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Evaluation of ranirestat for the treatment of diabetic neuropathy
1University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Department of Pathology and Immunology , 4401 Penn Avenue, Pittsburgh, PA 15224 , USA +1 412 692 8127 (voice) ; +1 412 692 7515 ; ngiann1@pitt.edu.
Introduction:
Pharmacologic maintenance of normoglycemia in diabetes cannot prevent the eventual complications mainly due to protein glycation-induced cell death, dysregulated antioxidant defense and signal transduction in affected tissues. The rate-limiting enzyme of this process, aldose reductase, is therefore a pharmacologic target. To date, nine inhibitors of this enzyme have been developed. Ranirestat has completed two Phase III clinical trials. The objective of this evaluation is to summarize and provide expert opinion on the status of ranirestat with an emphasis on its pharmacokinetics in the context of its potential effects to prevent/treat diabetic complications.
Areas Covered:
A qualitative systematic literature search of PubMed through November 2013 using MeSH terms - aldose reductase inhibitors, diabetic neuropathy, AS-3201, ranirestat, diabetic complications and pharmacokinetics/pharmacodynamics - identified relevant publications limited to human and rodent (mouse and rat) and English-language studies.
Expert Opinion:
Ranirestat is a well-tolerated front-line inhibitor. It reproducibly exhibits some degree of measurable objective beneficial outcomes in diabetic neuropathy. It is the furthest advanced in clinical trials with some depth of supporting preclinical data. Trials in subjects with newly diagnosed neuropathy along with the identification of objective biomarkers/measurements of efficacy will be critical in identifying the real value and effect of ranirestat.
Insights
Ranirestat, an aldose reductase inhibitor, shows promise in treating diabetic complications. This well-tolerated drug demonstrates objective benefits in diabetic neuropathy, with ongoing trials to confirm its full potential.
Area of Science:
- Pharmacology
- Diabetology
- Biochemistry
Background:
- Diabetic complications stem from protein glycation, impacting cell function.
- Aldose reductase is a key enzyme in this glycation process.
- Developing aldose reductase inhibitors is crucial for managing diabetes complications.
Purpose of the Study:
- To evaluate the status of ranirestat, an aldose reductase inhibitor.
- To analyze ranirestat's pharmacokinetics and potential in preventing/treating diabetic complications.
- To provide an expert opinion on ranirestat's clinical advancement.
Main Methods:
- Systematic literature search of PubMed up to November 2013.
- Included human and rodent studies on aldose reductase inhibitors and diabetic complications.
- Focused on keywords: aldose reductase inhibitors, diabetic neuropathy, ranirestat, and pharmacokinetics/pharmacodynamics.
Main Results:
- Ranirestat is a well-tolerated, front-line aldose reductase inhibitor.
- Demonstrates reproducible, measurable benefits in diabetic neuropathy.
- Advanced furthest in clinical trials with supporting preclinical data.
Conclusions:
- Ranirestat shows objective beneficial outcomes in diabetic neuropathy.
- Further trials in early-stage neuropathy and biomarker identification are critical.
- Confirming efficacy will define ranirestat's true value in managing diabetic complications.
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