Multimeric protein structures comprising at least two alpha-galactosidase monomers being covalently linked to one another via a linking moiety are disclosed herein, as well a process for preparing same, and methods of treating Fabry disease via administration of a multimeric protein structure. The disclosed multimeric protein structures exhibit an improved performance, in terms of enhanced activity and/or a longer lasting activity under both lysosomal conditions and in a serum environment.

Provided are methods for treatment of Fabry disease in a patient having renal impairment. Certain methods comprise administering to the patient about 100 mg to about 300 mg free base equivalent of migalastat or salt thereof at a frequency of greater than once every other day, such as once every four or seven days. Certain methods comprise measuring lyso-Gb3 and/or migalastat in one or more plasma samples from the patient.

The invention relates to an affinity resin functionalized with small molecule inhibitors of glycoside-cleaving enzymes, e.g., α-galactosidase A (α-Gal A), glucocerebrosidase (GCB), β-galactosidase, and acid alpha-glucosidase (GAA), and a method for purifying glycoside-cleaving enzymes produced in a cell line using the small molecule inhibitor-functionalized affinity resin.

The present invention provides engineered human alpha-galactosidase polypeptides and compositions thereof. The engineered human alpha-galactosidase polypeptides have been optimized to provide improved stability under both acidic (pH <4.5) and basic (pH >7) conditions. The invention also relates to the use of the compositions comprising the engineered human alpha-galactosidase polypeptides for therapeutic purposes.

The present disclosure provides codon optimized nucleotide sequences encoding human alpha-galactosidase A, vectors, and host cells comprising codon optimized alpha-galactosidase A sequences, and methods of treating disorders such as Fabry disease comprising administering to the subject a codon optimized sequence encoding human alpha-galactosidase A.

The present invention relates to a lysosomal protein composition comprising a plurality of lysosomal proteins that are potentially diversely glycosylated according to a glycosylation pattern, wherein said glycosylation pattern has at least 45% paucimannosidic N-glycans; a method of manufacturing the lysosomal protein composition in a bryophyte plant or cell, and medical and non-medical uses of the lysosomal protein composition. E.g. the lysosomal protein can be α-Galactosidase for the treatment of Fabry Disease or β-Glucoceramidase for the treatment of Gaucher's Disease. The unique glycosylation results in improved therapeutic efficacy—surprisingly even without mannose-6-phosphate that is common for CHO cell produced lysosomal proteins.

The present invention relates to uses of at least one carbohydrase in combination with an animal feed with a defined A/X fiber fraction, to an animal feed with a defined A/X fiber fraction and comprising at least one carbohydrase in an amount determined suitable to the A/X fiber fraction of the feed and methods of making thereof.

Disclosed herein are compositions and methods for modulatimi the production of a protein in a target cell, The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

The present invention provides engineered human alpha-galactosidase polypeptides and compositions thereof. The engineered human alpha-galactosidase polypeptides have been optimized to provide improved thermostability, serum stability, improved cellular uptake, stability under both acidic (pH<4) and basic (pH>7) conditions, reduced immunogenicity, and improved globotriaosylceramide removal from cells. The invention also relates to the use of the compositions comprising the engineered human alpha-galactosidase polypeptides for therapeutic purposes.

Compositions for modulating the expression of a protein in a target cell comprising at least one RNA molecule which comprises at least one modification 5 conferring stability to the RNA, as well as related methods, are disclosed.