Kurzfassung

SuPerTurbo-ASA: novel therapeutic for the treatment of Metachromatic Leukodystrophy

Hintergrund

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficient activity of arylsulfatase A (ASA). ASA catalyzes the degradation of myelin lipid sulfatides. In patients suffering from MLD, sulfatides are not metabolized, accumulate strongly in cells of the nervous system and cause demyelination. Severe neurological symptoms are the result and lead to death. A treatment option for preserving neuronal integrity would be an enzyme replacement therapy by a double mutated and ApoEtagged version of ASA (SuPerTurbo-ASA).

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Lösung

SuPerTurbo-ASA is the subject-matter of two pending patent applications and can be licensed for the development and commercialisation of an enzyme replacement therapy for MLD patients.

SuPerTurbo-ASA has unique features, and a wide range of analyses has already been made. Most importantly SuPerTurbo-ASA is 8- to 12-fold more efficient in removing sulfatide storage from the central nervous system of MLD mice than wildtype ASA. Altered immunogenicity of SuPerTurbo-ASA has not been detected. This was investigated in a humanised mouse model of MLD with specific immunotolerance to human ASA. Repeated intravenous injections of recombinant human ASAwt or SuPerTurbo-ASA did not induce any side effect in this mouse model whereas murine ASAwt, used as a control, elicited anaphylactic reactions indicated by scratching, decreased cage activity and increased respiratory rate. This indicates that SuPerTurbo-ASA cannot be differentiated from human ASAwt by the murine immune system suggesting absence of novel epitopes