Abstract: The present invention provides compounds having a structure according to Formula I: (I) or a salt or solvate thereof, wherein R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Abstract: The invention relates to the treatment of disorders associated with elevated myo-inositol levels in brain, in particular behavioural and neuropsychiatry disorders such as dementia, mild Alzheimer's disease, mild cognitive impairment or bipolar disorder by administering an effective amount of scyllo-inositol to a subject.

Abstract: The invention relates generally to novel compositions and methods comprising a scyllo-inositol compound and one or both of valproic acid compound and lamotrigine. The compositions and methods provide beneficial effects in the treatment of bipolar disorders.

Abstract: The invention provides methods of screening for agents useful in treating or prophylaxis of synucleinopathic disease, methods of diagnosis or prognosis of the same and methods of treatment and prophylaxis. The invention is based in part on the result that cells with phagocytic activity from subjects with synucleinopathic disease have increased levels of alpha synuclein and reduced phagocytic activity and that these processes can be reversed (i.e., synuclein levels decreased and phagocytic levels increased) by treatment with IL-4 among other agents. The increase in phagocytic activity is readily amenable to detection and provides a basis for a screening assay in which an agent is contacted with phagocytic cells and the effect of the agent on phagocytic activity is detected, which is an indicator that the agent has the ability to reduce alpha synuclein levels.

Abstract: The present disclosure relates to compositions and methods for reducing uric acid levels in a individual in need thereof. The present disclosure further relates to the treatment of hyperuricemia and diseases associated with high uric acid levels in mammals using scyllo-inositol.

Abstract: Methods useful for effecting prophylaxis or treatment of amyloidosis, including AA Amyloidosis and AL amyloidosis, by administering peptides comprising neoepitopes, such as AA fragments from a C-terminal region of AA, and antibodies specific for neoepitopes of aggregated amyloid proteins, for example, antibodies specific for the C-terminal region of AA fibrils. Antibodies for inhibition of formation and/or increasing clearance of amyloid deposits in a patient thus effecting prophylaxis or treating amyloid disease.

Abstract: Disclosed is a process for preparing polymer conjugates of agricultural, therapeutic, and food additive compounds using Mitsunobu conditions.

Abstract: Alpha 4 inhibitors are used in treatment of inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn's Disease, rheumatoid arthritis and asthma. Rare occurrences of progressive multifocal leucoencephalopathy during treatment with an alpha-4 agent suggest the possibility that it may be related to such treatment. Monitoring for the JC virus and educating caregivers and patients about the manifestations of progressive multifocal leucoencephalopathy can improve the safety of alpha 4 inhibitor therapy.

Abstract: Disclosed are conjugates which bind VLA-4. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such conjugates are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The invention provides methods for detecting alpha-synuclein. The invention also identifies preferred epitopes of alpha synuclein for use in such detection, and provides antibodies specifically binding to such epitopes.

Abstract: Disclosed is a process for preparing polymer conjugates of agricultural, therapeutic, and food additive compounds using Mitsunobu conditions.

Abstract: The present invention provides compounds that are alpha4 integrin antagonists having a structure according to the following formula: or a tautomer, mixture of tautomers, salt or solvate thereof, wherein Cy, ring A, m, n, p, R1, R2, R3, R4, R5 and R6 are defined in the specification. The invention further provides pharmaceutical compositions including the compounds of the invention as well as methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various conditions and disorders, such as Crohn's disease and ulcerative colitis.

Abstract: The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, E1, E2, R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Abstract: The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Abstract: The invention provides transgenic animals having a transgene comprising a genomic human alpha synuclein segment including six exons, five introns and at least one mutation associated with synucleinopathic disease operably linked to a human alpha synuclein promoter. The transgenic animals have characteristics of synucleinopathic disease including elevated levels of alpha synuclein in the brain, formation of intracellular deposits of alpha synuclein that have at least one, and preferably all features of Lewy bodies, formation of alpha-synuclein fragments, or phosphorylated forms of alpha synuclein, loss of neuronal cells, glial cells or oligodentricytes, impairment of motor function and/or impairment of cognitive function.

Abstract: The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

Abstract: The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Abstract: Alpha 4 inhibitors are used in treatment of inflammatory and autoimmune diseases, such as multiple sclerosis, Crohn's Disease, rheumatoid arthritis and asthma. Rare occurrences of progressive multifocal leucoencephalopathy during treatment with an alpha-4 agent suggest the possibility that it may be related to such treatment. Monitoring for the JC virus and educating caregivers and patients about the manifestations of progressive multifocal leucoencephalopathy can improve the safety of alpha 4 inhibitor therapy.

Abstract: The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

Abstract: The invention provides method of treatment using humanized immunoglobulins that specially bind to alpha-4 integrin. The methods are useful for treatment of asthma, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, transplant rejection, graft versus host disease, tumor metastasis, nephritis, atopic dermatitis, psoriasis, myocardial ischemia, and acute leukocyte mediated lung injury.