Promising therapeutic targets for the treatment of urine storage dysfunction: what’s the status?

ABSTRACT

Introduction

Opinions differ on what drugs have both a rationale and a development potential for the treatment of bladder storage dysfunction.

Areas covered

In the present review, the focus is given to small molecule blockers of TRP channels (TRPV1, TRPV4, TRPA1, and TRPM8), P2 × 3receptor antagonists, drugs against oxidative stress, antifibrosis agents, cyclic nucleotide – dependent pathways, and MaxiK±channel – gene therapy.

Expert opinion

TRPV1 channel blockers produce hypothermia which seems to be a problem even with the most efficacious second-generation TRPV1 antagonists. This has so far precluded their application to urine storage disorders. Other TRP channel blockers with promising rationale have yet to be tested on the human lower urinary tract. The P2 × 3receptor antagonist, eliapixant, was tested in a randomized controlled clinical trial, was well tolerated but did not meet clinical efficacy endpoints. Antifibrosis agent still await application to the human lower urinary tract. New drug principles for oxidative stress, purine nucleoside phosphorylase inhibition, and NOX inhibition are still at an experimental stage, and so are soluble guanylate cyclase stimulators. Gene therapy with MaxiK±channels is still an interesting approach but no new trials seem to be in pipeline.

KEYWORDS:

• Lower urinary tract symptoms
• overactive bladder syndrome
• detrusor overactivity
• TRP channels
• P2X3 receptors
• antifibrosis
• oxidative stress
• soluble guanylate cyclase stimulators
• MaxiK±channels

Article highlights

• TRV channel blockers have a good treatment rationale but a proof of concept for use in the treatment of LUT disorders is still lacking.

• Current P2×3channel blockers do not seem to be a competitive treatment alternative.

• New possible treatments of oxidative stress – inhibitors of purine nucleoside phosphorylase and NOX – are still at an experimental stage.

• Antifibrosis agents are available, and offer an interesting opportunity, but proof of concept studies are lacking.

• sGC stimulators have a translational potential – proof of concept is lacking

• Gene therapy with MaxiK+ channels – promising initial data but no new information in sight.

Declaration of interest

The author has no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.