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Every project supported by Gebert Rüf Stiftung is made accessible with a web presentation that informs about the core data of the project. With this public presentation, the foundation publishes the funding results achieved and contributes to the communication of science to society.
A life-saving therapy for severe hyperammonemia
Editorial
Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.
Cooperation
Dieses von der Gebert Rüf Stiftung geförderte Projekt wird von folgenden weiteren Projektpartnern mitgetragen: Versantis AG, Drug Formulation & Delivery Group, ETH Zurich; Venture Kick, St. Gallen; Volkswirtschaftstiftung, Zürich; The Comission for Technology and Innovation, Bern; Zürcher Kantonalbank, Zürich.
Project data
- Project no: GRS-053/14
- Amount of funding: CHF 320'000
- Approved: 23.01.2015
- Duration: 06.2015 - 02.2017
- Area of activity: Pilotprojekte, 1998 - 2018
Project management
- Dr. Vincent Forster
- ETH Zürich
- Institute for Pharmaceutical Sciences
- Vladimir-Prelog-Weg 1-5/10
- 8093 Zürich (Schweiz)
- vincent.forster@pharma.ethz.ch
Project description
The liver is the largest organ in the body and plays a crucial role in eliminating toxins (waste products of metabolism, drugs…) circulating in the blood. Ammonia is a metabolic toxin generated by the digestion of proteins and is extremely harmful when present above physiological levels. Being normally metabolized by the liver and eliminated via the kidneys, any deterioration in hepatic functions causes a toxic ammonia accumulation (i.e., hyperammonemia), rapidly leading to severe brain injuries and death. The prevalence of hyperammonemia increases dramatically each year. It is driven by the increase of liver diseases, which is estimated to affect 10-50% of all Western populations and approximately 450 million people worldwide.
The only cure for severe hepatic failure with hyperammonemia is liver transplantation. Today, hemodialysis-based supportive systems are used as bridge therapies until a donor organ is available for transplantation. However, most of these system are not adapted to remove hepatic toxins and despite great efforts expended on the development of specific liver dialysis, they remain complex, expensive, and their efficacy is inconclusive.
The only cure for severe hepatic failure with hyperammonemia is liver transplantation. Today, hemodialysis-based supportive systems are used as bridge therapies until a donor organ is available for transplantation. However, most of these system are not adapted to remove hepatic toxins and despite great efforts expended on the development of specific liver dialysis, they remain complex, expensive, and their efficacy is inconclusive.
What is special about the project?
Versantis develops an innovative peritoneal dialysis (PD) fluid containing microvesicles (i.e. liposomes) that by actively trapping ammonia enhance its clearance from the body. This liposomes-supported PD (LSPD) relies on the well-known PD procedure that is accessible in any hospital and can be implemented in any patients, even the severely diseased cases or the neonates.
Our technology has a tremendous potential as a detoxification therapy in patients with liver disease and more generally as a versatile antidote against exogenous intoxications (e.g., drug overdoses). It is using an innovative approach which will open up new areas in the field of liver dialysis.
Our technology has a tremendous potential as a detoxification therapy in patients with liver disease and more generally as a versatile antidote against exogenous intoxications (e.g., drug overdoses). It is using an innovative approach which will open up new areas in the field of liver dialysis.
Status/Results
We have developed a robust LSPD product, de-risked in terms of safety, efficacy and manufacturing process, setting the basis for its clinical translation. To achieve this goal an innovative method for a rapid on-site preparation and facilitate manufacturing was established. The safety and efficacy of the final product was assessed in several animal species and models, including the gold-standard rodent model of liver cirrhosis (bile duct ligated rats). In this model, LSPD outperforms conventional peritoneal dialysis in lowering plasmatic ammonia levels and attenuating brain edema. In addition, we showed that LSPD does not trigger any hypersensitive reaction in pigs, a side effect commonly observed upon the injection of colloids in this animal model and in humans. The outcomes of this project support the clinical potential of LSPD which stands out as the sole answer to the unmet medical needs of patients suffering from acute liver diseases.
The next steps towards the clinical development of LSPD will be carried out by the pharmaceutical company Versantis. In 2017, the company plans to complete the regulatory repeated toxicology investigations in large animals in view of a first trial in patients in 2018.
The next steps towards the clinical development of LSPD will be carried out by the pharmaceutical company Versantis. In 2017, the company plans to complete the regulatory repeated toxicology investigations in large animals in view of a first trial in patients in 2018.
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Persons involved in the project
Last update to this project presentation 27.04.2021