Messenger RNA therapy for the treatment of Friedreich's ataxia

Patent metadata

Field	Value
Publication number	US-10780183-B2
Application number	US-201816012138-A
Country	US
Kind code	B2
Filing date	Jun 19, 2018
Priority date	Jun 19, 2017
Publication date	Sep 22, 2020
Grant date	Sep 22, 2020

Abstract

The present invention provides methods and compositions of treating Friedreich's ataxia (FRDA) based on administering an mRNA encoding a frataxin protein.

First claim

We claim:

1. A method of treating Friedreich's ataxia (FRDA), comprising
administering to a subject in need of treatment a composition comprising an mRNA encoding a frataxin protein, wherein the composition is administered via intrathecal (IT) delivery, wherein the mRNA comprises sequence identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, and wherein the administering of the composition results in expression of the frataxin protein detectable in the cerebellum of the subject.

2. The method of claim 1 , wherein the administering of the composition results in expression of the frataxin protein detectable in the liver, the spinal cord, the brain, and/or at least one dorsal root ganglion (DRG) of the subject.

3. The method of claim 1 , wherein the mRNA is encapsulated within a liposome.

4. The method of claim 3 , wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids.

5. The method of claim 4 , wherein the one or more cationic lipids comprise a cationic lipid selected from the group consisting of C12-200, MC3, DLinDMA, DLinkC2DMA, cKK-E12, ICE (Imidazole-based), HGT5000, HGT5001 (CCBene), OF-02, DODAC, DDAB, DMRIE, DOSPA, DOGS, DODAP, DODMA and DMDMA, DODAC, DLenDMA, DMRIE, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, DLinDAP, DLincarbDAP, DLinCDAP, DLin-K-DMA, DLin-K-XTC 2 -DMA, HGT 4003 , and combinations thereof.

6. The method of claim 4 , wherein the liposome further comprises a sphingomyelin.

7. The method of claim 1 , wherein the mRNA is administered once a week, once a month, twice a month, or once every 14 days.

8. A method of delivering frataxin in vivo, comprising administering periodically to a subject with Friedreich's ataxia (FRDA) a composition comprising an mRNA encoding a frataxin protein wherein that the frataxin protein is expressed in vivo at a level of at least 10% of a normal control level in cerebellum of the subject, wherein the composition is administered to via intrathecal (IT) delivery, and wherein the mRNA comprises sequence identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

9. The method of claim 8 , wherein the frataxin protein is expressed in the liver, the spinal cord, the brain, and/or at least one dorsal root ganglion (DRG) of the subject.

10. The method of claim 8 , wherein the mRNA is administered once a week, once a month, twice a month, or once every 14 days.

Assignees

• Translate Bio Inc

Inventors

• Heartlein Michael
• Derosa Frank
• Cherry Jonathan
• Lewis Paula
• Karve Shrirang
• Patel Zarna
• Parekh Darshan
• Wood Susan
• Chiu Chi-Sung
• Woo Caroline J

Classifications

• C12N15/62 Primary

  DNA sequences coding for fusion proteins · CPC title

• A61K9/0087

  Galenical forms not covered by A61K9/02 - A61K9/7023 · CPC title

• C12N15/88

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title