IP Library Granted Patent US 12,280,064
Granted Patent B2
US 12,280,064 · App. 18/297,285 · Granted Apr 22, 2025

Calmodulin inhibitors for the treatment of ribosomal disorders and ribosomopathies

Inventors: Leonard I. Zon (Wellesley, MA); Alison M. Taylor (Cambridge, MA)
A61K31/553A61K31/145A61K31/4184A61K31/4375A61K31/4418A61K31/495A61K31/4965A61K31/54A61K31/5415
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Quick Facts
Patent No.
US 12,280,064
App. No.
18/297,285
Granted
Apr 22, 2025
Kind
B2
Abstract

The present invention relates generally to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathy, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to methods for the use of calmodulin inhibitors and calcium channel blockers for treatment of ribosomal disorders and ribosomopathy, e.g. Diamond Blackfan anemia (DBA).

Claims (9)

1. A method of treating a subject with Diamond Blackfan Anemia (DBA), comprising administering an effective amount of a calmodulin inhibitor to the subject to decrease p53 or p21 in at least one of CD34+ cells, erythroid cells or erythroid differentiated cells in the subject, wherein the calmodulin inhibitor is N-(6-aminohexyl)-5-bromo-2-naphthalenesulfonamide.

2. The method of claim 1 , wherein the subject has DBA1, DBA2, DBA3, DBA4, DBA5, DBA6, DBA7, or DBA8.

3. The method of claim 1 , wherein the subject has a mutation in ribosomal protein 19 (RPS19).

4. The method of claim 1 , wherein the subject has a mutation in ribosomal protein selected from RPS7, RPS10, RPS19, RPS24, PRS26, RPS17, PRS27L, RPS29, RPL35A, PRL5 and PPL11.

5. The method of claim 1 , wherein the subject has a mutation in a ribosomal protein selected from: rPL2A, rPL2B, rPL3, rpL4A, rPL4B, rPL7A, rPL7B, rPL10, rPL11, rPL16A, rPL17A, rPL17B, rPL18A, rPL18B, Rp119A, rPL19, rPL25, rPL29, rpL31A, rpL31B, rPL36A, rPL40A, rPS1A, rPS6A, rPS6B, rPS14A, rPS15, rPS19, rPS23B, rPS25A, rPS26B, rPS29, rPS29B and rPS31.

6. The method of claim 1 , wherein the subject is administered another therapeutic agent to treat the ribosomal protein defect, selected from the group consisting of: corticosteroids and blood transfusions.

7. The method of claim 1 , wherein the calmodulin inhibitor increases the number of CD71+ erythroid cells in the subject.

8. The method of claim 1 , wherein the calmodulin inhibitor increases hemoglobin levels in the subject.

9. The method of claim 1 , wherein the subject has a symptom of macrocytic anemia or craniofacial abnormalities.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 10, 2025
From: ZON, LEONARD I.; TAYLOR, ALISON M.
To: CHILDREN'S MEDICAL CENTER CORPORATION
Reel/Frame 069810/0586 →
Continuity (7)
Continuation 17353717 · Jun 21, 2021
Continuation 16538293 · Aug 12, 2019
Continuation 15806765 · Nov 8, 2017
Continuation 14385524
Provisional Application 61611751 · Mar 16, 2012
Provisional Application 61611845 · Mar 16, 2012
Related Publication 20240091238A1 · Mar 21, 2024
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Cited By (1)
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