# Advancements in Preclinical Models for NF2-Related Schwannomatosis Research

## TL;DR

This review discusses new preclinical models for NF2-related Schwannomatosis that help study neurological symptoms and improve treatment development.

## Contribution

The paper highlights novel mouse models and organotypic systems that replicate both tumor growth and associated neurological deficits in NF2-SWN.

## Key findings

- Mouse models now replicate tumor growth and neurological symptoms like hearing loss and ataxia.
- Organotypic culture systems and patient-derived xenografts have enhanced understanding of NF2-SWN biology.
- These models provide a foundation for developing effective therapies for NF2-SWN.

## Abstract

NF2-related Schwannomatosis (NF2-SWN) remains a disorder with limited effective therapeutic options. Progress in basic and translational research has historically been constrained by the lack of robust preclinical models that faithfully recapitulate the neurological deficits associated with vestibular schwannoma (VS), particularly hearing loss and ataxia. Recent advances, however, have led to the development of mouse models that reproduce these functional impairments, alongside the emergence of patient-derived xenografts and organotypic culture systems. In this review, we summarize currently available in vivo and ex vivo experimental models and discuss how these platforms have advanced our understanding of NF2-SWN biology and facilitated the identification of potential therapeutic strategies.

NF2-related Schwannomatosis (NF2-SWN) remains a disorder with few effective treatment options. Patients develop vestibular schwannomas (VSs) on both auditory nerves, which gradually impair hearing and often result in significant communication difficulties, social withdrawal, and higher rates of depression. Progress in understanding NF2-SWN biology and translating discoveries into therapies has been slowed by the absence of robust animal models that faithfully reproduce both tumor behavior and the associated neurological deficits. In this review, we summarized the development of animal models that not only reproduce tumor growth in the peripheral nerve microenvironment but also reproduce tumor-induced neurological symptoms, such as hearing loss and ataxia. We further highlight the currently available organotypic models for NF2-SWN. Together, these systems provide an essential foundation for advancing mechanistic studies and accelerating the development of effective therapies for this devastating disorder.