-TMA-MSCA-DN HORIZON TMA MSCA Doctoral Networks
Action number: 101073334
Number of participants: 14
Role: Associated partner

Objective: Chromatinopathies (CPs) are a group of rare genetic diseases, which share clinical features as well as causal genetic alterations, leading to the inactivation of chromatin regulators involved in gene expression control and 3D chromatin organization. Within the framework of Chrom_Rare, we will focus on a group of clinically well-defined CPs, including Kabuki Syndrome, Charge Syndrome, Rubinstein-Taybi Syndrome and Cornelia de Lange Syndrome. Although the causative genes for these CPs have been identified, the consequences of their inactivation both at the molecular and functional level, have not been defined. The clinical features of CPs vary widely, suggesting that the impact of the haploinsufficiency of the affected chromatin regulators could depend on the epigenetic state and/or interactions with additional genetic and environmental factors. Hence understanding the genetic and epigenetic determinants of CPs represent an immediate medical need, as this will ultimately facilitate reaching the development of new therapeutic approaches. Our main goal is to set-up an intra-sectoral, cross-disciplinary training programme that would prepare the next generation of researchers equipped with advanced theoretical, technical and computational skills to study fundamental aspects of chromatin biology and their impact on CPs. In parallel, Chrom_Rare will devise new strategies to translate the molecular findings into new diagnostic and therapeutic approaches for patients affected by CPs. To enable understanding the molecular basis of chromatinopathies, we aim at developing multiple disease models recapitulating the main clinical features of CPs (WP1), investigating the genetic, epigenetic and topological determinants of CPs (WP2) and uncovering perturbed regulatory circuitries suitable for therapeutic intervention (WP3). Overall Chrom_rare will address unmet socio-economic, medical and scientific needs, for the understanding and possible treatment for CP.

Ongoing H2020 projects

Neurodevelopmental ciliopathies: a multimodel approach from molecular mechanisms to patients
variant interpretation and treatment strategies

Call: JTC2021 – Neurodevelopmental Disorders
Type of research: ERA-NET NEURON (Neurological and Mental Disorders)
Logo: under development
Number of participants: 6
Role: Partner
Reference Number: NEURON_NDD-120d
Project website: https://ndcil.eu/

Objective: Neurodevelopmental abnormalities resulting in life-long disability are a major feature of inherited ciliopathy disorders. Primary cilia are found on most cell surfaces, including neurons, and play key signalling roles during development. However, little is known about ciliary function/dysfunction in the brain, and no curative strategies exist for these disorders. Moreover, several patients carry “variants of unknown significance” (VUS), whose pathogenic impact on disease mechanisms remains unknown. To address these shortfalls, NDCil will focus on four major genes causing the archetypal neurodevelopmental ciliopathy, Joubert Syndrome (JS), and will employ complementary in vitro models (mouse embryonic stem cells, patient-derived induced pluripotent stem cells undergoing 2D and 3D differentiation towards cerebellar neurons and astrocytes) and in vivo models (C elegans, zebrafish) and wide-ranging techniques (CRISPR, proteomics, transcriptomics, live cell imaging, high throughput drug screening) to characterize and compare a wealth of variants (mainly VUS), identified in JS patients. Aims of NDCil are: i) to increase knowledge of cilia in neural development and disease at multiple scales (from the subciliary TZ compartment to neurons, to the whole brain); ii) to correlate specific patients’ mutations with JS mechanisms and improve VUS interpretation; iii) to explore novel therapeutic approaches via drug repurposing strategies. Together, our interdisciplinary consortium of five partners provides a platform for assessing and remedying the effects of specific mutations on neurodevelopment processes, with expected benefits on diagnosis, prognosis and counselling.

Defining (sex and age) cell-specific epigenetic mechanisms underlying Environmental Enrichment/Exercise as non-pharmacological intervention for Alzheimer’s and Huntington’s disease and related potential noninvasive biomarkers

Call: Understanding the mechanisms for non-pharmacological interventions (2022)
Type of research: ERA-NET JPND (EU Joint Programme – Neurodegenerative Disease Research)
Logo: under development
Number of participants: 8
Role: Partner
Reference Number: JPND2022-115

Objective: Aerobic exercise or cognitive training, as well as the combination of both (referred to as environmental enrichment, EE) can enhance synaptic plasticity, improve memory function and ameliorate disease phenotypes in animal model for age-associated neurodegenerative diseases, such as Alzheimer’s disease (AD) and Huntington’s disease (HD). Similar observations have been made in humans, in both healthy individuals and patients and the applicants have contributed to both lines of research. Given that epigenetic regulations are central to the integration between environmental and genetic factors, we hypothesize that they are critical in conveying environmental therapies into beneficial effects. Epigenetic changes associated with AD and HD have been extensively characterized in mouse models and in human patients’ brains, including by the applicants. However, the role of epigenetic mechanisms in beneficial effects of environmental enrichment and exercise has remained largely unexplored. Particularly, the role of the non-coding RNAs could represent excellent biomarkers of environmental and exercise impact on the epigenome, since they may be detected in blood samples or Extracellular Vesicle (EV)-enriched fractions. In this project, we propose to elucidate the mechanisms that underlie EE and Exercise as a non-pharmacological intervention towards age-associated dementia and test specifically the hypothesis that epigenetic changes to brain cells play a key role. In a first aim, AD and HD mouse models undergoing EE and/or Exercise will be used to lead cell-type specific multi-omics (genome-wide analyses of chromatin and transcriptional modifications) and build computational regulatory models in the context of chromatin dynamics in two brain regions affected by the diseases, further identifying non-coding (nc)RNAs as biomarker candidates for efficient therapy. Behavior and brain MRI will attest for beneficial effects of such stimulation. Epi-editing approaches will bring mechanistic insights. The second aim is designed to translate our data to human searching for a noninvasive candidate ncRNA biomarkers isolated from blood samples of AD and HD patients (collaboration with neurologists), that could be relevant of successful EE and/or exercise strategy. Further, enrichment of ncRNA biomarker candidates will be assessed in specific circulating extracellular vesicles from the plasma. Lastly, selected RNA markers will be tested for their ability to reproduce identified epigenomic changes in human-derived cellular systems and further validated in new cohorts of patients. By providing insights in molecular/cellular, sex and age-dependent mechanisms underlying non-pharmacological interventions such as EE/Exercise in main brain regions affected by AD and HD, our data will offer novel opportunities for medicine personalization. Defining the specific epigenetic response to EE/Exercise and a mean for its biological tracing will bring further opportunities to define new therapeutic strategies or use combinatorial therapeutic strategies supporting non-pharmacological ones (epi-drugs or RNA-based therapeutics).

ElectroMechanoActive Polymer-based Scaffolds for Heart-on-Chip

Call: H2020-NMBP-TR-IND-2018-2020
Number of Participants: 10
Role: Partner
Action number: 953138
Project website: https://emaps-cardio.eu/

Objective: Cardiovascular diseases (CVDs) account for 45% of deaths in Europe and are estimated to cost the EU economy €210 billion a year. However, only four drugs targeting cardiovascular diseases have been approved for use in the last decade. Thus, models that could effectively simulate diseased tissues, would enable the accurate assessment of the efficacy of the pharmaceuticals, and would accelerate drug development are urgently needed. The main bottleneck towards such models is the foetal-like state of the human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs). That is hiPSC-CMs do not reach adult-like maturity. The objective of this project is to produce a platform for growth and maturation of cardiac microtissues for adult-like organotypic models in healthy and diseased states. To achieve that, biomimetic microenvironment that provides all the needed stimuli (electrical, mechanical, topological (3D environment) and biochemical (release of active molecules)), during the maturation of hiPSC-CMs will be developed. This will be achieved by combining electromechanoactive polymer-based scaffolds (EMAPS) with bioactive membranes. To characterize the effects of CVD drugs, the contractility of the microtissue will be monitored continuously and simultaneously (over 24-wells) using the sensors developed during the project. To increase the sensitivity and accuracy of the model, deep-learning based algorithms to detect the effects of drugs in vitro will be developed and verified. The goals will be achieved by a multidisciplinary consortium with complementary know-how of three academic units and seven small companies. The increased sensitivity and accuracy of organ-on-chip devices is a needed leap in technology that will accelerate new drug development without the need for animal models; the project aims to provide a platform for the realization of such physiologically-relevant organotypic models.

European consortium for communicating gene- and cell-based therapy information

Call: H2020-SC1-BHC-2018-2020
Number of Participants: 49
Role: Partner
Action number: 965241
Project website: www.eurogct.org

Objective: The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT) unites 49 partner organisations and institutions across Europe, including the major European advanced therapies learned societies, with the common goal of providing reliable and accessible information related to cell and gene therapy development to European stakeholders. EuroGCT has two major objectives:

• To provide patients, people affected by conditions, healthcare professionals and citizens with accurate scientific, legal, ethical and societal information and with engagement opportunities, and thus to support better informed decisionmaking related to cell and gene-based therapies.
• To facilitate better decision-making at key points in development of new therapies and thus enable improved product development, by providing the research community and regulatory and healthcare authorities with an information source on the practical steps needed for cell and gene therapy development.

To achieve our aims, EuroGCT will adopt a highly structured system for coordinated management of information related to cell and gene therapy development and, from this, will implement an ambitious programme of online and direct stakeholder information provision and engagement. All outputs will be delivered in 7 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading cell and gene therapy-related organisations and basic and clinical research labs across Europe, including new member states; together with experts in product development, ethical, legal and societal issues, and in evaluating clinical outcomes; patient representatives; and science communicators. It thus is uniquely placed to develop a world-leading cell and gene therapy information resource and to meet the challenge outlined in Topic SC1-HCO-19-2020.