Methods for treating and/or limiting development of diabetes in subjects with amyotrophic lateral sclerosis

Inventors

Berggren, Per-Olof

Assignees

Biocrine AB

Abstract

Methods for treating and/or limiting development of diabetes in a subject with amyotrophic lateral sclerosis (ALS) by inhibiting IgG-mediated activation of voltage-gated calcium channels (VGCCs) in cells of the subject, by one or more of removing IgG from blood of the subject, blocking IgG from activating VGCCs in the subject; or blocking VGCCs in the subject are described, as are methods for identifying ALS patients at risk of developing diabetes.

Core Innovation

The disclosed invention relates to treating diabetes in a subject with amyotrophic lateral sclerosis (ALS) by inhibiting IgG-mediated activation of voltage-gated calcium channels (VGCCs) in cells of the subject. The inhibiting comprises blocking VGCCs in the subject, so that IgG-mediated activation of the VGCCs is reduced in the subject’s cells.

Inhibiting VGCCs is achieved by blocking VGCC expression or activity through administration of a VGCC expression/activity inhibitor. The disclosure identifies Ca2+ channel blockers and VGCC-specific antibodies, together with aptamers and nucleic-acid-based inhibitors, including siRNAs, microRNAs, shRNAs, and antisense oligonucleotides.

The disclosure also links ALS-associated IgG to altered Ca2+ handling and disturbed glucose homeostasis, and states that ALS-Tg and ALS serum/T2DM-associated ALS IgG induce disturbed glucose homeostasis, altered Ca2+ handling, impaired insulin secretion, and reduced islet or alpha-cell viability. Specific L-type VGCC blockade attenuates these effects, and boiling ALS-IgG reduces activity.

Claims Coverage

The independent claim family contains 1 independent claim (clm-00001). The main coverage is a treatment method for diabetes in an ALS subject by inhibiting IgG-mediated activation of VGCCs, with dependent claims refining how VGCCs are blocked, which inhibitor classes are selected, and which diabetes type is addressed (type 1 or type 2).

Overall, the claims cover treating diabetes in an ALS subject by inhibiting IgG-mediated activation of VGCCs through blocking VGCCs, with refinements that specify administration of VGCC expression/activity inhibitors, selection from Ca2+ channel blockers and VGCC-specific antibodies, aptamers, and nucleic-acid-based inhibitors, chemical-class narrowing, and specification of diabetes type (type 1 or type 2).

Stated Advantages

Documented Applications