The landscape of pathophysiology guided therapeutic strategies for gout treatment

ABSTRACT

Introduction

Gout is a common autoinflammatory disease caused by hyperuricemia with acute and/or chronic inflammation as well as tissue damage. Currently, urate-lowering therapy (ULT) and anti-inflammatory therapy are used as first-line strategies for gout treatment. However, traditional drugs for gout treatment exhibit some unexpected side effects and are not suitable for certain patients due to their comorbidity with other chronic disease.

Areas covered

In this review, we described the pathophysiology of hyperuricemia and monosodium urate (MSU) crystal induced inflammatory response during gout development in depth and comprehensively summarized the advances in the investigation of promising ULT drugs as well as anti-inflammatory drugs that might be safer and more effective for gout treatment.

Expert opinion

New drugs that are developed based on these molecular mechanisms exhibited great efficacy on reduction of disease burden both in vitro and in vivo, implying their potential for clinical application. Moreover, hyperthermia also showed regulation effect on MSU crystals formation and the signaling pathways involved in inflammation.

KEYWORDS:

• Gout
• inflammation
• NLRP3 inflammasome
• pathogenesis
• therapy

Article highlights

• Current urate-lowering drugs as well as anti-inflammatory drugs are not suitable for certain patients with contraindication due to their side effects.

• Uricosurics exhibit nephroprotective and cardioprotective properties in combination with XOIs.

• NLRP3 inflammasome is a promising therapeutic target for anti-inflammatory therapy of gout patients.

• Regulating cell death such as NETosis and apoptosis could effectively inhibit inflammation induced by MSU crystals.

• Hyperthermia has the potential for gout treatment through regulation MSU crystals formation and the signaling pathways involved in inflammation.

Declaration of interest

The authors have 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 work was supported by grants from the National Natural Science Foundation of China (No. 82200160); Open Project of Zhejiang Provincial Key Laboratory of Drug Prevention and Control Technology Research (2020014).