Lithium for Parkinson's: an Extension Trial

In observational studies, small daily doses of lithium from smoking cigarettes have been associated with a 77% reduced risk of developing Parkinson's disease (PD). In addition, lithium therapy has been effective in preventing neuronal death and behavioral symptoms in several PD animal models. Recently, our group has shown 24-weeks of low-dose lithium therapy in PD to be associated with improvements in both MRI and blood-based biomarkers implying that lithium may be slowing the progression of the disease. However, these findings stemmed from only three of four patients receiving MRIs. Our group is now conducting two larger studies enrolling a total of 35 PD patients who are being treated with either 45mg/day or 20mg/day of lithium or placebo therapy for 24 weeks. Because our earlier study showed maximum improvements in PD biomarkers in patients with serum lithium levels of 0.25-0.50mmol/L and there are large interpatient variations in serum lithium levels achieved from the same lithium dosage, this present study will adjust lithium dosing in each patient to achieve this target serum lithium level for an additional 24 weeks. MRI and blood-based biomarker changes from Baseline will be compared in patients with serum lithium levels ≥ 0.25mmol/L and \<0.25mmol/L from one of the 24-week studies and within individual patients. Results from this study may identify a target serum lithium level range associated with maximum improvements in PD biomarkers that can be used in the design of future, larger lithium PD lithium trials, which may eventually support lithium as a disease-modifying therapy for PD that could improve patients' long-term prognoses.

• Peripheral blood mononuclear cell (PBMC) Nurr1 mRNA levels by real-time polymerase chain reaction (PCR) [Срок оценки: 24 weeks]
• PBMC superoxide dismutase 1 (SOD-1) mRNA levels [Срок оценки: 24 weeks]
• PBMC phosphorylated (p) and total (t) levels of pS9 and total-glycogen synthase kinase 3B (GSK-3B) [Срок оценки: 24 weeks]
• PBMC pThr308, pS473 and t-protein kinase B (Akt) [Срок оценки: 24 weeks]
• Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III [Срок оценки: 24 weeks]
• Parkinson's Anxiety Scale [Срок оценки: 24 weeks]
• Geriatric Depression Scale-15 [Срок оценки: 24 weeks]
• Fatigue Severity Scale [Срок оценки: 24 weeks]
• Insomnia Severity Index [Срок оценки: 24 weeks]
• Parkinson's Disease Questionnaire-8 [Срок оценки: 24 weeks]
• Montreal Cognitive Assessment (MoCA) [Срок оценки: 24 weeks]