The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.

Compositions and methods for the treatment of muscular dystrophies are provided.

The present disclosure is directed to methods of treating a steatosis-associated disorder by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage.

The present invention relates to a method for treating degenerative neurological disorders in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising an acid sphingomyelinase (ASM) activity inhibitor or expression inhibitor as an active ingredient.

The invention relates to dose escalation enzyme replacement therapy using acid sphingomyelinase (ASM) for the treatment of human subjects having acid sphingomyelinase deficiency (ASMD), and, in particular, patients with non-neurological manifestations of Niemann-Pick Disease (NPD), and in certain embodiments, NPD type B.

The present invention provides an oxazole compound represented by Formula (1), or a salt thereof:

##STR00001##

wherein R.sup.1 is an aryl group which may have one or more substituents; R.sup.2 is an aryl group or a nitrogen atom-containing heterocyclic group each of which may have one or more substituents; and W is a divalent group represented by —Y.sup.1-A.sup.1- or —Y.sup.2—C(═O)— wherein Y.sup.1 is a group such as —C(═O)—, A.sup.1 is a group such as a tower alkylene group, and Y.sup.2 is a group such as a piperazinediyl group. The oxazole compound has a specific inhibitory action against phosphodiesterase 4.

The present invention provides a oxazole compound represented by Formula (1), or a salt thereof:

##STR00001##

wherein R.sup.1 is an aryl group which may have one or more substituents; R.sup.2 is an aryl group or a nitrogen atom-containing heterocyclic group each of which may have one or more substituents; and W is a divalent group represented by —Y.sup.1-A.sup.1- or —Y.sup.2—C(═O)— wherein Y.sup.1 is a group such as —C(═O)—, A.sup.1 is a group such as a lower alkylene group, and Y.sup.2 is a group such as a piperazinediyl group. The oxazole compound has a specific inhibitory action against phosphodiesterase 4.

The present disclosure is directed to methods of treating a steatosis-associated disorder and methods of treating a cytoplasmic glycogen storage disorder, including glycogen storage disease I, glycogen storage disease III, glycogen storage disease IV, and/or conditions associated with a PRKAG2 mutation, by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage. Methods of treating a cytoplasmic glycogen storage disorder by administering a lysosomal enzyme and a second therapeutic agent are also described. Other embodiments are directed to methods of treating a cytoplasmic glycogen storage disorder by administering a therapeutic agent as an adjunctive therapy to lysosomal enzyme replacement therapy.

The invention provides methods for the synthesis of oligosaccharides comprising an aminooxy group. The invention further provides oligosaccharides comprising an aminooxy group, methods for coupling oligosaccharides comprising an aminooxy group to glycoproteins, and oligosaccharide-protein conjugates. Also provided are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-protein conjugate.

The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.