Methods for treating and/or limiting development of diabetes
Inventors
Berggren, Per Olof • Yang, Shao-Nian
Assignees
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Publication Number
US-10226530-B2
Publication Date
2019-03-12
Expiration Date
Abstract
The present invention provides methods for identifying candidate compounds for limiting development of and/or treating diabetes, and methods for limiting development of and/or treating diabetes.
Core Innovation
The patent describes a diabetes/drug-discovery framework centered on apolipoprotein CIII (ApoCIII)-mediated hyperactivation of pancreatic β-cell Cav1 channels. In this framework, insulin-secreting cells are exposed to ApoCIII together with test compounds, and assay positives are those that block ApoCIII-induced increases in Cav1 channel density and/or conductivity. The framework is focused on Cav1 channels in pancreatic β cells, including Cav1.2 and Cav1.3.
The disclosed mechanistic and therapeutic targets include αβ21 integrin, PKA, and Src kinase in the context of ApoCIII-induced Cav1 hyperactivation. The document indicates use of controls involving CaV2/3 blockers and kinase/integrin inhibitors, linking interruption of these pathways to reduced ApoCIII effects. The patent further associates ApoCIII with increases in Cav1 activity and currents while distinguishing effects on channel density and/or conductivity.
The document reports experimental findings showing ApoCIII increases single-channel and whole-cell Cav1 activity and currents, and that nimodipine abrogates the effect. It also states that combined PKA/Src inhibition and PKA+PKC+Src inhibition counter ApoCIII-induced Cav1 hyperactivation. The patent additionally reports that ApoCIII does not alter Cav1.2/Cav1.3 expression, and that αβ21 integrin knockdown prevents ApoCIII-induced Cav1 hyperactivation.
Claims Coverage
The partial content identifies one independent claim. That claim contains a single core inventive approach: administering an anti-αβ21 integrin antibody to treat or limit development of diabetes, with dependent claims further refining the diabetes context, subject type, and a condition involving ApoCIII overexpression relative to a control.
Anti-αβ21 integrin antibody for treating or limiting diabetes development
Administering to a subject in need thereof an amount effective of an anti-αβ21 integrin antibody to treat or limit development of diabetes.
Across the identified claim set, the inventive core is the use of an anti-αβ21 integrin antibody administered in an effective amount to treat or limit development of diabetes, with dependent features specifying treating vs limiting development, type 1 versus type 2 diabetes subject contexts, and subject characterization by ApoCIII overexpression relative to a control.
Stated Advantages
Treating or limiting development of diabetes.
Documented Applications
A diabetes/drug-discovery screening framework using insulin-secreting cells exposed to ApoCIII plus test compounds to identify compounds that block ApoCIII-induced Cav1 hyperactivation by reducing increases in Cav1 channel density and/or conductivity.
Mechanistic/therapeutic context for administering inhibitors related to PKA/Src, αβ21 integrin expression/activity, or inhibitors of ApoCIII activation/binding in connection with ApoCIII-induced Cav1 hyperactivation in pancreatic β cells.
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