11e édition des AFSSI Connexions

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Posters scientifiques2024-07-22T15:13:21+02:00

Session Posters

Découvrez les posters scientifiques présentés lors de cette 11ᵉ édition des AFSSI Connexions

Les AFSSI Connexions sont l’occasion de découvrir les innovations proposées par les membres de l’AFSSI
Les entreprises partenaires de vos projets de R&D

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Un jury d’experts

François CAUSSADE

Président & CEO

ANS Biotech

Anne JOUVENCEAU

Coordinatrice

Oliver LOGET

Président & CEO

Susanna MALMSTRÖM

Directrice Alliances

CILcare, lauréat du prix du jury

Sensorineural hearing loss as a complication of type-2 Diabetes mellitus: evidence of several cellular and neural impairments.

CILcare, lauréat du prix du jury aux AFSSI Connexions 2024

En gagnant le prix du jury, CILcare remporte :

  • Un accès membre Village AFSSI d’une valeur de 690€HT pour la prochaine édition
  • Une prise de parole lors de la soirée networking
  • Une mise en visibilité sur les canaux AFSSI

Abstract

Carolanne COYAT1*, Karine TOUPET1*, Gaëlle NAERT1*, Sylvie PUCHEU1* and Mathieu SCHUE1*.

  1. Cilcare SAS, 34080 Montpellier France

While retinopathy, nephropathy, and peripheral neuropathy are well-established complications of type 2 diabetes, sensorineural hearing loss is increasingly recognized as a comorbidity of this metabolic disease. Several causes have been suggested, including auditory peripheral neuropathy (synaptopathy), which can lead to early-onset hearing loss. No extensive research has been conducted on preclinical models of type 2 diabetes. Our study aims to better characterize the development of SNHL concomitantly with diabetes biomarkers in a diabetic mouse model.

Genetically modified mice with mutations in the leptin receptor gene (BKS(D)-Leprdb/JOrlRj)2 were monitored from 5 to 13 weeks of age to assess the parameters of their diabetes (blood glucose, glycosylated hemoglobin, biochemical analyses) and their hearing, using auditory evoked potentials and terminal histological analyses of the cochlea.

In this model, Leprdb/Leprdb mice exhibited a phenotype of obesity and hyperglycemia, with fasting blood glucose levels of ~4 g/L compared to 2 g/L in heterozygous control mice. Diabetic mice displayed early-onset hearing loss characterized by a significant increase of auditory brainstem response (ABR) thresholds and a significant decrease of distortion product otoacoustic emission (DPOAE) amplitudes compared to the Leprdb/+ control mice. These data correlated with morphological and histological changes in the cochlea.

Here, we present data from a murine model illustrating the detrimental consequences of type 2 diabetes on hearing. This translational preclinical model may be useful for evaluating the efficacy of drug candidates for the preservation and restoration of hearing in type 2 diabetic patients.

Atlantic Bone Screen et Enterosys, lauréats du prix du public

Décrypter l’Axe Intestin-Articulation : Vers de Nouvelles Stratégies Thérapeutiques ou Préventive pour l’Obésité

Atlantic Bone Screen et Enterosys, lauréats du prix du public aux AFSSI Connexions 2024

En gagnant le prix du public, Atlantic Bone Screen et Enterosys remportent :

  • Une prise de parole lors de la soirée networking
  • Une mise en visibilité sur les canaux AFSSI

Abstract

Dans le contexte de la prévalence croissante de l’obésité et de ses comorbidités, la compréhension des interactions entre l’intestin et les articulations devient cruciale. Enterosys, spécialiste de la communication entre l’intestin et les organes périphériques, en collaboration avec Atlantic Bone Screen, expert en recherche préclinique dans les pathologies osseuses et articulaires, propose une offre de service intégrée pour étudier l’axe intestin-articulation. Cette approche innovante vise à explorer le potentiel thérapeutique de nouveaux actifs dans le traitement des pathologies ostéo-articulaires associées à l’obésité.

Nous avons utilisé un modèle murin, des souris C57BL6J mâles de 9 semaines, soumises à un régime hyperlipidique à 60% pour induire l’obésité. L’étude s’est focalisée sur l’évaluation de divers paramètres : métaboliques (gain de poids, test oral de tolérance au glucose, profils lipidiques plasmatiques, poids des tissus adipeux), intestinaux (marqueurs de la fonction de barrière et perméabilité, analyses histologiques) et articulaires (analyses morphologiques par microtomographie (µCT) et histopathologiques).

Les résultats montrent des modifications significatives des paramètres métaboliques et des altérations des marqueurs de la fonction de barrière intestinale.  Des signes d’inflammation et d’atteintes au niveau ostéoarticulaire peuvent être aussi observés, soulignant l’impact de l’obésité sur la santé ostéo-articulaire.

Cette étude met en évidence le potentiel de l’axe intestin-articulation comme cible thérapeutique dans les pathologies métaboliques et dégénératives. Notre offre de service conjointe permettra d’offrir une solution complète pour l’évaluation de l’efficacité d’actifs dans un cadre préclinique, promouvant une approche holistique dans la gestion de l’obésité et ses comorbidités articulaires.

Découvrez les sociétés qui ont soumis un poster scientifique afin de promouvoir leurs recherches

ANS Biotech

Evaluation of analgesic efficacy and adverse effects of new pain treatments: set up of an innovative package ALGOGramTM / ADVERSAFE.

Maffre V., Darbaky Y., Clavier L., Chassaing T., Jonchère M., Decombas L., and Diop L.

ANS Biotech, Biopôle Clermont Limagne, Site de Riom La Varenne, Riom, France

Aim of Investigation:

20-30% of population suffers from chronic pain. Pain treatments present analgesic effects associated to adverse effects which could be disabling. Pharmaceutical research needs new compounds with reduced side effects. For this reason, we have developed an innovative package including pain and adverse effect evaluation using ALGOGramTM and Adversafe.

Methods:

In order to increase the decisional power of ALGOGramTM, previously presented (AFSSI Connexion 2023), it was associated to a new tool named Adversafe. It is a package of 8 tests/parameters representative of major adverse effects observed with the currently used analgesics such as sedation, decrease in intestinal transit, ulcer or decrease in the body temperature.

To validate the package, various reference drugs classically used in clinical pain practice (morphine, pregabalin, duloxetine, acetaminophen and diclofenac) were evaluated. Results are expressed for each group as 2 dashboards illustrating analgesic efficacy and major adverse effects.

Results: Reference compounds show different analgesic profiles and adverse effects related to their pharmacological class. Opioids for example showed a decrease in intestinal transit while gabapentinoids showed sedation and ulcers were evidenced with NSAIDs.

Conclusions:

The package ALGOGram and Adversafe provides a rapid and predictive evaluation of investigational compounds in 11 different pain models/tests, enabling their prioritization for fully powered studies and an overview of the adverse effects.  In summary, this combination is a relevant decision making guide to select new analgesics devoid of major adverse effects. Interestingly, the use of a limited number of animals for both tools is an excellent way of reducing the number of animals required (3Rs approach).

Key words: pain, adverse effects, screening, rat, neuropathic pain, pregabalin, opiates

Décrypter l’Axe Intestin-Articulation : Vers de Nouvelles Stratégies Thérapeutiques ou Préventive pour l’Obésité

Dans le contexte de la prévalence croissante de l’obésité et de ses comorbidités, la compréhension des interactions entre l’intestin et les articulations devient cruciale. Enterosys, spécialiste de la communication entre l’intestin et les organes périphériques, en collaboration avec Atlantic Bone Screen, expert en recherche préclinique dans les pathologies osseuses et articulaires, propose une offre de service intégrée pour étudier l’axe intestin-articulation. Cette approche innovante vise à explorer le potentiel thérapeutique de nouveaux actifs dans le traitement des pathologies ostéo-articulaires associées à l’obésité.

Nous avons utilisé un modèle murin, des souris C57BL6J mâles de 9 semaines, soumises à un régime hyperlipidique à 60% pour induire l’obésité. L’étude s’est focalisée sur l’évaluation de divers paramètres : métaboliques (gain de poids, test oral de tolérance au glucose, profils lipidiques plasmatiques, poids des tissus adipeux), intestinaux (marqueurs de la fonction de barrière et perméabilité, analyses histologiques) et articulaires (analyses morphologiques par microtomographie (µCT) et histopathologiques).

Les résultats montrent des modifications significatives des paramètres métaboliques et des altérations des marqueurs de la fonction de barrière intestinale.  Des signes d’inflammation et d’atteintes au niveau ostéoarticulaire peuvent être aussi observés, soulignant l’impact de l’obésité sur la santé ostéo-articulaire.

Cette étude met en évidence le potentiel de l’axe intestin-articulation comme cible thérapeutique dans les pathologies métaboliques et dégénératives. Notre offre de service conjointe permettra d’offrir une solution complète pour l’évaluation de l’efficacité d’actifs dans un cadre préclinique, promouvant une approche holistique dans la gestion de l’obésité et ses comorbidités articulaires.

Comparison of preclinical Safety Assessment of NCE and Vaccines/Biologics

Olivier Loget, CapEval Pharma

Abstract

The main objective of preclinical studies for new therapeutics/prophylactics consists of assessing if these are sufficiently safe for starting first clinical trials and for evaluating their efficacy. Such preclinical experiments investigate tox/potency/immunization. We focus on safety (tox) assessment according to GLP for NBE and vaccines and compare them to NCE.

These are most often GLP studies generally carried out in selected lab species. According to animal welfare laws (3R), there is a tendency to restrict their use. Nevertheless, MoA of new entities like vaccines/NBE is complex. Therefore, animal experimentation is generally the only way to evaluate safety. Consequently, animal studies could possibly be reduced but not avoided. We are not yet in an “animal-free” R&D era.

Vaccine safety is crucial because these are often used in infants.

This is a time-consuming global development with 1-5 years for initial research phase, which is followed by clinical and pharmaceutical developments.

In general, 15-20 years are necessary before licensure, with exceptions (slower or more difficult developments happen).

For example, against malaria, development lasted much longer (research>30years>30candidates assessed) but it could also be faster in case of urgent development, like emerging infectious diseases/novel pandemic pathogens (COVID-19 is an example).

As a consequence, we have to consider needs to be vigilant and well prepared for urgent developments, particularly for vaccines, focusing on crucial investigations, for all development phases, including safety, as shown during recent pandemics (COVID-19). This is an additional proof, if necessary, that the scientific community has to implement what was learnt during COVID-19 pandemic and, to be more precise, to improve not only scientific, but more specifically global communication.

Optimising embryology protocols : combining methodologies to reduce both turnaround times and number of animals required

  1. Mancip, E. Loheac, L. Chancrin, B. Rabany, M. Esmonin, H. Kapfer, H. Rubat du Merac, L. Lopez, M. Verrier; J. Cozzi, J.Datin

In the mouse model, embryology (cryopreservation, rederivation, lineage expansion, etc.) and transgenesis services are mainly based on the use of pre-implantation embryos. The production and genetic modification of these embryos are still frequently carried out in vivo using sexual reproduction strategies (mating of animals with genotypes of interest). However, mating failures and the variability of fertilisation rates as a function of genetic background and environmental conditions (type of housing, season, food, noise, age of animals, etc.) lead to significant variability in results and prevent optimisation of animal resources. In addition, some processes require animals to be bred over several generations, which means that projects take a particularly long time to complete. The Charles River European Embryology Platform has been working continuously for several years to develop alternative in vitro procedures to sexual reproduction. Here we present some of the solutions that have been put in place and the benefits obtained in terms of reducing the number of animals used and project completion times.

Sensorineural hearing loss as a complication of type-2 Diabetes mellitus: evidence of several cellular and neural impairments.

Carolanne COYAT1*, Karine TOUPET1*, Gaëlle NAERT1*, Sylvie PUCHEU1* and Mathieu SCHUE1*.

  1. Cilcare SAS, 34080 Montpellier France

While retinopathy, nephropathy, and peripheral neuropathy are well-established complications of type 2 diabetes, sensorineural hearing loss is increasingly recognized as a comorbidity of this metabolic disease. Several causes have been suggested, including auditory peripheral neuropathy (synaptopathy), which can lead to early-onset hearing loss. No extensive research has been conducted on preclinical models of type 2 diabetes. Our study aims to better characterize the development of SNHL concomitantly with diabetes biomarkers in a diabetic mouse model.

Genetically modified mice with mutations in the leptin receptor gene (BKS(D)-Leprdb/JOrlRj)2 were monitored from 5 to 13 weeks of age to assess the parameters of their diabetes (blood glucose, glycosylated hemoglobin, biochemical analyses) and their hearing, using auditory evoked potentials and terminal histological analyses of the cochlea.

In this model, Leprdb/Leprdb mice exhibited a phenotype of obesity and hyperglycemia, with fasting blood glucose levels of ~4 g/L compared to 2 g/L in heterozygous control mice. Diabetic mice displayed early-onset hearing loss characterized by a significant increase of auditory brainstem response (ABR) thresholds and a significant decrease of distortion product otoacoustic emission (DPOAE) amplitudes compared to the Leprdb/+ control mice. These data correlated with morphological and histological changes in the cochlea.

Here, we present data from a murine model illustrating the detrimental consequences of type 2 diabetes on hearing. This translational preclinical model may be useful for evaluating the efficacy of drug candidates for the preservation and restoration of hearing in type 2 diabetic patients

HCLPearls® with differentiated HepaRG®: a new liver model for ADME-Tox applications

Laura Montagne1, Nicolas Audureau1, Arnaud Rul1, Raphaël Durand1, Zahia Hamidouche1, Jérôme Caron1, Léo Chamayou1

1 CYPRIO SAS, R&D Department, Romainville, FRANCE

While primary human hepatocytes remain the cell type of choice for several ADME-Tox studies they come with several disadvantages: their scarcity and heterogenous quality means sourcing can be a problem. Furthermore, each donor specificities can lead to unreliable results. To circumvent these drawbacks, one can use differentiated HepaRG® cells which maintain stable hepatic functions close to primary human hepatocytes while yielding reproducible results over multiple experiments. Nevertheless, even with HeparRG®, classical 2D culture methods are not sufficient to reproduce liver environment and physiology. In this study we propose to use our high-throughput encapsulation technology to generate organoids using these differentiated HepaRG® called HCLPearls® which can be used in a variety of ADME-TOX studies.

We generated liquid core microcapsules via coextrusion of suspended differentiated HepaRG® cells and alginate solution as the outer layer. After fragmentation into droplets, the alginate was cross-linked into a hydrogel. This shell protects the cells from shear stress while allowing efficient diffusion of oxygen, nutrients and small compounds and creating a micro-environment favoring the self-assembling of the cells into a spheroid within a few days.

We obtained organoids composed of 180 HepaRG® cells maintaining their viability and phenotypic integrity, without any appearance of necrotic core, and hepatic functions (CYP450 activity, transporter activity, urea production, albumin synthesis) for over a month, allowing their use for chronic studies. We then used these HCLPearls® to determine their suitability for several applications used in ADME-TOX. We showed CYP3A4 and CYP1A2 inducibility by reference inducers in the HCLPearls® model, demonstrating their usability for Drug-Drug-Interactions studies. We also demonstrated the suitability of our HCLPearls® for hepatotoxicity studies by conducting assays using reference compound such as Diclofenac and Acetaminophen.

ISCHEMIA-REPERFUSION CELLULAR MODELS TO IDENTIFY MITOCHONDRIA-TARGETED THERAPEUTIC SOLUTIONS

Léa Zennaro, Nelly Buron, Cécile Martel, Mathieu Porceddu, and Annie Borgne-Sanchez
MITOLOGICS SAS, Faculté de Santé, 8 rue du Général Sarrail, 94000 Créteil, France
aborgne.sanchez@mitologics.com

Mitochondria play a key role in intracellular energy production and controlling cell life and death. During ischemia, lack of nutrients and oxygen provokes metabolism inhibition and impairment of mitochondrial activity. During reperfusion, the sudden return of oxygen overwhelms mitochondrial capacity decreased by ischemia, leading to free radical production and cell death. As mitochondrial impairment constitutes the principal cause of tissue damage related to ischemia-reperfusion, we investigated the potential of mitochondrial transplantation as therapeutic approach to overcome mitochondrial default.
For this purpose, we set up two in vitro cellular models of kidney and brain ischemia-reperfusion, by inducing oxygen, glucose and glutamine deprivation in kidney LLC-PK1 and brain Neuro-2a cells. At reperfusion (return to normal culture conditions), the cells were directly treated with mitochondria, isolated from mouse liver (Porceddu et al., 2018; Buron et al., 2024). The ability of this strategy to rescue cell metabolism and survival after reperfusion was evaluated by assessing global oxygen consumption and cytotoxicity using our multiparametric assays.

The measures revealed that mitochondria addition significantly enhanced the respiration capacity in cells cultured in both normal and ischemia-reperfusion conditions. The mitochondrial recovery in pathological models was associated with an improvement of cell viability. These results demonstrated that our cellular models of kidney and brain ischemia-reperfusion can be used to identify new therapeutic solutions aiming to restore mitochondrial activity.

Buron N, Porceddu M, Loyant R, Martel C, Allard JA, Fromenty B, and Borgne-Sanchez A. Drug-induced impairment of mitochondrial fatty acid oxidation and steatosis: assessment of causal relationship with 45 pharmaceuticals, Toxicol. Sci., 2024. doi.org/10.1093/toxsci/kfae055.

Porceddu M, Buron N, Rustin P, Fromenty B, and Borgne-Sanchez A. In vitro assessment of mitochondrial toxicity to predict drug-induced liver injury. In book: Methods in Pharmacology and Toxicology – Drug-induced liver toxicity, 2018 Eds. M. Chen & Y. Will, Springer LLC, New York (NY, USA).

In vitro strategy for skin sensitization evaluation: physico-chemical properties and complex mixtures challenge

Rola BARCHAM, Christophe DINI – Oroxcell, Romainville France

Sensitization evaluation is an essential part of the safety assessment of substances. Several in vitro assays for the detection of sensitization were developed to permit the toxicological evaluation of these substances without the use of animals.

In parallel, the skin sensitization process was conceptualized as an Adverse Outcome Pathway (AOP) based on four key events (KE), and the existing assays can be linked to the evaluation of specific KE of the AOP through the defined Integrated Approaches to Testing and Assessment (IATAs). Among them, the first 3 KE can be evaluated in vitro by the evaluation of covalent binding to proteins (DPRA, ADRA, and kDPRA), the ARE-Nrf2 Luciferase Test (Keratinosens™, SENSIL-18, EPISENSA and LuSens), and the activation of dendritic cells (hCLAT, U-SENS™, GARD and IL-8 Luc assay).

However, the validated tests were developed for the evaluation of simple substances and not for substances difficult to test such as lipophilic substances requiring the use of organic solvents, or complex mixtures such as botanical extracts. Although possible, the testing was shown to be difficult mainly due to solubilization issues, to interference related to cytotoxic effects from the organic solvent or from a component of the mixture, or to the unavailability of the composition of the mixture.

We discuss here the limits of the tests described in the standard guidelines, together with the options developed at Oroxcell to address these issues, both by setting up innovative mixture characterization methods, by the development of new assays and by the adaptation of existing tests to substances difficult to test. Our integrative approach considerably extends the field of application of the assays towards complex substances and mixtures for toxicological assessment and efficacy against sensitization effect, and for the evaluation of photosensitization effect of these substances.

Integrated single-cell solutions for cell therapy profiling: a CAR-T case study

P. Barennes, H.P. Pham, M. Touati, V. Quiniou
Parean Biotechnologies

Cell therapies offer revolutionary potential but face challenges in manufacturing, monitoring, and efficacy characterisation. To overcome these challenges, single-cell technology emerges as a powerful tool, providing high-resolution analysis from quality control to immuno-monitoring. Our integrated workflow, comprising robust cytometry, efficient cell sorting, and single-cell analysis, helps in understanding cellular composition and functional attributes. Illustrated through a CAR-T case study, our approach offers insights for advancing cell therapy characterisation and personalised treatment strategies.

METAPROTEOMICS AS A KEY APPROACH TO IDENTIFY IMPACTS OF HIGH FAT (HIF) DIET ON THE GUT MICROBIOME.

METTON Isabelle*, COUTOS-THEVENOT Laure*, MONNEUSE Jean-Marc*, ROMAN François**, CEOLIN Laura**, VILLARD Vanessa**, SKORSKI Gilbert*
*Phylogene – France
**Amylgen – France

Introduction

Metagenomics remains limited to reach microbiota-host interactions and the understanding of mechanisms of actions. Modern mass spectrometry-based metaproteomics is powerful to assess and measure the host and microbiota proteins together and can address these questions, here on a HiF diet microbiome mouse model.

Materiel & Methods

Proteins from feces samples of HighFat diet and Standard Diet fed mice were extracted, then digested and analyzed by mass spectrometry. Proteins were identified and quantified. Through HolXplore pipeline, taxonomy was analyzed by peptide-based proteins classification and functional annotation by closest ortholog.

Results

This metaproteomics approach allowed the identification and relative quantification of 668 proteins in mice and 22373 microbials’. HolXplore analysis highlighted modifications of microbiota composition and a diminution of its diversity. Key biological functions as metabolism, signalization and host-symbiont interactions were modified by the diet.

Conclusion

Combination of taxonomic and functional results lay out an increase in inflammation processes, a higher risk of cancer and intestinal barrier disruption. Results also suggest alterations on the “gut-brain axis” with GABA-modulating bacteria imbalance and related function modifications. Finally, the results show profound metabolism modifications as well as mechanisms related to resistance to obesity and diabetes by increase of key bacteria species in HFD mice.

References:
1- Modern Metaproteomics: A Unique Tool to Characterize the Active Microbiome in Health and Diseases, and Pave the Road towards New Biomarkers—Example of Crohn’s Disease and Ulcerative Colitis Flare-Ups Henry A and all. 2022 Cells Apr; 11(8): 1340,
2- Five key aspects of metaproteomics as a tool to understand functional interactions in host-associated microbiomes.Salvato F and all. Plos Pathogens February 25, 2021
4- Metaproteomics—An Advantageous Option in Studies of Host-Microbiota Interaction.Karaduta O and all. Microorganisms. 2021 May; 9(5): 980.
3- Human gut microbiome:Function matters. Heintz-Buschart A and all. Trends in Microbiology. 2018, 26(7), P563-574, July 01, 2018

Innovative preclinic models to dissect molecular, cellular and tissular mechanisms in a physiological 3D-living tissue environment.

Dr. Amandine Roux

Research PIECES is a startup of Biotechnology labeled Deeptech and based on the campus of the University of Poitiers. The goals of the startup are to understand the physiology and the physiopathology of the Central Nervous System (CNS) through Research, Development & Treatment to fight against neurological diseases and to study the impact of the environment on the CNS. For that, we provide biological and innovative systems to dissect molecular, cellular and tissular mechanisms in a physiological 3D-living tissue environment.
90% of potential therapeutic molecules fail in the clinical trials phases due to the lack of robust and translatable preclinical models. So, we develop customizable, preclinical models with the advantages of in vivo and in vitro without the disadvantages.
Our models are physiological, no artificial (versus organoid/bioprinting), dynamic (versus in vivo) and integrated (versus in vitro), allowing to generate robust and translatable results, close to human physiology and thus, avoid failing in clinical trial phases. As an alternative to animal models, they also reduce drastically the number of animals used in R&D, following the EU rule of 2030.
They can be used for early drug discovery stages, tests of toxicity and in many therapeutic areas, as neurodegenerative diseases (Parkinson, Dementia with Lewy Bodies, etc.) or cancer. They can also permit to study the environment with the role of pesticides, or endocrine disruptors on the CNS. Our products/services are designed for all the researchers from Academia (CNRS, Inserm, etc.) to Pharmaceutical Industry (CRO, CDMO, etc.), and Army (as antidote to neurotoxins) and animal health (veterinary products). Research PIECES has the innovation to find the future therapeutic molecules of tomorrow to cure neurodegenerative diseases or cancer.

Screening&Fluidics, a breakthrough solution for the discovery of your biological agent based on droplet microfluidics.

The screening of biological agents has become an indispensable pillar of biotechnology routines, particularly for drug discovery and in vitro diagnostics from human or animal samples. Droplet microfluidics technology allows a scale analysis of unique biological objects through the encapsulation of these objects in pico-reactors formed by small droplets of water of about 40μm in diameter, in an insulating oil within microfluidic channels. These droplets are manipulated in microdevices built and controlled by methods borrowed from the microelectronics industry.

Screening&Fluidics is a service company providing ultra-high-throughput (uHTS) single-cell screening services using its GotaHit fluorescence-activated droplet sorting (FADS) platform. Our polyvalent team will assist you in the down scaling of your biological assay should it be simple or complex, phenotypic or functional. Then, we will sort tens of millions of cells based on this screening assay within a day. This platform can significantly shorten the discovery process of your antibodies or your biological agents. It can also be a powerful tool for identifying very rare events like circulating tumor cells. Should you have very specific screening needs, our experienced team will deploy its experience in machine design and tailor-made lab-on-a-chip systems to offer you tailored and high-performance solutions.

BIO-DIAMOND PROJECT: ADVANCING ALZHEIMER’S DISEASE MODELS FOR TARGET VALIDATION AND DRUG DISCOVERY

Ahmad ALLOUCHE2, Louise MINY1, Sonia KRIDI2, Jessica RONTARD1, Julie COLIN2, Benoît Guy, Christian MAISONNEUVE1, Nicolas VIOLLE2, Thibault HONEGGER1
Affiliations:
1 NETRI, 69007, Lyon, France
2 ETAP-Lab, 54500, Vandœuvre-lès-Nancy, France

Background: Increasing evidence implicates oligomeric forms of amyloid beta (AβO) and Tau (TauO) in the pathophysiology of Alzheimer’s disease (AD). The concurrent use of human-induced pluripotent stem cells (hiPSCs), microfluidic devices, and these oligomeric forms paves the way for a novel translational paradigm in drug screening. This approach should enable the testing of compounds directly on human cells, bridging the gap between animal models and human physiology.

Objectives: To present full characterization of the reproducibility of a microfluidic-based hiPSC culture, an essential tool toward developing physiologically relevant and up to the industry’s standards models of AD.

Methods: NETRI’s DuaLink Shift microfluidic system use for co-culture of hiPSC-derived glutamatergic and GABAergic neurons. This device features three compartments for precise isolation of soma, neurites, and synapses via microchannels. In collaboration with NETRI, we introduced AβO and TauO into a microfluidic co-culture of hiPSC-derived neurons. These oligomers, known for their neurotoxicity, were added at various concentrations and developmental stages. Our approach assesses their impact on different neuron types, replicating key aspects of Alzheimer’s pathology.

Results: A comprehensive characterization of the neuronal populations maintained for several weeks in microfluidic devices, using a range of analytical methods, including immunoassays, immunostaining, and electrophysiological activity assessments. These preliminary data highlight the impacts of the addition of peptides on neuronal activity. Conclusion: This represents a crucial step in the development of highly relevant, industry-standard models for AD. Such models can serve as indispensable resources for academic research teams and pharmaceutical industries alike, facilitating the elucidation of the pathological mechanisms of Alzheimer’s disease and the screening of new effective treatments.

Validation of a phage library-based panning strategy for the selection of specific anti-C5aR monoclonal antibodies

Human C5a receptor (hC5aR) is a G protein-coupled receptor for C5a, a fragment of complement component C5. Due to its function in modulating inflammation, hC5aR is one of the most studied targets for therapeutic applications. Nonetheless, hC5aR has been underused in the clinic so far since it is a transmembrane protein, which synthesis presents technical difficulties. Herein we describe the cell-free synthesis of hC5aR and its use for the implementation of a protein panning procedure aiming the generation and selection of specific anti-C5aR monoclonal antibodies, which could be used later in therapeutical applications.

Our RNA production platform and the associated tools facilitate the development of RNA-based vaccine

Célia Bosso-Lefèvre, Erica Cirri, Eric Mennesson, Marie Morin, Xavier Warnet, Dimitri Szymczak, Flavien Carpentier, Alexandra Foucher, Alzbeta Komarkova, Maxime Rochet, Armelle Vindrios, Laetitia Emond, Romain Goulay

Tebubio – 39 Rue de Houdan – Le Perray en Yvelines – France

mRNA vaccines have shown their full potential in the Covid-19 pandemic. The application of these technologies for the treatment of cancers represents significant hope, but clinical effectiveness remains to be demonstrated. For this purpose, researchers require high quality production of vaccine mRNA and accurate and cost-saving test tools that are adapted to oncology research. Since 2021, Tebubio has developed a miniscale RNA production platform for providing RNAs (from 100 µg to 1 mg) to researchers around the world. Through an ingenious design, our DNA matrix for mRNA is easily transferable for GMP production for clinical studies. This service is completed by offers on RNA delivery solutions using lipid nanoparticles (LNPs) and cellular tests with biomarker analysis.

We present a complete study on CAP1 capped linear RNA produced from our DNA templates. We assess the stability of two RNAs expressing GFP and the typical tumor antigen, p53, and their relative expression into antigen-presenting cells (APCs). Furthermore, we quantified the response of the APCs expressing p53 by using our biomarker multiplex analysis system. Finally, we present our formulation platform for the encapsulation of mRNAs inside Lipid Nanoparticles (LNP), showing both information regarding the ultrastructure of the LNPs, and RNAs expression in different cellular models. This new type of service and its future developments will constitute a new addition to our pipeline of RNA production and testing for preclinical studies.

Sponsor GOLD
15000 €

Sponsor SILVER
10000 €

Sponsor BRONZE
5000 €

EXPOSITION
à partir de 590€

Sponsor MAPSSI
à partir de 2000€

Profitez d’un dispositif déployé pour vous associer de manière qualitative aux AFSSI Connexions.

Positionnez-vous comme un acteur majeur du secteur.  Projetez-vous. Vous êtes au carrefour de l’innovation.

Sponsor MAPSSI

Affichez-vous sur l’édition 2017-1018 de la MAPSSI

Véritable mine d’informations – plébiscitée par tous les acteurs et opérateurs des sciences de la vie – la MAPSSI est un poster de 135cm par 115cm répertoriant les forces vives françaises des sociétés de services et d’innovation en Santé. La MAPSSI est éditée en partenariat avec Biotech Finances.

La MAPSSI sera à imprimée à 3000 exemplaires (soit 0,50€ par personne touchées)

Elle sera distribuée aux 400 participants des journées AFSSI et bénéficiera d’une mise en lumière particulière envers l’écoystème

3000ex

3000 exemplaires imprimés,
soit 0,50€ le contact ciblé

0,50€
MAPSSI 2015 en partenariat avec Biotech Finances
Demandez le modèle 2015
Contactez-nous
Commander

ICI UN VISUEL

Sponsor GOLD

Contactez-nous
Your Content Goes Here

Your Content Goes Here

Your Content Goes Here

Contactez-nous

Sponsor GOLD

Sponsor GOLD

BRONZE > 5000€ HT

  • Un emplacement privilégié d’environ 6m², avec 1 table et 4 chaises, intégrant un pass 2 jours
  • Votre logo et lien en page d’accueil du site Internet *
  • Votre logo et texte de présentation de votre société sur la page « Sponsor » du site Internet *
  • Sur les supports de communication suivants : votre logo sur la plaquette de commercialisation* et sur les opérations d’emailing (ex : Save the date, newsletter)*
  • Votre logo, film ou PowerPoint diffusé sur un écran plasma lors de l’événement*
  • 2 pass 2 jours offerts pour vous ou votre réseau (hors cabinets conseils extérieurs)
  • ½ page d’insertion publicitaire dans le programme des conférences remis sur place*

Titre

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