Methods of modulating pericytes
Inventors
Assignees
Mallinckrodt Ard Ip Unlimited Co • Mallinckrodt Pharmaceuticals Ireland Ltd
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Publication Number
US-11752199-B1
Publication Date
2023-09-12
Expiration Date
Abstract
The present disclosure is directed to methods of modulating pericytes in subjects in need thereof.
Core Innovation
The invention provides methods of modulating pericytes and promoting new vessel formation in a subject in need thereof by administering an adrenal corticotropin treatment. After the administering, VCAM-1 expression and angiopoietin-2 expression are increased, linking adrenal corticotropin treatment to an endothelial activation marker profile associated with vascular remodeling and microvessel changes.
The described context includes vascular stability, including blood-brain barrier stabilization, together with pericyte-targeting outcomes such as increased pericyte number and pericyte longevity. The treatment is presented in relation to microvessels and biomarker readouts using VCAM-1, VEGF, Ang-2, and Glut-1+ vessels.
Adrenal corticotropin is defined to include synthetic or non-synthetic ACTH mimetics, including repository corticotropin injection as a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides. In particular, repository corticotropin injection is described as including N-25 deamidated porcine ACTH (1-39), and angiopoietin-2 expression reaches maximum after about 3 weeks of administration.
Claims Coverage
Two independent claims are identified. Both independent claims cover administering an adrenal corticotropin treatment to a subject to promote new vessel formation with increased VCAM-1 expression and increased angiopoietin-2 expression, including a temporal condition relating to 3 weeks for angiopoietin-2 increase/maximum.
Administering adrenal corticotropin treatment to increase VCAM-1 and angiopoietin-2
A method of promoting new vessel formation in a subject in need thereof, comprising administering an adrenal corticotropin treatment, wherein VCAM-1 expression and angiopoietin-2 expression is increased after the administering.
Administering adrenal corticotropin treatment with angiopoietin-2 increased following 3 weeks
A method of promoting new vessel formation in a subject in need thereof, comprising administering an adrenal corticotropin treatment, wherein VCAM-1 expression and angiopoietin-2 expression is increased following 3 weeks of administering the adrenal corticotropin.
Across both independent claims, the core claim coverage is centered on promoting new vessel formation by administering an adrenal corticotropin treatment and producing increased VCAM-1 expression and increased angiopoietin-2 expression, with one independent claim further tying the angiopoietin-2 increase to a 3-week time frame.
Stated Advantages
Promotes new vessel formation.
Increases VCAM-1 expression and angiopoietin-2 expression after administering adrenal corticotropin.
Provides vascular stability, including blood-brain barrier stabilization.
Increases pericyte number and pericyte longevity.
Documented Applications
Modulating pericytes and microvessels in a context that includes blood-brain barrier stabilization, with biomarker readouts using VCAM-1, VEGF, Ang-2, and Glut-1+ vessels.
A chronic cuprizone mouse model (CPZ model) showing increased vascular density after Acthar Gel treatment.
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