Methods for modulating autophagy using remote ischemic conditioning

• US 10,272,241 B2
• Filed: 03/14/2014
• Issued: 04/30/2019
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Hospital For SICK Children
• Original Assignee: Hospital For SICK Children
• Inventors: Redington, Andrew
• Primary Examiner(s): Hulbert, Amanda K
• Application Number:
  US14/774,835
• Publication Number:
  US 20160045726A1
• Time in Patent Office: 1,873 Days
• CPC Class Codes: A61B 17/1204 temporary occlusion
• CPC Class Codes: A61B 17/132 Tourniquets sphygmomanometer A61B5/022
• CPC Class Codes: A61B 17/135 inflatable for measuring blood pressure A61B5/022; inflatable pressure pads A61F5/34
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention contemplates, inter alia, the use of remote ischemic conditioning in the treatment of cancer, neurodegenerative disorders, and gastrointestinal disorders, among others.

Claims

1. A method comprising

performing remote ischemic conditioning (RIC) on a limb of a subject having a condition that benefits from enhanced autophagy,

wherein RIC comprises two or more cycles of blood flow occlusion followed by reperfusion, wherein each cycle has a blood flow occlusion duration of one minute or more and wherein a second or subsequent cycle begins upon conclusion of reperfusion of a previous cycle, and

wherein the condition is Alzheimer'"'"'s disease, Parkinson'"'"'s disease or Huntington'"'"'s disease.

2. The method of claim 1, wherein the RIC is chronic RIC.

3. The method of claim 1, wherein the RIC is acute RIC.

4. The method of claim 1, wherein RIC is performed on a daily basis.

5. The method of claim 1, wherein RIC is performed more than once a day.

6. The method of claim 1, wherein RIC is performed on at least a daily basis for at least one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, or a year.

7. The method of claim 1, wherein RIC is performed every other day for at least one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, or a year.

8. The method of claim 1, wherein RIC comprises 3, 4, 5 or more cycles, each cycle comprising a blood occlusion period and a reperfusion period.

9. The method of claim 1, wherein each cycle comprising a 5 minute blood occlusion period and a 5 minute reperfusion period.

10. The method of claim 1, wherein the subject is receiving another therapy.

11. The method of claim 10, wherein the other therapy is administered at less than a maximum tolerable dose.

12. The method of claim 10, wherein the other therapy is administered at greater than the maximum tolerable dose.

13. The method of claim 1, wherein the condition is Alzheimer'"'"'s disease.

14. The method of claim 1, wherein the condition is Huntington'"'"'s disease.

15. The method of claim 1, wherein the condition is Parkinson'"'"'s disease.

16. The method of claim 1, wherein RIC is performed using a device comprising

a cuff configured to retract around the limb of the subject,

an actuator connected to the cuff that causes the cuff to contract about the limb to reduce blood flow there through, and

a controller that controls the actuator.

17. The method of claim 1, wherein the condition is not associated with ischemia/reperfusion injury.