Pulsed introduction of low-dose RANKL as a therapy for diet-induced atherosclerosis

Patent metadata

Field	Value
Publication number	US-10745461-B2
Application number	US-201816126821-A
Country	US
Kind code	B2
Filing date	Sep 10, 2018
Priority date	Feb 25, 2015
Publication date	Aug 18, 2020
Grant date	Aug 18, 2020

Abstract

Systems and methods for inhibiting atherosclerosis using FoxP3+ CD8 T-cells (TcREG). Osteoclasts are induced to produce FoxP3+ CD8 T-cells (TcREG) through introduction of a low-dose of a RANK agonist such as RANKL. The RANKL was found to best work when provided in accordance with a schedule resulting in a pulsed administration.

First claim

The invention claimed is:

1. A method for inhibiting the onset of diet-induced atherosclerosis in a patient,
the method comprising:
providing said patient a RANK agonist being of:
sufficient amount to induce osteoclasts of said patient to produce FoxP3+ CD8 T− cells (Tc REG ); and
insufficient amount to activate enough of said osteoclasts to create new bone loss in said patient;

repeating said providing according to a fixed schedule so as to provide said RANK agonist to said patient at pulsed intervals, said patient having as a result of said fixed schedule increased bone mass compared to a patient not on said fixed schedule; and
not altering the patient's diet.

2. The method of claim 1 wherein said patient is a postmenopausal female.

3. The method of claim 1 wherein said patient is a male.

4. The method of claim 1 , wherein said RANK agonist is RANKL.

5. The method of claim 1 , wherein said low dose comprises 0.125 mg/kg RANKL or less.

6. The method of claim 1 , wherein said low dose comprises about 0.125 mg/kg RANKL.

7. The method of claim 1 , wherein said low dose comprises 0.05 mg/kg RANKL or less.

8. The method of claim 1 , wherein said low dose comprises 0.5 mg/kg RANKL or less.

9. The method of claim 1 , wherein the pulsed intervals are about once a month.

Assignees

• Univ Saint Louis

Inventors

• Aurora Rajeev
• Smith Anna
• Baldan Angel

Classifications

• A61K38/1793

  for cytokines; for lymphokines; for interferons · CPC title

• A61K38/191

  Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta · CPC title

• C07K14/70575 Primary

  NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525) · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title