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Induced Pluripotent Stem Cells in Huntington’s Disease: Disease Modeling and the Potential for Cell-Based Therapy

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Abstract

Huntington’s disease (HD) is an incurable neurodegenerative disorder that is characterized by motor dysfunction, cognitive impairment, and behavioral abnormalities. It is an autosomal dominant disorder caused by a CAG repeat expansion in the huntingtin gene, resulting in progressive neuronal loss predominately in the striatum and cortex. Despite the discovery of the causative gene in 1993, the exact mechanisms underlying HD pathogenesis have yet to be elucidated. Treatments that slow or halt the disease process are currently unavailable. Recent advances in induced pluripotent stem cell (iPSC) technologies have transformed our ability to study disease in human neural cells. Here, we firstly review the progress made to model HD in vitro using patient-derived iPSCs, which reveal unique insights into illuminating molecular mechanisms and provide a novel human cell-based platform for drug discovery. We then highlight the promises and challenges for pluripotent stem cells that might be used as a therapeutic source for cell replacement therapy of the lost neurons in HD brains.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China to T.W. (31171211 and 81471305), N.X. (81200983), and J.S.H. (81301082); a grant from China Medical Foundation to N.X. (2012B09); and a grant from Hubei Molecular Imaging Key Laboratory to N.X. (0203201343).

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    Authors and Affiliations

    1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

      Ling Liu, Jin-Sha Huang, Chao Han, Guo-Xin Zhang, Xiao-Yun Xu, Yan Shen, Jie Li, Hai-Yang Jiang, Nian Xiong & Tao Wang

    2. Department of Psychiatry, Harvard Medical School; Division of Alcohol and Drug Abuse, and Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, USA

      Zhi-Cheng Lin

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    1. Ling Liu
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    Correspondence to Tao Wang.

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    Ling Liu and Jin-Sha Huang contributed equally to this work.

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    Liu, L., Huang, JS., Han, C. et al. Induced Pluripotent Stem Cells in Huntington’s Disease: Disease Modeling and the Potential for Cell-Based Therapy. Mol Neurobiol 53, 6698–6708 (2016). https://doi.org/10.1007/s12035-015-9601-8

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