Treatment for spinal muscular atrophy
AssigneeAcademia Sinica
InventorHung Li
Life of this patent
Estimating the term…
Abstract
Compositions for treatment of spinal muscular atrophy (SMA) and methods for use thereof to treat SMA and other conditions of SMN-deficiency; novel drug development targets for SMA therapies, and methods of use thereof to screen for candidate therapeutic and diagnostic agents.
Claims32
A method for treating spinal muscular atrophy (SMA) or other SMN-deficiency in a subject, the method comprising administering to said subject a therapeutically effective amount of a pharmaceutically acceptable activator of Stat5.
A method for treating SMA or other SMN-deficiency in a subject, the method comprising administering to said subject a recombinant genetic vector comprising at least one copy of a host-expressible gene encoding Stat5A.
A method for identifying a candidate compound for treatment of SMA comprising
- (A) providing (1) a mammalian cell that is Stat5(+) and that contains an expressible, Stat5-activatable target nucleic acid whose promoter contains at least one Gamma-Activated Sequence (GAS) element and at least one CTCNNNTAA motif, and (2) at least one test compound;
- (B) contacting the cell with the test compound (1) under conditions in which the test compound can activate Stat5 or (2) under conditions in which the test compound can increase expression of Stat5 and conditions in which Stat5 can be activated;
- and
- (C) detecting the level of expression of the target nucleic acid or of a phenotypic effect resulting from expression thereof,
- whereby detection of an increased level of expression of the target nucleic acid or an increase in the phenotypic effect identifies the test compound as a candidate compound for SMA treatment.
A nucleobase probe containing a base sequence of CTCNNNTAA or the complement thereof, or the RNA base equivalent to either of these.
A method for screening to identify a candidate Stat5-regulated gene, the method comprising:
- (A) providing a nucleobase probe containing a base sequence of CTCNNNTAA or the complement thereof, or the RNA base equivalent to either of these.
- (B) contacting a gene-containing cell, cell fragment, or polynucleotide preparation with the probe under conditions in which the probe can hybridize specifically to a sequence complementary to the base sequence of (A) to form hybrids, and removing non-specifically hybridized probes therefrom to leave remaining hybrids, and
- (C) detecting remaining hybrids and determining that the target sequence to which the base sequence of (A) has bound is located in a gene promoter region,
- whereby detection of a remaining hybrid identifies the gene member thereof, or the gene from which the promoter was obtained, as a candidate Stat5-regulated gene.
A method for screening to identify a candidate Stat5 protein comprising:
- (A) providing a nucleobase probe containing a base sequence of CTCNNNTAA or the complement thereof;
- (B) contacting the probe with a polypeptide having the amino acid sequence of Stat(5) or an amino acid sequence at least 70% identical thereto, under conditions in which the polypeptide can specifically bind to the base sequence of (A), to form a complex, and removing non-specifically bound probes therefrom to leave remaining complexes, and
- (C) detecting remaining complexes,
- whereby detection of a remaining complex identifies the polypeptide member thereof as a candidate Stat5 protein.
A method for treating SMA or other SMN-deficiency in a subject, the method comprising administering to said subject a recombinant genetic vector comprising at least one copy of a host-expressible gene encoding Stat5A and comprising at least one copy of a Stathmin inhibitor.
Dependencies are inferred from the claim text.