Inhibitors of cacna1a/alpha1a subunit internal ribosomal entry site (ires) and methods of treating spinocerebellar ataxia type 6
AssigneeThe University of Chicago
InventorsChristopher M. Gomez, Xiaofei Du
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Abstract
The disclosure provides methods of treating polyglutamine diseases, e.g., spinocerebellar ataxia Type 6, in a subject, comprising administering to the subject an IRES inhibitor in an amount effective for treating the SCA6 in the subject. Also provided herein are the IRES inhibitors, and pharmaceutical compositions comprising the same.
Claims42
A method of treating spinocerebellar ataxia Type 6 (SCA6) in a subject in need thereof, comprising the step of administering to the subject an IRES inhibitor in an amount effective for treating the SCA6 in the subject.
A method of treating a subject with a predisposition to spinocerebellar ataxia Type 6 (SCA6), comprising the step of administering to the subject an IRES inhibitor in an amount effective for delaying development of SCA6 in the subject.
The method of any one of the preceding claims, wherein the IRES inhibitor is an antisense molecule.
The method of any one of the preceding claims, wherein the IRES inhibitor blocks binding of the IRES of the α1A mRNA to an IRES Trans-Acting Factor.
An antisense molecule comprising at least 15 contiguous nucleobases of SEQ ID NO:
- 9, SEQ ID NO:
- 10, or SEQ ID NO:
- 11.
An antisense molecule comprising at least 15 contiguous nucleobases of a sequence that (i) differs from SEQ ID NO:
- 9 by not more than 3 nucleobases or (ii) is at least 90% identical to the sequence set forth in SEQ ID NO:
- 9.
An antisense molecule comprising at least 15 contiguous nucleobases of a sequence that (i) differs from SEQ ID NO:
- 10 by not more than 3 nucleobases or (ii) is at least 90% identical to the sequence set forth in SEQ ID NO:
- 10.
An antisense molecule comprising at least 15 contiguous nucleobases of a sequence that (i) differs from SEQ ID NO:
- 11 by not more than 3 nucleobases or (ii) is at least 90% identical to the sequence set forth in SEQ ID NO:
- 11.
A method of identifying a compound with SCA6 therapeutic activity, comprising the steps of (i) contacting the compound with a sample comprising a nucleic acid molecule comprising at least a portion of the α1A mRNA, wherein the portion comprises at least the nucleotide sequence of the IRES of the α1A mRNA and the coding sequence of α1ACT, and (ii) assaying for expression of α1ACT, wherein the compound is identified as a compound with anti-SCA6 therapeutic activity when expression of α1ACT mRNA is reduced compared to a control.
Dependencies are inferred from the claim text.