The invention relates to an antibody which binds to myelin oligodendrocyte glycoprotein (MOG), an antibody fragment thereof, a hybridoma which produces the antibody or the antibody fragment, a nucleic acid containing a nucleotide sequence which encodes the antibody or the antibody fragment, a transformant cell containing a vector containing the nucleic acid, a method for producing the antibody or the antibody fragment, a composition containing the antibody or the antibody fragment and a method for detecting or measuring an antigen that is present in the brain, a method for diagnosing or treating a brain disease, a method for improving the property of an antibody of accumulating in the brain and a method for increasing the amount of an antibody in the brain which use the antibody or the antibody fragment.

Provided herein are polynucleotide sequences encoding human acid sphingomyelinase (SMPD1) and expression cassettes containing these coding sequences. Also provided are vectors, such as recombinant adeno-associated virus (rAAV) vectors having vector genomes that include an engineered SMPD1 coding sequence operably linked to one or more regulatory sequences. Further, compositions containing these expression cassettes and rAAV are provided, as well as methods for the use of these compositions for treatment of Niemann Pick Type A disease.

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.2C(?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.

Provided herein are fusion proteins that comprise an enzyme replacement therapy enzyme and an Fc region, as well as methods of using such proteins to treat a lysosomal storage disorder. Methods for transporting agents across the blood-brain barrier are also provided herein.

The present invention provides, inter alia, compositions and methods for using CB1 cannabinoid receptor agonists, or other compounds capable of increasing endocannabinoids or endocannabinoid signaling, for treating and preventing lysosomal storage disorders in which lipid storage occurs (including, e.g., disorders associated with sphingomyelin accumulation). In particular embodiments, the present invention provides compositions and methods for treating such lysosomal storage disorders with one or more fatty acid amide hydrolase inhibitor alone or in combination with one or more additional agent.

The present disclosure provides methods of screening, diagnosing, monitoring and/or treating acid sphingomyelinase (ASM) disorders such as Niemann-Pick disease. In particular, the methods encompass techniques for improved diagnosis and/or treatment of an ASM disorder, for example using enzyme replacement therapy.

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.

Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

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 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.2C(?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.