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Gene Therapy and Overactive Bladder

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Abstract

Purpose of Review

Within the last decade, a number of gene therapies have been developed as a treatment option for monogenic diseases. Overactive bladder is a multifactorial syndrome with likely many underlying causes and regulatory components. The goal of this paper is to review current gene therapy in and outside of the genitourinary system, review the pathophysiology and genetics of OAB, and discuss recent advances in application of this technology for OAB treatment.

Recent Findings

Various genes have been found to be upregulated in OAB patients including receptors involved in purinergic signaling, gap junctions between detrusor smooth muscle cells, proteins involved in detrusor myocyte cytoskeletal dynamics, cholinergic receptors, and some types of membrane channels. Fewer genes are downregulated but include receptors in purinergic signaling and a channel critical for detrusor smooth muscle cell relaxation. Results of a recent phase 2 trial exploiting a gene coding for a portion of a potassium channel suggest that gene therapy may have emerging relevance in OAB therapy.

Summary

OAB is a syndrome, and the pathophysiology is incompletely understood but likely is due to a combination of altered afferent signaling at the level of the bladder modified by a constant hyper- or hypo-excitability of the detrusor myocyte. Understanding the complex pathways underlying OAB as well as the related genetic components of the normal and abnormal bladder may provide novel therapeutic options for this widespread condition.

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  1. Department of Urology, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB 620, Charleston, SC, 29425, USA

    Stephen Patrick & Eric Rovner

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S.P. and E.R. equally contributed to the manuscript.

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Correspondence to Eric Rovner.

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E.R. was the central urodynamics reader and consultant on behalf of Ion Innovations and Urovant in the study of URO-902

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Patrick, S., Rovner, E. Gene Therapy and Overactive Bladder. Curr Bladder Dysfunct Rep 19, 37–43 (2024). https://doi.org/10.1007/s11884-023-00733-3

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