Nurr1 as a genetic target for treating levodopa-induced dyskinesias in Parkinson's disease
Methods of treating movement disorders by reducing the activity of Nurr1 are disclosed. These methods are particularly applicable to subjects suffering from Parkinson's disease who have either developed levodopa-induced dyskinesia (LID) or are at risk of developing LID. In some aspects, the invention relates to a method for treating a movement disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition, wherein said composition reduces the activity of a nuclea receptor related 1 protein (“Nurr1”). In some embodiments, the movement disorder is a dyskinesia. The movement disorder may be a levodopa-induced dyskinesia.
1. A method for treating dyskinesia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition, wherein said composition comprises a nucleic acid molecule that encodes an antisense molecule, a small interfering RNA molecule (siRNA), a short hairpin RNA molecule (shRNA), or a microRNA molecule (miRNA) that targets a nuclear receptor related 1 protein (“Nurr1”) and reduces the activity of said Nurr1 to thereby treat dyskinesia.
2. The method of claim 1 , wherein said shRNA targets Nurr1 mRNA for degradation.
3. The method of claim 1 , wherein the composition comprises a virus.
4. The method of claim 3 , wherein the virus is an adeno-associated virus (“AAV”), adenovirus, herpes simplex virus, or lentivirus.
5. The method of claim 4 , wherein the virus is AAV.
6. The method of claim 5 , wherein the virus is AAV1.
7. The method of claim 3 , wherein a genome of said virus comprises said nucleic acid molecule.
8. The method of claim 1 , wherein administering comprises inserting the composition at a desired location.
9. The method of claim 8 , wherein the desired location is the brain.
10. The method of claim 9 , wherein the desired location is the striatum.
11. The method of claim 10 , wherein the desired location is the denervated striatum.
12. The method of claim 8 , wherein inserting comprises injecting the composition.
13. The method of claim 1 , wherein the subject is a mammal.
14. The method of claim 1 , wherein the subject is a primate, porcine, canine, ovine, or rodent.
15. The method of 1 , wherein the subject is a human.
16. A method for treating levodopa-induced dyskinesia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition, wherein:
the composition comprises a nucleic acid molecule that encodes an antisense molecule, a small interfering RNA molecule (siRNA), a short hairpin RNA molecule (shRNA), or a microRNA molecule (miRNA) that targets a nuclear receptor related 1 protein (“Nunn1”);
administering comprises inserting the composition into the brain; and
the composition reduces the activity of said Nurr1 to thereby treat levodopa-induced dyskinesia.