Advances and challenges in modeling inherited peripheral neuropathies using iPSCs

Abstract

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids. Inherited peripheral neuropathies are diseases that cause damage to the motor and sensory nervous system. Despite progress in understanding these diseases, effective treatments are still hard to find. This study looks at using induced pluripotent stem cells (iPSCs - cells that can turn into any type of cell in the body) to mimic the disease and find possible drug targets. The scientists used iPSCs to create different nerve cells and Schwann cells (cells that support nerve function). They studied these cells to see how the disease affects them. The study found that models made from iPSCs can accurately copy key aspects of the disease, providing valuable insights that add to findings from animal models. This research could lead to new treatments for inherited peripheral neuropathies. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.