# Induced Pluripotent Stem Cells for the Treatment of Lysosomal Storage Disorders

## TL;DR

This paper reviews how induced pluripotent stem cells (iPSCs) could be used to model and treat lysosomal storage disorders, which are rare genetic diseases affecting metabolism and the nervous system.

## Contribution

The paper highlights iPSCs as a novel platform for disease modeling and regenerative therapy in neuropathic lysosomal storage disorders.

## Key findings

- iPSCs can replicate LSD neuropathology in vitro for research purposes.
- iPSCs show potential for in vivo regeneration by replacing damaged cells in LSD patients.
- Current therapies fail to reverse neurodegeneration, but iPSCs offer a promising alternative.

## Abstract

Lysosomal disorders (LSDs) are a group of rare metabolic disorders, with an overall incidence of 1:4800 to 1:8000 live births. LSDs are primarily caused by dysfunctional lysosomal enzymes, which typically lead to the progressive accumulation of substrates within cellular lysosomes. As a result, patients experience a wide array of somatic symptoms such as visceromegaly, cardiopulmonary abnormalities, and respiratory and urinary infections. Additionally, over two‐thirds of LSD subtypes have a neurological component, and without treatment, patients experience neurodegeneration, cognitive decline, and life expectancies spanning infancy to adulthood. At present, there is no therapy that rescues the degenerative neuropathology of LSDs, and current developments, such as brain‐targeted enzyme replacement therapy, hematopoietic stem cell transplantation, and even gene therapy, can only prevent further neurodegeneration. However, recent advancements involving induced pluripotent stem cells (iPSCs) have demonstrated that stem cells may harbor the potential to both recapitulate the phenotype of neuropathic LSDs in vitro, as well as serve as a vector for regeneration in vivo, by replacing cells and neurons damaged by disease progression. This review reports the current state of iPSC technology in LSD research, and the pathway by which iPSCs are translated from disease modeling to serving as a regenerative therapeutic for neuropathic LSDs in the clinic.