Edition of 22 September 2005

Primary Inherited Aminoacidurias (PIA) are rare diseases involving defects in renal absorption of amino acids. In cystinuria, for example, an autosomal recessive disorder, the kidneys do not adequately reabsorb certain amino acids (cystine, lysine, ornithine and arginine) during the filtering process, resulting in their excess excretion and the formation of painful crystals or stones in the kidney, urethra, or bladder.

The Eugindat project, funded under the EC’s 6th Framework programme (EU project number: LSHM-CT-2003-502852) aims to elucidate the genetic and molecular basis for these diseases and in doing so, develop new therapeutic strategies for their treatment.

Led by Dr Manuel Palacín of the University of Barcelona, the three-year Eugindat project brings together the expertise of 19 partners from 5 European countries and Israel, in a multidisciplinary approach integrating genetics, biochemistry, genomics, physiology, structural biology, drug development and clinical research. Two SMEs are also involved in the project.

One of the main objectives of the project is to develop a clinical and genetic description of Primary Inherited Aminoacidurias with the generation of a European database for PIA. This will include the study of candidate genes for cystinuria, dicarboxylic aminoaciduria, Hartnup disorder and iminoglycinuria. Information from the PIA database will be made available, at different levels of accessibility, for patients and patient associations, health professionals, contributing professionals and Eugindat members.

In addition, project partners will be looking at the molecular structure of relevant transporters for PIA and renal reabsorption of amino acids using 2D and 3D protein crystallography techniques, and completing a functional genomic study of these transporters using cellular and knockout mice models and the identification of polymorphisms in genetically isolated human populations.

By identifying genes and genetic loci that affect cystinuria lithiasis, they hope to eventually explain gender and individual variability in the formation of stones in the renal system of patients with cystinuria and to develop new therapeutic strategies for this disease.

One form of PIA disease, lysinuric protein intolerance (LPI), is associated with life-threatening complications of the immune system and can also affect the hepatic system. The Eugindat project aims to test new therapeutic approaches to treat the most severe effects of LPI once the mechanisms of pathology of these complications have been identified.

Although the Eugindat project deals principally with kidney function, the creation of mouse models of amino acid and peptide transporter defects will also have scientific impact in other areas, such as nutrition, cachexia (severe malnutrition associated with chronic illness) and certain disorders of the central nervous system, where these transporters play an important role.

Scientists, clinicians, patient organisations and institutions will be invited to attend a public meeting to be held in Rome in Spring 2007 to discuss the final results of the Eugindat project. For further details contact the Eugindat project office.