Relevance to the objectives of the EU call and topic

The project applies to the call HEALTH-2007-2.4.4. – Rare diseases whose expected impact is ” (i) to shed light on the course and/or mechanisms of rare diseases, or (ii) to test diagnostic, preventive and/or therapeutic approaches, to alleviate the negative impact of the disease on the quality of life of the patients and their families”.

The health theme specifically plans to contribute to research into rare diseases: “The focus will be on Europe-wide studies of natural history, pathophysiology and on development of preventive, diagnostic and therapeutic interventions. This sector will include rare Mendelian phenotypes of common diseases”.
The interest of the EUCLYD consortium is the study of Lysosomal Storage Disorders (LSDs), a heterogeneous group of disorders that encompass more than 40 distinct metabolic diseases. The incidence of LSDs as a group is 1:5000-1:8000, but, taken individually, each disease is very rare and many have an incidence of less than 1:100,000. However, one important peculiarity of LSDs is that data indicate that the basis of the diseases and pathogenetic mechanisms of the symptoms may have common grounds; therefore, the study of a few more relevant examples, such as Gaucher Disease, Pompe Disease, Mucopolysaccharidosis VI (MPS VI) and Multiple Sulfatase Deficiency (MSD), may have huge implications for the entire group of disorders.

The EUCLYD consortium plans to address the topic HEALTH-2007-2.4.4-1: Natural course and pathophysiology of rare diseases through the development of the following experimental plan:
In WP1, the consortium will study the pathophysiology of MSD, Gaucher Disease and MPS VI. These studies will unveil the basic mechanisms to explain disease phenotype. This knowledge will allow developing therapies to contrast the devastating effects of accumulation, and to understand whether and when therapies should be devised. In WP2, research will be focused on the natural history of Gaucher Disease, Pompe Disease and MPS VI. The study of the natural history of these disorders is essential to evaluate the effectiveness of therapy. Novel therapeutic strategies for LSDs consist of the application of small molecules that inhibit substrate synthesis, known as substrate reduction (WP3), or small molecules that act as chaperones to increase the residual activity of the lysosomal enzymes, known as enzyme enhancement therapy (WP4). Finally, the consortium will test and develop new protocols utilizing Adeno-Associated Virus (AAV) vectors to directly administer the wild-type gene into a factory organ taking advantage of normal lysosomal enzyme trafficking and a phenomenon known as “cross-correction” (WP5).