Method of treating heterotopic ossification

Patent metadata

Field	Value
Publication number	US-10953028-B2
Application number	US-201916397029-A
Country	US
Kind code	B2
Filing date	Apr 29, 2019
Priority date	Dec 24, 2015
Publication date	Mar 23, 2021
Grant date	Mar 23, 2021

Abstract

The invention provides a method of treating heterotopic ossification in a subject in need thereof. The method comprises administering a hypoxia inducible factor-1α (Hif-1α) inhibitor to the subject. In various embodiments, the Hif-1α inhibitor is PX-478, rapamycin, or digoxin.

First claim

What is claimed:

1. A method of inhibiting the development of intramuscular heterotopic ossification (HO) in a subject that has suffered from a burn, the method comprising administering to rapamycin or PX-478 a subject with a >20% total body surface area (TBSA) burn to inhibit the development of intramuscular HO.

2. The method of claim 1 , wherein the >20% TBSA burn is a >30% TBSA burn.

3. The method of claim 1 , comprising administering the rapamycin to the subject by injection.

4. The method of claim 1 , comprising systemically administering the PX-478 to the subject by injection.

5. The method of claim 1 , wherein the administering step leads to a complete absence of intramuscular HO in the subject.

6. The method of claim 1 , wherein the-subject has (i) suffered from a musculoskeletal trauma, (ii) undergone surgical resection of an HO, or (iii) a non-resectable HO.

7. A method of inhibiting the development of intramuscular ectopic bone formation in a subject who has undergone a hip replacement or a joint arthroplasty or has suffered from a spinal cord injury, the method comprising administering rapamycin or PX-478 to a subject who has undergone a hip replacement or a joint arthroplasty or has suffered from a spinal cord injury rapamycin to inhibit the development of intramuscular ectopic bone formation.

8. The method of claim 7 , wherein the administering step leads to a complete absence of intramuscular ectopic bone formation in the subject.

9. The method of claim 7 , wherein upon administering the rapamycin to the subject, intramuscular ectopic bone formation is not evident in the subject.

10. The method of claim 7 , wherein the administering step leads to decreased cartilage formation and/or formation or a mesenchymal condensation in the subject.

11. The method of claim 7 , comprising administering the rapamycin to the subject by injection.

12. The method of claim 7 , comprising systemically administering the PX-478 to the subject by injection.

13. The method of claim 7 , wherein the method has no adverse effects on wound healing in the subject.

Assignees

• Univ Michigan Regents

Inventors

• Levi Benjamin
• Agarwal Shailesh

Classifications

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61K31/436

  the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin · CPC title

• A61K31/7048 Primary

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61K31/198

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title