NeuroEPO in patients with Parkinson disease stage II-III

INTERVENTION: Erythropoietin Group A (experimental): 0.5 mg NeuroEPO by intranasal route, 3 times a week for 4 weeks (induction period) and, then continue with 1mg weekly for 20 weeks (maintenance period). Group B (experimental): 1.0 mg NeuroEPO by intranasal route, 3 times a week for 4 weeks (induction period) and then, continue with the same doses weekly for 20 weeks (maintenance period). Group C (control): Placebo. This group will be divide in two equal subgroups (one for each experimental group). The patients will receive the same doses, schema and administration route. NeuroEPO CONDITION: Parkinson Diseases Parkinson's disease stage II‐III PRIMARY OUTCOME: Total UPDRS Value (UPDRS scale). Measuring time: 9 months. INCLUSION CRITERIA: 1. Patients with Parkinson's disease, who meet the diagnostic criteria of BBL and stage II‐III according to Hoehn and Yahr scale. 2. Patients older than 18 years. 3. One or more years of evolution of motor symptoms. 4. Good response to dopaminergic stimulation. 5. Acceptable general health status, not previous polygllobulia (Hto equal or lower than 50). 6. Patients who consent to participate in the study by signing the informed consent model. SECONDARY OUTCOME: Related to eficacy 1. UPDRS motor. measure by UPDRS III. Measuring time: 0, 6, 9 months 2. Daytime mobility fluctuations: measured by self‐report. Measure by: Presence of on/off (on and off) dyskinesias (yes/no), dystonias (score), paradoxical fluctuations (score). Measuring time: 0, 6, 9 months 3. Total dose of dopaminergic stimulation. Measure by percentage. Measuring time: in each administration of the product. 4. Cognitive impairment. Measured by the DRS (Dementia Rating Scale) by Mattis. Measuring time:: 0, 9 months 5. Mental flexibility. Measured by the Trail Test (TMT). Measuring time: 0, 9 months 6. Working Memory. Measured by the TMT. Measuring time: 0, 9 months 7. Motor response rate. Measured by the TMT. Measuring time: 0, 9 months 8. Sustained attention. Measured by subtest 2 of the WAIS III Working Memory Index. Measuring time: 0, 9 months 9. Working memory. Measured by subtest 2 of the WAIS III Working Memory Index. Measuring time: 0, 9 months 10. Phonological verbal fluency. Measured by the Verbal Fluency Test (FAST). Measuring time: 0, 9 months 11. Semantic verbal fluency. Measured by FAST. Measuring time: 0, 9 months 12. Ability to alternate mental categories. Measured by FAST. Measuring time: 0, 9 months 13. Executive function. Measured by Litvan Frontal Assessment Battery (FAB). Measuring time: 0, 9 months 14. Selective attention (Measured by Stroop test). Measuring time:: 0, 9 months 15. Focused attention (Measured by Stroop test). Measuring time: 0, 9 months 16. Visuoconstructive function (Measured by Fig. De Rey). Measuring time: 0, 9 months 17. Visual memory (Measured by Fig. Of Rey). Measuring time:: 0, 9 months 18. Level of anxiety. Measured by the HADS (Hospital Anxiety and Depression Scale) Hospital Anxiety and Depression Scale. Measuring time: 0, 9 months 19. Level of depression. Measured by HADS. Measuring time: 0, 9 months Related to safety: 20. Adverse Events‐AE (Severity of AE (serious or not), Type of AE (accordint to Regulation 45/2007 CECMED), Intensity of AE (mild, moderate, serious), Causality relationship (Very likely, Likely, possible, unlikely, unrelated or non‐evaluable), Attitude about the drug (No change, dose reduction, temporary interruption of treatment, definitive discontinuation of treatment), Outcome (Reversible effect, irreversible effect, death, loss of patient follow‐up)). Measuring time: in each evaluation at 6 and 9 months and in each administration of the product. 21. Laboratory test (Hemoglobin (Normal, abnormal), Hematocrit (Normal, abnormal), Platelet count (Normal, abnormal), Leukocyte count (Normal, abnormal), Glycemia (Normal, abnormal), TGO (Normal, abnormal), TGP (Normal, abnormal), GGT (Normal, abnormal), Creatinine, (Normal, abnormal), uric acid (Normal, abnormal), urea (normal, abnormal)). Measuring time: 0, 6 and 9 months. 22. Blood pressure (mm/Hg). Measuring time: in each evaluation at 0, 6 and 9 months and in each administration of the product.