Ksilink

Life & Brain GmbH long-standing member of Ksilink and partner in many exciting projects such as the one on microglia is attending the conference. An opportunity to talk about our developments with such cells an discuss potential drug discovery projects.

Join us for a two-day free event examining the role played by artificial intelligence and digital tools in understanding and supporting mental health. Hosted by the environMENTAL EU Project, Deutsches Zentrum für Psychische Gesundheit (DZPG) and EBRAINS, this event brings together experts within the field of mental health research, practice and policy. More information can be found on our website: https://lnkd.in/g8X-iRHP

Today is World Autism Awareness Day! 🧠 👩🔬 At Ksilink, it is one of our core missions to develop new therapeutic modalities to treat autism and particularly a rare form called Phelan McDermid Syndrome (PMDS). In line with the principle of the 3R, we developed a relevant human stem cell-derived neuronal model that recapitulates disease features with our collaborators at I-Stem (Establishment of heterozygous and homozygous SHANK3 knockout clonal pluripotent stem cells from the parental hESC line SA001 using CRISPR/Cas9 – ScienceDirect; Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models | bioRxiv). The deficit in SHANK3 protein (haploinsufficiency) which is a master scaffolding protein found in the postsynaptic density of excitatory synapses, is recognized as one of the major causes for different forms of autism including PMDS. Our current goal is to normalize the SHANK3 protein levels to physiological levels. If you want to know more about us and our journey to treat PMDS, please contact us: contact@ksilink.com #WorldAutismAwarenessDay #autism #ASD #PhelanMcDermidSyndrome #RareDisease #SHANK3 #stemcell #Ksilink #ISTEM #MedicalAdvancements #STEM #research #Neurodiversity https://lnkd.in/eC22giDZ

We, at #Ksilink, are proud to be part of the #environMENTAL WP 7 team exploring how we can create new ways of developing pharmacological interventions that support mental illness using authentic human stem-cell-derived neuronal models and AI-assisted cellular profiling technologies.

Great event in Paris bringing together experts from academia and industry to foster RNA based medicine. An excellent opportunity for #Ksilink to illustrate our #biotherapy approach, based on the discovery of novel targets and antisense oligo nucleotides #ASO on most authentic patient-based models. Thanks a lot #HYBRIDAY team!

🎉 Exciting news! We’ve just published a new paper on the impact of Endocrine Disrupting Chemicals (EDCs) on human stem cell-derived neurons. The project was spearheaded by Andrea Di Credico (Università degli Studi "G. d'Annunzio" Chieti - Pescara) and Amélie Weiss (Ksilink). Our research focused on bisphenols (BPs) and perfluoroalkyls (PFs), chemicals commonly found in plastics and household products. We analyzed their effects on human stem cell-derived midbrain dopaminergic neurons (mDANs), a key cell type affected in Parkinson's disease (PD). We used machine learning (ML) models to classify EDC-treated versus control mDANs based on 126 different phenotypic features. The results? EDC-treated mDANs were identified with high accuracies (0.88–0.96), showing that EDCs induce significant changes in these cells. Most notably, we found that EDC exposure led to an increase in alpha-synuclein (αSyn) and tyrosine hydroxylase (TH) staining intensity within the neurons, and a decrease in microtubule-associated protein 2 (MAP2) neurite length and branching. Partially, these changes are also characteristic of PD, suggesting that EDCs may play a role in the disease’s development. This study underscores the power of ML-supported high-content imaging in identifying subtle but significant phenotypic changes. We’re excited about the potential of this approach for further pathological characterization in the future. 🧪🔬🧠 #ParkinsonsResearch #EndocrineDisruptors #MachineLearning https://lnkd.in/errJenGJ

New exciting science from Ksilink highlighting our expertise in neurodevelopmental disorders, stem cell biology and screening. We performed a compound screen & modulated Phelan-McDermid syndrome (PMDS) phenotypes in stem cell-derived cortical neurons. https://lnkd.in/gYPFiNHr This project was only possible by bringing together stem cell differentiation, laboratory automation, compound screening, imaging, CRISPR, electrophysiology, and much more. A great thank you to my present and former Ksilink colleagues Amandine THIBAUDEAU, Karen Schmitt, PhD, David Hoffmann, Loïc Cousin, Amelie Weiss, Aurore VUIDEL, Christina Jacob, Peter Sommer, PhD and our collaborators at I-Stem for making this happening. PMDS, often associated with autism spectrum disorder (ASD), arises from mutations impacting the SHANK3 gene on chromosome 22q13. In our study, we examined 12 different PMDS patient and CRISPR-engineered stem cell-derived neuronal models and controls. Our goal was to understand how SHANK3 deficiency affects neuronal development and function. Our findings revealed that reduced expression of SHANK3 leads to neuronal hyperdifferentiation, increased synapse formation, and decreased neuronal activity. We performed automated imaging-based screening of 7,120 target-annotated small molecules. This led us to identify three compounds that rescued SHANK3-dependent neuronal hyperdifferentiation. Notably, one compound, Benproperine, rescued the decreased colocalization of Actin Related Protein 2/3 Complex Subunit 2 (ARPC2) with ß-actin and rescued increased synapse formation in SHANK3 deficient neurons when administered early during differentiation. However, neuronal activity was only mildly affected by Benproperine, highlighting its effects as a neurodevelopmental modulator rather than a modulator of mature neuronal function. This research underscores the potential of small molecular compounds that reverse developmental phenotypes in human neuronal PMDS models. It also emphasizes the importance of understanding both developmental and synaptic neurobiology in designing successful PMDS treatment strategies.