Ace Therapeutics has extensive expertise in processing induced pluripotent stem cell (iPSC) and iPS-derived neurons and providing timely, high-quality data. We are committed to providing valuable tools that shorten your time to develop treatments for psychiatric disorders, and we aim to support your preclinical drug development.

Introduction of iPSC-Derived Neural Cell Model Development for Schizophrenia

Because animal models are unable to replicate complex genetic diseases such as schizophrenia (SZ), patient-specific modeling tools are needed. Human iPSC overcomes the impracticality and poor accessibility of human brain cell types and offers the possibility to challenge and question the fate of neural cells before or during the onset of the disease in question. Considerable progress has been made in the neural differentiation of human pluripotent stem cells to mature neurons and brain-like organs. iPSC applications have been extended to model psychiatric disorders and generate patient-specific organoids. iPSC-derived neurons' ability to generalize basic neuronal functions (including excitation of action potentials and release of neurotransmitters) has led to the development of functional analysis of SZ-associated genetic variants.

Fig. 1 Alterations in iPSC-derived brain organoids modeling schizophrenia. (Räsänen N, et al., 2022)

iPSC-Derived Neural Cell Model Development Services

Ace Therapeutics provides services for schizophrenia research and anti-schizophrenia drug development based on human iPSC-derived neural models. Our researchers and scientists combine in-depth knowledge of cell engineering and RNA therapeutics to help accelerate your anti-psychotic drug development, including individualized drugs. Our preclinical services include patient iPSC reprogramming, cell line engineering, iPSC-neuronal differentiation, and ASO/ siRNA screening.

We offer iPSC and iPSC-derived neural cell models, including but not limited to

• Neural progenitor cells: Human neural progenitor cells (hNPC) form a useful cell system for high-throughput screening due to their homogeneity, low complexity and limited differentiation potential. In addition, we can reconstruct mutations in iPSCs and study the underlying molecular mechanisms using CRISPR/Cas9 and TALEN technologies. The mutated iPSCs were then differentiated into NPCs and neurons. NPC models can be used to study the association of mutations with abnormal brain development in schizophrenia.
• Glutamatergic neurons: Glutamatergic neurons can be used for the study of gene expression for neurotransmitter function, synaptogenesis and neuronal differentiation, and also for therapy development for drug-resistant SZ.
• Dopaminergic (DAergic) neurons: iPSC-derived DAergic neurons can be used to elucidate potential molecular mechanisms linking genetic variants in SZ patients to DAergic neuronal dysfunction.
• Aminobutyric neurons: Aminobutyric neurons are used to study SZ-associated GABA pathway signaling.
• Oligodendrocytes: Oligodendrocytes are used to study cellular stress, protein and ATP synthesis in SZ.

Ace Therapeutics has many years of research experience in the field of antipsychotic drug development. We provide physiologically relevant cellular models that can accelerate the discovery of psychiatric disease mechanisms. Genome editing in iPSC has been shown to be very effective in generating disease models for monogenic and complex genetic diseases. Using iPSC to model disease allows you to examine how specific types of cells are affected by the disease. We identify abnormal neuronal connections as assessed by dendritic arborization and synaptic density. We can identify genetic variants that are not identified by GWAS studies. If you are interested in our services, please feel free to make an inquiry.

References

1. Räsänen N, et al. The iPSC perspective on schizophrenia. Trends Neurosci. 2022, 45(1):8-26.
2. Abashkin DA, et al. Cellular Models in Schizophrenia Research. Int J Mol Sci. 2021, 22(16):8518.