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Correcting Neuronal Hyperdifferentiation in Phelan-McDermid Syndrome​

At Ksilink, we are at the forefront of research into Phelan-McDermid syndrome (PMDS), a condition linked to a deficiency of the SHANK3 protein, a key component of the brain’s synapses. PMDS is associated with autism spectrum disorder (ASD).​

Our team has examined a variety of PMDS patient and CRISPR-engineered stem cell-derived neuronal models. We found that reduced SHANK3 expression results in neuronal hyperdifferentiation, increased synapse formation, and decreased neuronal activity.​

But our research doesn’t stop at understanding the problem. We have also screened thousands of small molecules in human SHANK3-deficient neurons to find potential treatments.

We identified multiple compounds that can reverse SHANK3-dependent neuronal hyperdifferentiation and have identified a possible mode of action.​

We believe that using small molecular and biologics screening approaches in human PMDS models will uncover cellular pathways that can enhance cortical development and synaptic homeostasis. This could significantly boost the chances of developing successful PMDS treatments.​

Mapping and Modulating Human Microglial Diversity

At Ksilink, we are exploring the diversity of microglia, the brain’s immune cells, playing a crucial role in maintaining brain homeostasis under a variety of conditions. However, in the face of certain central nervous system diseases, microglia can become overly active or passive, leading to a failure in their essential tasks.​

Our mission is to map the diversity of human stem cell-derived microglia. To achieve this, we are utilizing a scalable microscopy approach coupled with an artificial intelligence-driven phenotype classification. This innovative combination allows us to explore the vast heterogeneity of microglia in unprecedented detail.​

But our exploration does not stop there. We are also employing drug screening techniques to identify chemical modulators capable of inducing specific microglial populations. This approach opens up new possibilities to predict complex functional assay outcomes using rapidly deployable imaging techniques and for targeted interventions in microglial biology​