Treatment of aging-associated conditions by DNA degradation

Patent metadata

Field	Value
Publication number	US-11766446-B2
Application number	US-201917279280-A
Country	US
Kind code	B2
Filing date	Sep 25, 2019
Priority date	Sep 25, 2018
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

Abstract

Provided herein, in some embodiments, are methods for treating age-associated conditions, including systemic inflammation and disease, via enhanced DNA degradation.

First claim

The invention claimed is:

1. A method for treating an aging-associated condition in a subject, comprising:
administering a DNase enzyme to the subject,
wherein the aging-associated condition is a laminopathy, an interferonopathy, ataxia telangiectasia (A-T), Hutchison-Gilford progeria, or aging-associated inflammation and cellular senescence that is induced or enhanced by treatment with a chemotherapeutic agent.

2. The method of claim 1 , wherein the DNase enzyme is administered by systemic or local administration.

3. The method of claim 1 , wherein the DNase enzyme is administered by gene therapy.

4. The method of claim 1 , wherein the DNase enzyme is a lysosomal nuclease enzyme.

5. The method of claim 1 , wherein the DNase enzyme is DNASE2A or a derivative of DNASE2A.

6. The method of claim 5 , wherein the derivative of DNASE2A is functionally enhanced relative to DNASE2A.

7. The method of claim 1 , wherein said chemotherapeutic agent is a DNA damaging agent, optionally cytarabine (ara-C).

8. The method of claim 1 , wherein the subject is identified as having elevated levels of extranuclear DNA and/or SA-β-gal activity relative to a control.

9. The method of claim 1 , wherein the subject is identified as having elevated levels of:
(i) one or more autophagy genes, optionally ATG5, BECLIN1, P62, or PTEN;
(ii) one or more autophagosome marker, optionally LC3;
(iii) one or more lysosomal protein, optionally LAMP1; and/or
(iv) one or more inflammatory genes, optionally MX1, CXCL10, or IL-6 relative to a control.

10. A method for treating an aging-associated condition in a subject, comprising:
identifying a subject as having elevated levels of extranuclear DNA relative to a control; and
administering a DNase enzyme to the subject.

11. A method for treating an aging-associated condition in a subject, comprising:
identifying a subject as having elevated levels of SA-β-gal activity relative to a control; and
administering a DNase enzyme to the subject.

12. The method of claim 8 , wherein the control is a sample from a subject who does not have an aging-associated condition.

13. The method of claim 8 , wherein the control is a predetermined value.

14. The method of claim 1 , wherein the subject is a human.

Assignees

• Massachusetts Gen Hospital

Inventors

• Lan Yuk Yuen
• Hacohen Nir

Classifications

• A61K31/7068 Primary

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• C12N9/22 Primary

  Ribonucleases {[RNase]; Deoxyribonucleases [DNase]} · CPC title

• A61K38/465

  acting on ester bonds (3.1), e.g. lipases, ribonucleases · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C12Y301/22001

  Deoxyribonuclease II (3.1.22.1) · CPC title