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The HUE-MAN Project

Towards The Development Of An Effective Enzyme Replacement Therapy For Human Alpha-Mannosidosis


Project summary

Alpha-Mannosidosis is a rare inborn disorder caused by the lack of the lysosomal enzyme α-Mannosidase, resulting in mental retardation, skeletal changes, hearing loss and recurrent infections. The children are often born apparently normal, and their conditions worsen progressively, without any possibility to prevent this evolution. In the children that are born healthy, a therapy initiated at an early age could contribute to a normal development. Today, the most promising therapy for lysosomal storage disorders is enzyme replacement therapy (ERT); where the enzyme lacking in the patient is introduced into the blood stream, from where it is internalised by the cells and reaches the lysosomes, acting as the endogeneous enzyme. ERT products are on the market today for diseases such as Gaucher and Fabry and clinical trials are underway for a number of other diseases. Within FP5 the collaborative research project EURAMAN successfully established an enzyme replacement therapy for a mouse model of Alpha-Mannosidosis. A correction of storage in many tissues including brain was found after administration of lysosomal acid á-Mannosidase (LAMAN) from bovine kidney, and human and mouse recombinant LAMAN. The main objective of the HUE-MAN project is to transfer and expand the knowledge obtained from the EURAMAN project studies to investigate and establish clinical parameters in the mouse model and a natural history study of the human disease in order to define clinical endpoints for the future clinical trials in á-Mannosidosis. Furthermore, in parallel, HUE-MAN will establish conditions for the production of rhLAMAN that can pave the way for a First Clinical Trial in Man.

Project objectives

In view of the need to get an causative cure for the human disease and taking into account the promising data on enzyme replacement therapy using human recombinant LAMAN in the mouse model the current project will bring together cell and molecular biologists, clinicians with regular patient contact, neuropharmacologists with expertise in behavioural analysis, epidemiologists and biochemists with experience in large scale enzyme production and toxicology testing to set up the conditions and knowledge for eventually introducing the reLAMAN drug into first clinical trials. The unique composition and collection of expertises of his consortium will be of major importance to pave the way for a successful introduction of ERT for human patients suffering from Alpha-Mannosidosis. The ultimate aim will be to push forward the development a high quality, safe and effective drug.