EP-4734990-A1 - USES OF IRON CHELATORS FOR TREATING STUTTERING

Abstract

Provided herein are uses of iron chelators to treat stuttering. The iron chelators include deferiprone, deferoxamine, and deferasirox.

Inventors

• SHEIKHBAHAEI, Shahriar

Assignees

• The United States of America, as Represented By the Secretary, Department of Health and Human Services

Dates

Publication Date

20260506

Application Date

20240628

Claims (20)

1. 1. A method of treating a stutter in a subject in need thereof, comprising administering to the subject a composition comprising an iron chelator.
2. 2. The method of claim 1, wherein the composition comprises a pharmaceutically acceptable excipient.
3. 3. The method of claim 1, wherein the iron chelator is selected from the group consisting of deferiprone; deferoxamine; deferasirox; lactoferrin; ethylenediaminetetraacetic acid (EDTA); diethylenetriaminepentaacetic acid (DTP A); a siderophore; N-hydroxyalkyl-substituted deferiprone; deferoxamine conjugated to polyethylene glycol)poly(aspartic acid) block copolymers; deferoxamine conjugated to hydroxyethyl starch; deferitrin; CN128; and PBT434.
4. 4. The method of claim 3, wherein the iron chelator is deferiprone.
5. 5. The method of claim 4, wherein the deferiprone is administered orally.
6. 6. The method of claim 5, wherein the deferiprone is administered at a dose of about 20-100 mg/kg daily.
7. 7. The method of claim 3, wherein the iron chelator is deferoxamine.
8. 8. The method of claim 7, wherein the deferoxamine is administered parenterally.
9. 9. The method of claim 8, wherein the deferoxamine is administered subcutaneously or intravenously.
10. 10. The method of claim 9, wherein the deferoxamine is administered at a dose of about 20-60 mg/kg daily.
11. 11. The method of claim 3, wherein the iron chelator is deferasirox.
12. 12. The method of claim 11, wherein the deferasirox is administered orally.
13. 13. The method of claim 12, wherein the deferasirox is administered at a dose of about 20-30 mg/kg daily.
14. 14. A method of treating a stutter in a subject in need thereof comprising orally administering to the subject a composition comprising deferiprone and a pharmaceutically acceptable excipient.
15. 15. The method of claim 14, wherein the deferiprone is administered at a dose of about 20-100 mg/kg daily.
16. 16. The method of claim 15, wherein the deferiprone is administered at dose of about 25-33 mg/kg three times daily.
17. 17. A composition comprising an iron chelator for treating a stutter.
18. 18. The composition of claim 17, wherein the composition comprises a pharmaceutically acceptable excipient.
19. 19. The composition of claim 17, wherein the iron chelator is selected from the group consisting of deferiprone; deferoxamine; deferasirox; lactoferrin; ethylenediaminetetraacetic acid (EDTA); diethylenetriaminepentaacetic acid (DTP A); a siderophore; N-hydroxyalkyl-substituted deferiprone; deferoxamine conjugated to polyethylene glycol)poly(aspartic acid) block copolymers; deferoxamine conjugated to hydroxyethyl starch; deferitrin; CN128; and PBT434.
20. 20. The composition of claim 19, wherein the iron chelator is deferiprone.

Description

USES OF IRON CHELATORS FOR TREATING STUTTERING STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0001] This invention was made in part with Government support under NIH ZIA NS009420. The Government has certain rights in this invention. FIELD OF THE INVENTION [0002] The present invention relates to the use of iron chelators to treat stuttering. The iron chelators include deferiprone, deferoxamine, and deferasirox. BACKGROUND OF THE INVENTION [0003] The American Psychiatric Association (APA) defines childhood-onset fluency disorder (also known as stuttering) as a persistent disruption in the normal fluency and time pattern of speech that is not appropriate for the individual’s age. Stuttering is the most frequent type of speech disorder and is considered a neurodevel opmental motor disorder. People who stutter may struggle with a lower quality of life, face educational and occupation barriers, and be denied access to quality treatment plans. Although stuttering affects about 1% of the adult U.S. population, it is estimated that approximately 10% of the population at some point in their life are challenged by speech disorders. Stuttering is present in all cultural, racial, ethnic, and economic groups studied. It is a highly inheritable disorder, as genetic factors contribute to more than 80% of cases. While stuttering has been known for centuries, its etiology is not fully understood, and no treatment has yet to be approved by the Food and Drug Administration (or other federal government agencies) to improve the quality of life in people who stutter. Accordingly, there is a need in the art for therapeutics to treat stuttering. SUMMARY OF THE INVENTION [0004] Provided herein is a method of treating a stutter in a subject in need thereof. The method may comprise administering to the subject a composition comprising an iron chelator. Also provided herein are use of the composition in the manufacture of a medicament for treating a stutter and the composition for treating a stutter. The composition may comprise a pharmaceutically acceptable excipient. The iron chelator may comprise one or more of deferiprone; deferoxamine; deferasirox; lactoferrin; ethylenediaminetetraacetic acid (EDTA); diethylenetriaminepentaacetic acid (DTP A); a siderophore; N-hydroxyalkyl-substituted deferiprone; deferoxamine conjugated to poly(ethylene glycol)poly(aspartic acid) block copolymers; deferoxamine conjugated to hydroxyethyl starch; deferitrin; CN128; and PBT434. [0005] The iron chelator may comprise deferiprone. The deferiprone may be administered or intended to be administered orally. The deferiprone may be administered or intended to be administered at a dose of about 20-100 mg/kg daily. [0006] The iron chelator may comprise deferoxamine. The deferoxamine may be administered or intended to be administered parentally. The parental administration may be subcutaneous or intravenous. The deferoxamine may be administered or intended to be administered at a dose of about 20-60 mg/kg daily. [0007] The iron chelator may comprise deferasirox. The deferasirox may be administered or intended to be administered orally. The deferasirox may be administered or intended to be administered at a dose of about 20-30 mg/kg daily. [0008] Provided herein is a method of treating a stutter in a subject in need thereof, which may comprise orally administering to the subject a composition comprising deferiprone and a pharmaceutically excipient. Also provided are use of the composition in the manufacture of a medicament for treating a stutter and the composition for use in treating a stutter. The medicament or composition may be intended for oral administration. The deferiprone may be administered or intended to be administered at a dose of about 2-100 mg/kg daily, or a dose of about 25-33 mg/kg three times daily. BRIEF DESCRIPTION OF THE DRAWINGS [0009] FIGS. 1A-E show that iron is accumulated in Gnptab-mutant mice. FIG. 1A. A brain of a wild-type mouse. FIG. IB shows iron accumulation of a Gnptab-mutant mouse. FIGS. 1C-1E shows statistically significant accumulation of iron in the mediolateral striatum (FIG. 1C), central striatum (FIG. ID), and dorsolateral striatum (FIG. IE) of Gnptab-mutant mice as compared to controls. [0010] FIGS. 2A-D show that deferiprone (DFP) treatment improved deficits of vocal and grooming behaviors in Gnptab-mutant male mice. FIG. 2A shows the study schematic. FIGs. 2B- C show that iron content decreases in the brains of Gnptap-mutant mice after DFP treatment (FIG. 2C) as compared to before treatment (FIG. 2B). FIG. 2D shows quantification of compound vocalization in wild-type and Gnptab-mutant mice treated with DFP. [0011] FIGS. 3 A-B show that administering DFP to Gnptab-mutant mice for 30 days improves vocal deficits. FIG. 3A shows the experimental scheme. FIG. 3B shows the results as measured by compound vocalization. [0012] FIGS. 4A-B show that administering DFP to Gnptab-mutant mice for 60 days improv