STAUFEN1 agents and associated methods
Methods of minimizing dysregulation of Staufen1-associated RNA metabolism can include introducing an amount of a Staufen1-regulating agent to a target cell sufficient to minimize the dysregulation. Therapeutic compositions for treating a neurodegenerative condition associated with Staufen1-induced dysregulation of RNA metabolism can include a therapeutically effective amount of a Staufen1-regulating agent and a pharmaceutically acceptable carrier.
1. A therapeutic composition for treating a neurodegenerative condition associated with Staufen1-induced dysregulation of RNA metabolism, comprising:
a therapeutically effective amount of a Staufen1-regulating agent including an antisense oligonucleotide (ASO) having a nucleotide sequence that is at least 85% homologous to and having the same number of nucleotides as SEQ ID NO: 1, SEQ ID NO: 2, or a combination thereof; and
a pharmaceutically acceptable carrier;
wherein the therapeutic composition when administered in a therapeutically effective amount is operable to reduce Staufen1 expression, reduce Staufen1 activity, reduce mutant ATXN2 expression, reduce mTOR expression, reduce or block Staufen1 interaction with mRNAs resulting in altered mRNA expression or abundance, or a combination thereof.
2. The composition of claim 1 , wherein the Staufen1-regulating agent comprises a nucleotide sequence that is at least 85% homologous to SEQ ID NO: 1.
3. The composition of claim 1 , wherein the Staufen 1-regulating agent is present in the therapeutic composition at a concentration of from about 1 picomolar (pM) to about 100 millimolar (mM).
4. The composition of claim 1 , wherein the Staufen1-regulating agent is present in the therapeutic composition at a concentration of from about 0.001 μg/g to about 200 mg/g.
5. The composition of claim 1 , further comprising a delivery vector to facilitate delivery of the Staufen1-regulating agent into a target cell.
6. The composition of claim 5 , wherein the delivery vector is a viral vector.
7. The composition of claim 6 , wherein the viral vector is a member of the group consisting of: a retrovirus, a lentivirus, a cytomegalovirus, an adenovirus, an adeno-associated virus, and combinations thereof.
8. The composition of claim 5 , wherein the delivery vector is a non-viral carrier selected from the group consisting of: an aptamer, an antibody, an antibody fragment, a polypeptide, N-acetylgalactosamine, a vitamin, a small organic molecule, a polycationic peptide, a polymer, a dendrimer, a lipid, a lysosomal carrier, a liposome, a micelle, a quantum dot, a nanoparticle, and combinations thereof.
9. The composition of claim 1 , wherein the pharmaceutically acceptable carrier is formulated for administration via injection, enteral administration, transdermal administration, transmucosal administration, inhalation, or implantation.
10. The composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises water, a solubilizing agent, a tonicity agent, a pH adjuster, a buffering agent, a preservative, a chelating agent, a bulking agent, a binder, a disintegrant, a filler, a thickener, a dispersant, an emulsifier, an emollient, or combinations thereof.
11. The composition of claim 1 , further comprising a supplementary therapeutic agent.
12. The composition of claim 11 , wherein the supplementary therapeutic agent is a member selected from the group consisting of: a dopaminergic agent, a cholinesterase inhibitor, an antipsychotic agent, an analgesic, an anti-inflammatory agent, an inducer of autophagy, and combinations thereof.