Abstract: Embodiments herein include variants of ?-hexosaminidase that are useful for hydrolyzing GM2 ganglioside, polynucleotides encoding the same, and related methods. In various embodiments, a variant ?-hexosaminidase subunit is included wherein the variant ?-hexosaminidase subunit forms a homodimer under physiological conditions and wherein the variant ?-hexosaminidase subunit associates with GM2 activator protein to hydrolyze GM2 ganglioside. In some embodiments, an isolated or recombinant polynucleotide encoding such a variant ?-hexosaminidase subunit is included. In some embodiments, a method of treating a subject exhibiting an abnormal cellular accumulation of GM2 ganglioside is included wherein the method includes administering a composition including a protein variant of ?-hexosaminidase or a polynucleotide encoding the same. Other embodiments are included herein.

Abstract: A method of treating a lysosomal storage disease comprises administering a pyrimethamine derivative to a subject in need thereof.

Abstract: Embodiments herein include variants of ?-hexosaminidase that are useful for hydrolyzing GM2 ganglioside, polynucleotides encoding the same, and related methods. In various embodiments, a variant ?-hexosaminidase subunit is included wherein the variant ?-hexosaminidase subunit forms a homodimer under physiological conditions and wherein the variant ?-hexosaminidase subunit associates with GM2 activator protein to hydrolyze GM2 ganglioside. In some embodiments, an isolated or recombinant polynucleotide encoding such a variant ?-hexosaminidase subunit is included. In some embodiments, a method of treating a subject exhibiting an abnormal cellular accumulation of GM2 ganglioside is included wherein the method includes administering a composition including a protein variant of ?-hexosaminidase or a polynucleotide encoding the same. Other embodiments are included herein.

Abstract: A method of treating a lysosomal storage disease comprises administering a pyrimethamine derivative to a subject in need thereof.

Abstract: A method is provided for determining the activity of an enzyme which releases methylumbelliferone (MU) from an MU-containing substrate wherein the enzyme has a pH optimum below the pKa of MU comprising: contacting a sample suspected of containing the enzyme with the MU-containing substrate at a pH suitable for activity of the enzyme to allow release of MU by the enzyme; contacting the sample with light of a wavelength in the range of about 310 nm to about 350 nm; determining fluorescence produced by the released MU, thereby determining the activity of the enzyme. This real time method provides improved diagnostic methods, for example for diseases associated with an abnormal level of activity of a glycosidase. The real time assay also can be used to screen compounds for their ability to modulate enzyme activity using MU-containing substrates.

Abstract: The invention provides methods and compositions for increasing Na ion transport and/or epithelial fluid transport in a vertebrate by administering an effective amount of haptoglobin or haptoglobin and hemoglobin. The invention also provides a new therapeutic approach for treating disorders associated with insufficient epithelial Na ion and/or fluid transport, the use of an effective amount of haptoglobin, or haptoglobin and hemoglobin in the preparation of medicament for increasing epithelial Na ion transport in a vertebrate as well as a method of screening a candidate compound for its ability to modulate haptoglobin or haptoglobin and hemoglobin stimulation of epithelial Na ion transport.

Abstract: The invention provides a method for treating an animal suffering from a disease associated with reduced activity of a lysosomal hexosaminidase by administering to the animal an effective amount of a compound which increases the activity of the hexosaminidase.

Abstract: A method is provided for determining the activity of an enzyme which releases methylumbelliferone (MU) from an MU-containing substrate wherein the enzyme has a pH optimum below the pKa of MU comprising: contacting a sample suspected of containing the enzyme with the MU-containing substrate at a pH suitable for activity of the enzyme to allow release of MU by the enzyme; contacting the sample with light of a wavelength in the range of about 310 nm to about 350 nm; determining fluorescence produced by the released MU, thereby determining the activity of the enzyme. This real time method provides improved diagnostic methods, for example for diseases associated with an abnormal level of activity of a glycosidase. The real time assay also can be used to screen compounds for their ability to modulate enzyme activity using MU-containing substrates.

Abstract: An anti-inflammatory composition is provided. The composition comprises GM2 activator protein or a peptide derived from the GM2 activator protein which is capable of inhibiting platelet activating factor (PAF). The composition is useful in the treatment of inflammatory conditions such as inflammatory bowel disease and asthma.