Emerging therapies for overactive bladder: preclinical, phase I and phase II studies

ABSTRACT

Introduction

Overactive bladder syndrome is a common chronic condition with a significant impact on quality of life and economic burden. Persistence with pharmacologic therapy has been limited by efficacy and side effects. A greater understanding of the pathophysiology of overactive bladder has led to the initial evaluation of several drugs affecting ion channels, the autonomic nervous system, and enzymes which may provide useful alternatives for the management of overactive bladder.

Areas covered

A comprehensive review was performed using PubMed and Cochrane databases as well as reviewing clinical trials in the United States. The current standard of care for overactive bladder will be discussed, but this paper focuses on investigational drugs currently in preclinical studies and phase I and II clinical trials.

Expert Opinion

Current therapies for overactive bladder have limitations in efficacy and side effects. A greater understanding of the pathophysiology of overactive bladder has identified the role(s) of other pathways in the overactive bladder syndrome. Targeting alternative pathways including ion channels and enzymes may provide alternative therapies of overactive bladder and a more tailored approach to the management of overactive bladder.

KEYWORDS:

• Anticholinergic
• beta-agonist
• enzyme
• gene therapy
• overactive bladder
• pharmacologic therapy

Article highlights

• Overactive bladder syndrome (OAB) is very common and associated with a significant impact on quality of life and economic burden.

• Currently, the mainstay of pharmacologic therapy is anticholinergic agents and beta-3 adrenoceptor agonists.

• Opportunities exist to optimize the efficacy and tolerability of pharmacologic therapy for OAB.

• Preclinical studies have been performed evaluating the impact of ion channel agonists, ion channel antagonists, phosphodiesterase (PDE) inhibitors, rho-kinase inhibitors, and other therapies.

• Phase I and II clinical trials have assessed the safety and efficacy of anticholinergic agents, beta 3-adrenoceptor agonists, PDE-5 inhibitors, potassium channel openers, and gene therapy.

• Future studies are needed to determine if these therapies will prove effective as monotherapies and/or serve a role in combination therapy.

Declaration of interest

P Ellsworth has been affiliated with Astelllas Pharma as a Clinical Trial Investigator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.