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A life-saving therapy for severe hyperammonemia
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Coopération
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.
Données de projet
- Numéro du projet: GRS-053/14
- Subside accordé: CHF 320'000
- Consentement: 23.01.2015
- Durée: 06.2015 - 02.2017
- Champs d'activité: Pilotprojekte, 1998 - 2018
Direction du projet
- Dr. Vincent Forster
- ETH Zürich
- Institute for Pharmaceutical Sciences
- Vladimir-Prelog-Weg 1-5/10
- 8093 Zürich (Schweiz)
- vincent.forster@pharma.ethz.ch
Description du projet
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.
Quelles sont les particularités de ce projet?
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.
Etat/résultats intermédiaires
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.
Publications
Revue de presse
Liens
Personnes participant au projet
Dernière mise à jour de cette présentation du projet 27.04.2021