Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses

Title:Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses

Volume: 24 Issue: 16

Author(s): Sofia Carvalho, Luciana Moreira, Juliana Inês Santos, Paulo Gaspar, Mariana Gonçalves, Liliana Matos, Hugo David, Marisa Encarnação, Diogo Ribeiro, Ana Joana Duarte, Olga Amaral, Hugo Rocha, Luísa Diogo, Sara Ferreira, Constança Santos, Esmeralda Martins, Teresa Neuparth, Joana Soares, Marta Ribeiro, Brígida Ribeiro Pinho, Nuno Oliveira, Jorge Miguel Ascenção Oliveira, Maria João Prata, Miguel Santos, Sandra Alves and Maria Francisca Coutinho*

Affiliation:

• Research and Development Unit, Department of Human Genetics, INSA
• Center for the Study of Animal Science, CECA-ICETA, University of Porto
• Associate Laboratory for Animal and Veterinary Sciences, AL4 Animals

Abstract:

Introduction: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented two alternative and innovative protocols to mimic a particular sub-group of LSDs, the Mucopolysaccharidoses both in vitro and in vivo.

Methods: The first one relies on a non-invasive approach using dental pulp stem cells from deciduous teeth (SHEDs). SHEDs are multipotent neuronal precursors that can easily be collected. The second uses a state-of-the-art gene editing technology (CRISPR/Cas9) to generate zebrafish disease models.

Results: Even though this is an ongoing project, we have already established and characterized two MPS II and one MPS VI SHED cell models. These cells self-maintain through several passages and can give rise to a variety of cells including neurons. Furthermore, all MPS-associated sub-cellular phenotypes we have assessed so far are easily observable in these cells. Regarding our zebrafish models, we have successfully knocked down both naglu and hgsnat and the first results we got from the behavioral analysis are promising ones, as we can observe altered activity and sleep patterns in the genetically modified fish. For this particular approach we chose MPS III forms as our target disorders, since their neurological features (hyperactivity, seizures and motor impairment) and lifespan decrease would be easily recognizable in zebrafish.

Conclusion: Now that these methods are well-established in our lab, their potential is immense. On one hand, the newly developed models will be of ultimate value to understand the mechanisms underlying MPS sub-cellular pathology, which have to be further elucidated. On the other hand, they will constitute an optimal platform for drug testing in house. Also noteworthy, our models will be published as lab resources and made available for the whole LSD community.

Cite this article as:

Carvalho Sofia, Moreira Luciana, Santos Juliana Inês, Gaspar Paulo, Gonçalves Mariana, Matos Liliana, David Hugo, Encarnação Marisa, Ribeiro Diogo, Duarte Ana Joana, Amaral Olga, Rocha Hugo, Diogo Luísa, Ferreira Sara, Santos Constança, Martins Esmeralda, Neuparth Teresa, Soares Joana, Ribeiro Marta, Ribeiro Pinho Brígida, Oliveira Nuno, Ascenção Oliveira Jorge Miguel, Prata Maria João, Santos Miguel, Alves Sandra and Coutinho Maria Francisca*, Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses, Endocrine, Metabolic & Immune Disorders - Drug Targets 2024; 24 (16) . https://dx.doi.org/10.2174/0118715303277318231024055425

DOI https://dx.doi.org/10.2174/0118715303277318231024055425	Print ISSN 1871-5303
Publisher Name Bentham Science Publisher	Online ISSN 2212-3873