Alpha lipoic acid as a novel therapeutic approach to cystinuria

Abstract

Introduction: Cystinuria is a rare form of kidney stone disease inherited through mutations in the cystine transporter genes SLC3A1 and SLC7A9. Patients suffer from frequent and painful renal cystine calculus formation necessitating repeated radiation exposure, hospitalizations and surgical interventions. Available dietary and pharmacologic managements are burdensome to patients due to the sheer volume of pills and fluid that must be consumed and display limited efficacy. Areas Covered: The epidemiology, pathophysiology, and currently available options for dietary and pharmacological management including hyperhydration, modification of urinary pH, organosulfur drugs and crystal Inhibitors are reviewed. A novel drug in clinical trials, alpha lipoic acid (ALA), is presented and its hypothesized mechanism of action reviewed. Expert Opinion: A novel potential therapy, alpha lipoic acid, has been strikingly effective when used in a knockout mouse model. This compound is available over the counter as a food supplement, has been used in multiple human trials for other disease processes and has been shown to be safe and well tolerated. The promise of ALA is to reduce the burden of medications, stone events, surgical interventions, and financial concerns in cystinuric patients.

Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

“…Cystinuria, the recurrent formation of cystine-based kidney stones, with a high frequency of recurrence, often requiring repetitive surgical interventions to remove large stones [46], is caused by mutations in the SLC3A1 and/or SLC7A9 gene(s) [47]. Lipoic acid and derivatives can prevent or slow the development of cystine kidney stones [48].…”

What are the main challenges to the pharmacological management of cystinuria?

“…It has a lower side effect profile than tiopronin and D-penicillamine, but has not yet been evaluated in cystinuria [5]. Finally, α-lipoic acid (ALA) is a thiol-containing compound that is available as an over-the-counter supplement, shown to prevent cystine stone formation in animal models [14]. There is currently a Phase 2 clinical trial evaluating the efficacy of 1,200 mg of ALA three times a day in preventing cystine stone formation in cystinuria patients [15].…”