Treatment of nervous system disorders using combinations of RXR agonists and thyroid hormones

1. A method of treating Parkinson's disease, the method comprising administering to an individual in need thereof a therapeutically effective amount of a RXR agonist and a thyroid hormone, wherein administration of the combination of the RXR agonist and the thyroid hormone treats the Parkinson's disease in the individual, wherein the RXR agonist is 3,7-dimethyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid, and has the structure of formula III:

and wherein the combination of RXR agonist and thyroid hormone causes a greater improvement in the Parkinson's disease than the RXR agonist or thyroid hormone alone;

the method further comprising administration of a neurotrophic factor.

2. The method of claim 1 , wherein the neurotrophic factor is brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), fibroblast growth factor, basic (bFGF), ciliary neurotrophic factor (CNTF), neurotrophic factors-4/5 (NT-4/5), insulin-like growth factor (IGF), or insulin.

3. The method of claim 1 , wherein the neurotrophic factor is brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), fibroblast growth factor, basic (bFGF), insulin-like growth factor (IGF), or insulin.

4. The method of claim 1 , wherein the neurotrophic factor is GDNF.

5. The method according to claim 1 , wherein the combination of RXR agonist and thyroid hormone treats the nervous system disorder in the individual both by 1) promoting remyelination or neuroprotection of neurons and 2) modulating the individual's immune system.

6. The method according to claim 1 , wherein the further administration of the neurotrophic factor promotes remyelination or neuroprotection.

7. The method according to claim 1 , wherein the therapeutically effective amount of the RXR agonist is about 0.001 mg/day to about 20 mg/day.

8. The method according to claim 1 , wherein the therapeutically effective amount of the RXR agonist is about 1 mg/day to about 10 mg/day.

9. The method according to claim 1 , wherein the thyroid hormone is thyroxine.

10. The method according to claim 9 , wherein the dose of thyroxine is about 12.5 μg/day to about 250 μg/day.

11. The method according to claim 1 , wherein the RXR agonist is administered directly to the central nervous system.

12. The method according to claim 1 , wherein the combination of RXR agonist and thyroid hormone is administered directly to the central nervous system.

13. The method according to claim 1 , wherein the combination of RXR agonist, thyroid hormone, and neurotrophic factor is administered directly to the central nervous system.

14. The method according to claim 1 , wherein the neurotrophic factor is administered directly to the central nervous system.

15. The method according to claim 1 , wherein the thyroid hormone is administered directly to the central nervous system.

16. The method according to claim 1 , wherein the RXR agonist is administered by nasal administration.

17. The method according to claim 1 , wherein the thyroid hormone is administered by nasal administration.

18. The method according to claim 1 , wherein the neurotrophic factor is administered by nasal administration.

19. The method according to claim 1 , wherein the combination of RXR agonist, thyroid hormone is administered by nasal administration.

20. The method according to claim 19 , wherein the neurotrophic factor is administered by nasal administration.

21. The method according to claim 1 , wherein the thyroid hormone is administered orally or subcutaneously.

22. The method according to claim 1 , wherein the RXR agonist is administered orally or subcutaneously.

23. The method according to claim 1 , wherein the neurotrophic factor is administered subcutaneously or intramuscularly.

24. The method according to claim 1 , wherein the neurotrophic factor is insulin.

25. The method according to claim 1 , wherein the neurotrophic factor is IGF.

26. The method according to claim 1 , wherein the neurotrophic factor is NGF.

27. The method according to claim 1 , wherein the neurotrophic factor is BDNF.

28. The method according to claim 1 , wherein treatment with the combination of RXR agonist and thyroid hormone reduces at least one symptom of Parkinson's disease, wherein the at least one symptom reduced is tremor in the hands, tremor in the limbs, postural tremor, stiff muscles, difficulty standing, difficulty walking, difficulty with bodily movements, involuntary movements, muscle rigidity, problems with coordination, rhythmic muscle contractions, slow bodily movement, slow shuffling gait, daytime sleepiness, early awakening, nightmares, restless sleep, fatigue, dizziness, poor balance, restlessness, amnesia, confusion in the evening hours, dementia, difficulty thinking and understanding, impaired voice, soft speech, voice box spasms, anxiety, apathy, distorted sense of smell, loss of smell, dribbling of urine, leaking of urine, jaw stiffness, reduced facial expression, blank stare, constipation, depression, difficulty swallowing, drooling, falling, fear of falling, loss in contrast sensitivity, neck tightness, small handwriting, trembling, or unintentional writhing.