Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: A Phase I Trial

In observational studies, small daily doses of lithium 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 aspartate therapy 45mg/day in PD to engage blood-based and the MRI disease progression biomarker, free water, to a greater extent than 15mg/day or 150mg/day of lithium carbonate. However, these blood-based and MRI biomarker findings stem from only four and two PD patients, respectively, who received lithium aspartate 45mg/day. In addition, two other PD patients receiving this dosage withdrew from the study due to side effects of sedation and dizziness. Subsequently, one of these patients who withdrew resumed lithium aspartate at 30mg/day and reported no side effects. Although these findings suggest that this dosage of lithium aspartate has positive effects on PD biomarkers, data from a larger number of PD patients will be required to justify conducting a larger, randomized controlled trial (RCT). The proposed study will enroll 15 additional PD patients over five months who will receive lithium aspartate 30-45mg/day for 24 weeks ensuring that the study will be completed within 12 months. The dosage will be slowly titrated in each patient up to the maximum tolerated dosage in this range. Blood-based biomarkers and MRIs will be assessed at baseline and 24 weeks. It is anticipated that a similar magnitude of biomarker engagement will be observed among these additional 15 patients as was seen in the handful from the pilot study. Such findings would provide strong preliminary evidence to support conducting a larger RCT including both clinical and biomarker outcomes. Positive results from such a RCT would support lithium aspartate as a disease-modifying therapy for PD.