Therapeutic or prophylactic composition for TDP-43 proteinopathy

Patent metadata

Field	Value
Publication number	US-2017226508-A1
Application number	US-201615370032-A
Country	US
Kind code	A1
Filing date	Dec 6, 2016
Priority date	Oct 7, 2015
Publication date	Aug 10, 2017
Grant date	—

Abstract

The present invention aims to provide a composition for the prevention or treatment of TDP-43 proteinopathy using a microRNA targeting the TDP-43 gene.
A prophylactic or therapeutic composition for TDP-43 proteinopathy, comprising: one or more nucleic adds selected from the group consisting of isolated RNAs and isolated nucleic acids encoding the RNAs, wherein the RNAs consist of human miR-33 represented by SEQ ID NO: 1, variants of the human miR-33 having one or more mutations, and precursors of the human miR-33 and the variants.

First claim

1 . A prophylactic or therapeutic composition for TDP-43 proteinopathy, comprising:
one or more nucleic acids selected from the group consisting of isolated RNAs of human miR-33 represented by SEQ ID NO: 1, isolated RNAs of variants of the human miR-33, isolated RNAs of precursors thereof, and isolated nucleic acids encoding the RNAs.

2 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , wherein the mutation site is a base at position 1, or one or more bases at or subsequent to position 9 from the 5′ end of the human miR-33.

3 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , wherein the mutation is a substitution, a deletion, or an insertion of 5 or less bases.

4 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , wherein the precursors are double-stranded miRNAs and/or pre-miRNAs.

5 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , to wherein the isolated nucleic acids encoding the RNAs are functionally encoded by a virus vector.

6 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 5 , wherein the virus vector is a lentivirus vector or an adeno-associated virus vector.

7 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , wherein the RNA comprises at least one or more modified nucleotides.

8 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , wherein the one or more nucleic acids are encapsulated in nanoparticles.

9 . The prophylactic or therapeutic composition for TDP-43 proteinopathy according to claim 1 , wherein the TDP-43 proteinopathy is SOD1-unrelated amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin inclusions.

Assignees

• Univ Kyoto

Inventors

• Inoue Haruhisa
• Tsuge Itaru
• Ono Koh
• Suzuki Shigehiko
• Naitoh Motoko

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P21/02

  Muscle relaxants, e.g. for tetanus or cramps · CPC title

• C12N2310/20

  involving clustered regularly interspaced short palindromic repeats [CRISPR] · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C12N15/113 Primary

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title