ELIMOX

Biopharmaceutical therapy for treatment of Primary Hyperoxaluria

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 Obiettivo del progetto (Objective)

'Interest in the use of naturally occurring human gut bacteria as pharmaceutical drugs has increased as knowledge about the human microbiota and its role in health and disease has advanced. The ELIMOX project proposes to develop a new drug from Oxalobacter formigenes, an anaerobic bacterium whose only carbon source is oxalate, for the treatment of primary hyperoxaluria (PH). PH is a rare and life-threatening disease, present at birth, characterised by high endogenous levels of oxalate that damage the kidney and cause renal failure. Enteric elimination of oxalate via the gut provide an alternative elimination pathway for the oxalate and treatment with pharmacological doses of O. formigenes would facilitate such enteric elimination. The treatment employs a new approach whereby bacterial breakdown of excessive oxalate occurs in the gut, inducing an alternative pathway for the oxalate, thereby protecting the kidneys from failure. The O. formigenes approach to treat PH is an ideal model for bacterial treatment of metabolic disease. The three SME participants will utilise the expertise of nine specialised research providers to increase the understanding of the characteristics of the sensitive, anaerobic and highly specialised O. formigenes, to implement the manufacturing process to obtain a clinically effective drug, to optimise drug delivery and to develop specialised analytical methods to monitor clinical effects following treatment. Technology advancements will be confirmed by clinical studies in PH patients and by mapping the presence of the bacteria before and after treatment with the O. formigenes drug. The ELIMOX project will advance current standards and methodology in i) manufacture of anaerobic bacteria for pharmaceutical use, ii) identification, quantification and tracking of microbes in the human gut and their impact on human microbiota during treatment, iii) optimisation of tools to monitor clinical effects during treatment with anaerobic bacteria.'

Introduzione (Teaser)

Primary hyperoxaluria (PH) is a rare and devastating disease resulting in renal failure and death at a young age. An EU consortium is developing a drug product based on Oxalobacter formigenes, to promote enteric elimination of oxalate through the gut and thereby protect the kidneys.

Descrizione progetto (Article)

PH is a rare disease caused by an inborn error in glyoxylate metabolism. Excessively high levels of endogenous oxalate in the urine and plasma of the patient cause end-stage renal disease and death around the age of 30. There is no approved pharmaceutical therapy in existence.

The EU-funded http://elimox.se/ (ELIMOX) (Biopharmaceutical therapy for treatment of primary hyperoxaluria) project is developing a treatment for PH. ELIMOX partners are creating a new drug from Oxalobacter formigenes, an anaerobic bacterium that uses oxalate as the only carbon source.

Enteric elimination of oxalate via the gut would provide an alternative elimination pathway for the oxalate, protecting the kidneys from failure. Treatment with pharmacological doses of O. formigenes would facilitate such enteric elimination.

This two year project involves 12 participating enterprises and universities; 11 participants are in five EU countries and one is in Canada. O. formigenes is a sensitive and highly specialised bacteria and considerable know-how and expertise are required to manufacture a clinically effective drug. The project has already developed and validated the lyophilisation, encapsulation and manufacturing processes. Three drug product batches have been produced to supply material for the clinical studies.

ELIMOX is not only optimising drug delivery but also developing analytical methods to monitor clinical effects following treatment. Assays for quantification of O. formigenes and for changes of gut flora have already been validated. They include time polymerase chain reaction (PCR) and the ion torrent personal genome machine.

Healthy volunteers have been used in a scintigraphy study to characterise capsule targeting. Enterically coated capsules survived in the stomach and started to disintegrate in the small intestine. ELIMOX partners are performing a number of clinical studies in PH patients, both with maintained renal function and on dialysis.

ELIMOX partners expect that study outcomes will demonstrate the safety and efficacy of their drug for PH treatment. The O. formigenes approach could also be adapted for treatment of metabolic disease.