Clusterin for use in the treatment of thrombotic microangiopathies

Patent metadata

Field	Value
Publication number	US-12186366-B2
Application number	US-201816632684-A
Country	US
Kind code	B2
Filing date	Jul 20, 2018
Priority date	Jul 21, 2017
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The present invention concerns clusterin for use in the treatment of thrombotic microangiopathies, and a pharmaceutical composition comprising clusterin for use in the treatment of thrombotic microangiopathies, said composition not comprising von Willebrand factor protease. The present invention also concerns an ex vivo method for stratifying a patient suffering, or likely to be suffering, from TMA, comprising the following steps: 1) measuring, in a biological sample from said patient, the amount LC of clusterin, and 2) comparing the amount Lc measured in step 1) with an amount Lref of clusterin by calculating the score S1=LC/Lref, in which: •If S1≤1, the patient is considered to be likely to benefit from a treatment of the TMA with clusterin, •If S1>1, the patient is not considered to be likely to benefit from treatment of TMA with clusterin.

First claim

The invention claimed is:

1. A method of treating a thrombotic microangiopathy in a subject, comprising detecting a deficiency in serum clusterin level in said subject and treating the thrombotic microangiopathy by increasing serum clusterin levels in said subject by administering to the subject a therapeutically effective amount of a pharmaceutical composition wherein the composition consists of clusterin as an active agent, wherein the pharmaceutical composition excludes a von Willebrand factor-cleaving protease.

2. The method of claim 1 , wherein said clusterin is a human clusterin of sequence SEQ ID No.: 1.

3. The method of claim 1 , wherein said clusterin has a peptide sequence which has at least 90% identity with the sequence SEQ ID No.: 1.

4. The method of claim 1 , wherein said clusterin is a recombinant clusterin, a plasma clusterin, or a synthetic clusterin.

5. The method of claim 1 , wherein the thrombotic microangiopathy is thrombotic thrombocytopeniaurpura (TTP), hemolytic uremic syndrome (HUS) associated or not associated with bacteria, HELLP syndrome, or a secondary thrombotic microangiopathy.

6. The method of claim 1 , comprising oral or parenteral administration of said clusterin.

7. The method of claim 6 , wherein said parenteral administration is intravenous administration, intramuscular administration, or subcutaneous administration.

Assignees

• Univ Bordeaux
• Centre Nat Rech Scient
• Centre Hospitalier Univ Bordeaux
• Inserm—Institut National De La Sante Et De La Rech Medicale
• Univ Angers
• Centre Hospitalier Univ Dangers

Inventors

• Augusto Jean-Francois
• Contin-Bordes Cecile
• Delmas Yahsou
• Blanco Patrick
• Delneste Yves
• Jeannin Pascale
• Beauvillain Celine

Classifications

• G01N2800/226

  Thrombotic disorders, i.e. thrombo-embolism irrespective of location/organ involved, e.g. renal vein thrombosis, venous thrombosis · CPC title

• G01N33/92

  involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} · 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

• G01N2800/22

  Haematology · CPC title

• A61K38/1709 Primary

  from mammals · CPC title