Methods of treating fragile X syndrome and related disorders
Disclosed herein are novel methodologies of treating fragile X syndrome and related disorders by inhibiting mGlu 5 -relevant signaling pathways via the reduction of β-arrestin2 protein levels or the diminution of mGlu 5 and β-arrestin2 protein interactions.
1. A method of treating fragile X syndrome, fragile X-associated tremor/ataxia syndrome, an autism spectrum disorder, or tuberous sclerosis, comprising administering to a subject in need thereof an effective amount of a compound that reduces β-arrestin2 protein levels in said subject.
2. The method of claim 1 , wherein the reduction of β-arrestin2 protein levels ameliorates increased protein synthesis, altered synaptic plasticity, or behavioral impairments in the fragile X syndrome, fragile X-associated tremor/ataxia syndrome, an autism spectrum disorder, or tuberous sclerosis.
3. The method of claim 1 , wherein the subject in need thereof suffers from fragile X syndrome.
4. The method of claim 1 , wherein the compound knocks out or disrupts the β-arrestin2 gene.
5. The method of claim 4 , wherein the compound comprises a zinc finger nuclease, a transcription activator-like effector nuclease (TALEN), a meganuclease, or a CRISPR/Cas9 system.
6. The method of claim 1 , wherein the compound comprises a molecule that alters β-arrestin2 mRNA splicing, stability, or translation.
7. The method of claim 6 , wherein the compound comprises an inhibitory nucleic acid molecule.
8. The method of claim 7 , wherein the inhibitory nucleic acid molecule is an antisense nucleic acid, a locked nucleic acid molecule, a peptide nucleic acid molecule, a morpholino, a siRNA molecule, a shRNA molecule or a ribozyme.
9. The method of claim 1 , wherein the compound is administered periodically.