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Lysosomal storage diseases: current therapies and future alternatives

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Abstract

Lysosomal storage disorders (LSDs) are a group of monogenic diseases characterized by progressive accumulation of undegraded substrates into the lysosome, due to mutations in genes that encode for proteins involved in normal lysosomal function. In recent years, several approaches have been explored to find effective and successful therapies, including enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, hematopoietic stem cell transplantation, and gene therapy. In the case of gene therapy, genome editing technologies have opened new horizons to accelerate the development of novel treatment alternatives for LSD patients. In this review, we discuss the current therapies for this group of disorders and present a detailed description of major genome editing technologies, as well as the most recent advances in the treatment of LSDs. We will further highlight the challenges and current bioethical debates of genome editing.

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Funding

CJAD, AJEM, LHR, and JCC are supported by the Ministry of Science, Technology and Innovation, Colombia (Grant ID 120380763212—PPTA # 8352). CJAD and AJEM are supported by Pontificia Universidad Javeriana (PPTA # 8275). AFL received a doctoral scholarship from Pontificia Universidad Javeriana. OFS received a postdoctoral fellowship from the Ministry of Science, Technology and Innovation, Colombia (#811-2018).

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  1. Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Cra. 7 No. 43-82 Building 54, Room 305A, Bogotá D.C, 110231, Colombia

    Andrés Felipe Leal, Angela Johana Espejo-Mojica & Carlos Javier Alméciga-Díaz

  2. Neurobiochemistry and Systems Physiology, Biochemistry and Nutrition Department, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C., Colombia

    Oscar F. Sánchez

  3. Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá D.C., Colombia

    Carlos Manuel Ramírez & Luis Humberto Reyes

  4. Department of Biomedical Engineering, Universidad de los Andes, Bogotá D.C., Colombia

    Juan C. Cruz

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Leal, A.F., Espejo-Mojica, A.J., Sánchez, O.F. et al. Lysosomal storage diseases: current therapies and future alternatives. J Mol Med 98, 931–946 (2020). https://doi.org/10.1007/s00109-020-01935-6

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