Reagents, methods, and kits for assaying enzymes associated with lysosomal storage diseases MPS-I, MPS-II, MPS-IIIA, MPS-IIIB, MPS-IVA, MPS-VI, and MPS VII.

Provided is a ultra-high-sensitivity assay in which the assay can be made on a commonly used assay apparatus such as an absorptiometer and a plate reader or with naked eyes. The high-sensitivity assay in which the assay can be made on a commonly used assay apparatus or with naked eyes can be provided by combining an enzyme cycling method using thio-NAD(P) as a coenzyme, a labeling enzyme and a substrate for the labeling enzyme optimally, and by amplifying thio-NAD(P)H, which is a signaling substance, exponentially and then quantifying the thio-NAD(P)H colorimetrically.

Described herein are systems and methods for extending the dynamic range of assay methods and systems used for determining the concentration of analyte molecules or particles in a fluid sample. In some embodiments, a method comprises spatially segregating a plurality of analyte molecules in a fluid sample into a plurality of locations. At least a portion of the locations may be addressed to determine the percentage of said locations containing at least one analyte molecule. Based at least in part on the percentage, a measure of the concentration of analyte molecules in the fluid sample may be determined using an analog, intensity-based detection/analysis method/system and/or a digital detection/analysis method/system. In some cases, the assay may comprise the use of a plurality of capture objects.

The present disclosure provides technologies relating to lysosomal activation. The disclosure provides several strategies for increasing level and/or activity of lysosomal enzyme, and furthermore demonstrates the surprising applicability of such strategies in the treatment and/or prophylaxis of certain proteinopathies. Among other things, the present invention provides methods and compositions for the treatment and/or prophylaxis of proteinopathies other than lysosomal storage diseases through lysosomal activation. In particular, the present disclosure provides methods and compositions for the treatment and/or prophylaxis of neurodegenerative proteinopathies, and in particular those associated with accumulation of α-synuclein. The present disclosure specifically provides methods and compositions for the treatment and/or prophylaxis of Parkinson's disease.

The present disclosure provides methods for monitoring subject (e.g., patient) adherence to quetiapine therapy, for example as a component of treating a subject for a mental health disorder such as schizophrenia, bipolar disorder or major depressive disorder.

Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile.

The present disclosure provides methods of determining whether a subject treated for hypertension should continue hypertension treatment. In exemplary embodiments, the method comprises measuring the level of at least two of the following in a urine sample obtained from the subject: (i) Alpha—1 microglobulin (aim); (ii) kidney injury molecule (KIM—1); and (iii) Chitinase-3-like protein (YKL-40); wherein the subject should continue the hypertension treatment, when the levels are decreased or unchanged, relative to a control level, and wherein the subject should discontinue or decrease the hypertension treatment, when the levels are increased, relative to a control level. Related methods, kits, assay systems, systems comprising machine readable instructions, computer-readable storage media, and methods implemented by a processor in a computer are furthermore provided herein.

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38.sup.30 cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic rnyelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38, Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

Provided is a high-accuracy analysis method utilizing an enzyme-lined immunoassay. The presence of an analyte 3 can be detected or the abundance of the analyte 3 can be analyzed by: bonding an antibody 5 that is capable of specifically bonding to the analyte 3 immobilized on a solid phase 1 and has an enzyme 7 bonded thereto; then decomposing an enzyme substrate 8, which can generate decomposition products capable of being detected easily with a mass spectrometry, with the enzyme 7 bonded to the antibody 5; and then analyzing the decomposition products 9 and 10 with a mass spectrometry.

A biomass containment device (BCD) and methods of measuring microbial growth or enzyme activity in the presence of insoluble substrates using the BCD is described. The BCD is compatible with microbial growth and enzyme assays, is sterilizable, is reusable, and the size can be varied to fit any container.