Abstract: As described herein, lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). LacCer acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS infiltrating monocytes and microglia, and neurodegeneration. In addition, increased B4GALT6 expression and LacCer levels were detected in CNS MS lesions in human patients. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a therapeutic target for MS and other neuroinflammatory disorders.

Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a glioma. Methods of this invention include administering to a subject in need thereof an effective amount of a first active agent, such as e.g., an angiotensin receptor blocker, an antifungal agent, a bisphosphonate, an oxytocin inhibitor, an interleukin-1 (IL-1) inhibitor, a cyclooxygenase inhibitor, an ?2? voltage-dependent calcium channel (VDCC) inhibitor, a dihydroorotate dehydrogenase inhibitor, a calcium channel blocker, a renal sodium-chloride symporter inhibitor, an a2 adrenergic agonist, a phenothiazine antipsychotic, a calcineurin inhibitor, a 5-HT agonist, an angiotensin-converting enzyme (ACE) inhibitor, a direct rennin inhibitor, or combinations thereof, and a second active agent, which is a chemotherapeutic agent. Compositions for treating or ameliorating the effects of a glioma are also provided.

Abstract: As described herein, lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). LacCer acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS infiltrating monocytes and microglia, and neurodegeneration. In addition, increased B4GALT6 expression and LacCer levels were detected in CNS MS lesions in human patients. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a therapeutic target for MS and other neuroinflammatory disorders.

Abstract: The present invention provides, inter alia, compositions containing enantiomerically pure (R)(+)-amisulpride or enantiomerically pure (R)(+)-sulpiride, optionally with dopamine receptor modulators. The present invention also provides compositions containing racemic (RS)-amisulpride or (RS)-sulpiride in combination with dopamine receptor modulators. Methods for preventing, treating, or ameliorating the effects of a metabolic disorder or key element thereof, for modulating blood glucose levels, and for preventing, treating, or ameliorating the effects of diabetes in a subject are also provided. Additionally, the present invention provides methods for counter-acting the dopamine antagonist activity of (S)-amisulpride in racemic (RS)-amisulpride, or the dopamine antagonist activity of (S)-sulpiride in racemic (RS)-sulpiride, administered to a subject to prevent, treat, or ameliorate the effects of a metabolic disorder.

Abstract: The present invention provides, inter alia, methods for treating or ameliorating the effects of a glioma. Methods of this invention include administering to a subject in need thereof an effective amount of a first active agent, such as e.g., an angiotensin receptor blocker, an antifungal agent, a bisphosphonate, an oxytocin inhibitor, an interleukin-1 (IL-1) inhibitor, a cyclooxygenase inhibitor, an ?2? voltage-dependent calcium channel (VDCC) inhibitor, a dihydroorotate dehydrogenase inhibitor, a calcium channel blocker, a renal sodium-chloride symporter inhibitor, an a2 adrenergic agonist, a phenothiazine antipsychotic, a calcineurin inhibitor, a 5-HT agonist, an angiotensin-converting enzyme (ACE) inhibitor, a direct rennin inhibitor, or combinations thereof, and a second active agent, which is a chemotherapeutic agent. Compositions for treating or ameliorating the effects of a glioma are also provided.