Gene therapy for lysosomal storage diseases and peroxisomal diseases


Gene therapies for lysosomal storage diseases (LSD) and peroxisomal diseases (PD) are rapidly advancing. Most LSDs and PDs are characterized by brain involvement, prompting the development of therapies targeting the brain. There are two types of gene therapy for brain involvement in LSD and PD, i.e., the direct transfer of a therapeutic gene into brain cells and hematopoietic stem cell-targeted gene therapy. The rationale for the latter approach is that brain microglia are derived from hematopoietic cells. Thus, gene-corrected hematopoietic cells migrate into the brain and differentiate into microglial cells. These gene-corrected microglial cells correct the metabolic defects associated with LSD and reduce inflammation in PD and LSD, leading to a clinical benefit. Gene editing technology has recently been applied in this area and a trial focused on LSD is currently ongoing. Although these approaches are still under investigation, very encouraging results have been obtained. This review provides an overview of recently developed gene therapies for various LSDs and PDs, including the results of clinical trials, with an emphasis on the benefits of this approach for these diseases.

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Correspondence to Toya Ohashi.

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Conflict of interest

T. Ohashi have active research support from Sanofi Genzyme Corporation, Sumitomo Dainippon Pharma and Avrobio, Inc. . These activities have been fully disclosed and are managed under Memorandum of Understanding with the Conflict of Interest Resolution Board of the Jikei University School of Medicine.

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Ohashi, T. Gene therapy for lysosomal storage diseases and peroxisomal diseases. J Hum Genet 64, 139–143 (2019).

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