Probiotic therapy for primary hyperoxaluria
PH is a rare and life-threatening disease associated with a dysfunction in glyoxylate metabolism. It has a prevalence of 1-3 per million and it usually presents at birth with high levels of oxalate that damage the kidney and cause end-stage renal failure in over 50 % of the cases. Currently, there is no approved pharmaceutical therapy for this devastating disease. Over the years, the knowledge about the human microbiota and its role in health and disease has led to an interest in the use of naturally occurring bacteria from the human gut as pharmaceutical drugs. Scientists of the EU-funded ELIMOX (Biopharmaceutical therapy for treatment of primary hyperoxaluria) project proposed a new approach that utilises bacteria to breakdown excessive oxalate in the gut, inducing an alternative pathway for the oxalate, thereby protecting the kidneys from failure. Towards this goal, they developed a new drug from Oxalobacter formigenes, an anaerobic bacterium whose only carbon source is oxalate. Considerable effort went towards understanding the characteristics of O. formigenes to optimise the manufacturing process of the bacteria for pharmaceutical use. Scientists developed specialised analytical methodology for mapping and quantifying the presence of microbes in the human gut, and for monitoring the clinical effects after treatment. The drug was produced in the form of enteric-coated gelatin capsules containing lyophilised viable O. formigenes bacteria. Two clinical studies were conducted on patients with normal kidney function and on patients who were on dialysis. Despite patient heterogeneity, a correlation was observed between renal function and the plasma oxalate concentration. There were no safety issues and treatment response was related to individual stage of kidney deterioration. Interestingly, there was an indication that oxalate deposits were dissolving in treated patients. Encouraging results were also obtained regarding heart function and the total and free plasma oxalate levels of patients on dialysis. Overall, the results of the clinical studies led to patent application for the probiotic drug. The application of the ELIMOX intervention extends beyond PH and could be used to treat other metabolic or malabsorption disorders.
Keywords
Probiotic, primary hyperoxaluria, oxalate, ELIMOX, Oxalobacter formigenes
