New Fast, Reliable Model Tests Patient Response to Novel Treatments

New Fast, Reliable Model Tests Patient Response to Novel Treatments 150 150 Madison Storm

It’s well-known that treatments work for some patients and don’t for others, and this can be a real challenge when it comes to rare neurogenerative disorders. Dr. Kathrin Meyer and her lab established a faster, reliable in vitro model to investigate why.

Recent research from the Meyer lab with the Center for Gene Therapy at the Abigail Wexner Research Institute (AWRI) is making waves in understanding treatment outcomes for neurodegenerative diseases, with a focus on spinal muscular atrophy (SMA) and IGHMBP2-related disorders, specifically those caused by IGHMBP2 gene mutations, including SMARD1 and CMT2S.  

This study established a novel in vitro model to generate induced neurons, which will make disease impact and progression in patients easier to understand and can also test treatment responses to available gene therapies. 

“One shortcoming in research is the variability of patients; what treatment works for one person may not work as well for another,” Dr. Meyer says. 

To better understand why that is, the study used skin fibroblasts (a type of cell), which were converted into induced neurons, from patient cell lines with SMA, SMARD1 and/or CMT2S. These induced neurons were then treated with current clinical gene therapies, including Zolgensma for SMA and AAV9.IGHMBP2 for those with IGHMBP2-related disorders.  

While treatment response varied among cell lines, researchers also found irregularities in the form of the converted induced neuron samples. Once identified, these irregularities could then be corrected through available gene therapy treatments. This provides the opportunity for a deeper investigation and understanding of disease variations of individual patients based on genetic classification/phenotype and response to treatment.  

Additionally, the research offers potential improvements in the evaluation and characterization of variants of uncertain significance (VUS), which is crucial to understanding mutation significance and patient health impact as a result. These improvements are made possible through the preservation of natural epigenetic markers within patient cell lines, as researchers can observe cells that are more reflective of the disorder’s natural biological state. 

By using a direct conversion method to transform skin cells into induced neurons, the in vitro model preserves more epigenetic markers. Preservation of epigenetic markers is crucial in the study of disease mutations because they may be identified as disease modifiers.  

The direct conversion method allowed for a new, faster way of identifying disease modifiers and characterizing variants in patient cell lines, which can help clinicians better understand individual patient responses to available gene therapies. Simply put, this research has helped make the unknown become known faster. 

Findings indicate the induced neurons used in this study were responsive to current clinical gene therapy treatments and the established in vitro model can be used as a fast, reliable way of testing new treatments, evaluating disease modifiers and characterizing VUS, supporting Nationwide Children’s Hospital’s overall goal of improved patient outcomes. 

But their work doesn’t end here. The Meyer lab is now working on further developing and standardizing the system to establish standard operating procedures, as well as even faster turnaround times. Additionally, the Meyer lab is expanding their work with SMA/SMARD1 patient cell lines to study additional cell types and test additional therapeutics. 

“We hope to integrate this methodology in upcoming clinical trials,” says Dr. Meyer, and those initial conversations are already underway. “There is still some way to go, but I think in the future, methods like these will hopefully help clinical trial interpretation and therapy selection.” 

Studies like this are the focus of Dr. Meyer’s lab, which emphasizes better understanding the differences in disease severity and course among patients with neurodegenerative diseases. And there’s always more to discover, according to Dr. Meyer. 

“We are also in the process of using the same methodology on other diseases with the aim to hopefully assist future clinical trials in patient stratification and to identify potential common disease pathways that could be targeted with similar therapeutic approaches.” 



Sierra-Delgado, J. A., Sinha-Ray, S., Kaleem, A., Ganjibakhsh, M., Parvate, M., Powers, S., Zhang, X., Likhite, S., & Meyer, K. (2023). In Vitro Modeling as a Tool for Testing Therapeutics for Spinal Muscular Atrophy and IGHMBP2-Related Disorders. Biology12(6), 867.

About the author

Senior Strategist, Research Communications | Website

Madison Storm is the Senior Strategist of Research Communications at Nationwide Children's Hospital. She earned her bachelor's in multimedia journalism from Virginia Tech in 2021 and went on to achieve her master's in health communication from Johns Hopkins University in 2023. Her passion for transforming the complex to clear is supported by various experiences writing for consumer audiences.