News

In the forefront of developing new human cell models for neurodegenerative diseases

- first neuronal in vitro cell model for frontotemporal dementia using patient-derived iPS cells

In a recent study, published by Zhang et al., the first-ever induced pluripotent stem cell (iPSC)-based neuronal model from patients with frontotemporal dementia 3 (FTD3) is described. This disease has previously only been studied at the molecular level in mouse and Drosophila animal models as well as in patient-derived fibroblasts. Bioneer has played an integral role in the study, including the establishment of isogenic gene-corrected iPS cell lines and in performing many of the assays described in the publication.

Neurons generated in vitro from FTD3 patient-derived iPSCs carrying a point mutation in the CHMP2B gene were compared with isogenic controls generated with the CRISPR/Cas9 system as well as neurons from a healthy control. The FTD3-neurons showed many phenotypical traits that has previously been demonstrated in patients or primary cell models, such as aberrant endosomes, abnormal mitochondria leading to reduced mitochondrial function and increased oxidative stress, reduced neurite length and soma size, as well as up- or downregulation of several neurodegenerative disease-associated genes.

“The unique model, based on the differentiation of patient specific pluripotent stem cells, opens up for researchers active in the neurodegenerative disease field to further investigate the biologic pathogenesis, come up with new therapeutic targets, and/or test current drug candidates for their ability to rescue the diseased phenotype”, says Bjørn Holst, R&D Manager for Disease Models at Bioneer A/S.


The exciting work presented in the publication is a result of a cross-national effort with the majority of the work carried out at the University of Copenhagen, H. Lundbeck A/S and Bioneer A/S.

“This study highlights the expertise in generating and validating in vitro disease models at Bioneer. This is an important milestone in our strategy to be a preferred partner for industry and research institutes in the area of disease modelling and downstream drug discovery processes”, says Christian Clausen, R&D Director at Bioneer A/S.

Bioneer A/S is a research-based service provider, offering advanced R&D platforms, such as a gene editing core facility. Through the last decade, Bioneer has been working continuously with iPSCs and combined with the advanced knowledge in genetic engineering, Bioneer has been involved in many national and international R&D projects together with academia, biotech and big pharma industry. The accumulated expertise has led to the establishment of several different neurodegenerative disease models within Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia.


If you are interested in learning more about Bioneer’s capabilities within the field, please feel free to contact either Christian Clausen (ccl@bioneer.dk) or Bjørn Holst (bho@bioneer.dk) at +45 45 16 04 44.


Link to publication here.