Medium-Dose Lithium May Hit Parkinson Disease Targets, but Tolerability Questioned

Medium-dose lithium aspartate therapy was associated with increases in blood-based targets and improvements in disease-progression biomarkers in a small pilot study of patients with Parkinson disease, according to a results published online in IBRO Neuroscience Reports.

“However, two of the six patients receiving this lithium dosage withdrew from the study due to side effects,” reported corresponding author Thomas Guttuso Jr., MD, of the University at Buffalo Department of Neurology, Clinical, and Translational Science Institute in Buffalo, New York, and study coauthors.

The open-label clinical trial investigated the effects of lithium, which has shown promise in animal models of Parkinson disease, in 16 people with Parkinson disease. The study randomized 5 patients to “high dose” lithium (lithium carbonate titrated to achieve serum level of 0.4–0.5 mmol/L), 6 patients to “medium-dose” lithium (45 mg/day of lithium aspartate), or 5 patients to “low-dose” lithium (15 mg/day of lithium aspartate) over 24 weeks.

According to the study, patients who received medium-dose lithium therapy demonstrated a 679% increase in peripheral blood mononuclear cell (PBMC) mRNA expression of nuclear receptor-related-1 (Nurr1) and a 127% increase in superoxide dismutase-1 (SOD1) expression, both of which are therapeutic targets in Parkinson disease. 

Among a subset of patients who underwent magnetic resonance imaging, only those who received medium-dose lithium therapy had numerical decreases in brain free water in the dorsomedial nucleus of the thalamus and nucleus basalis of Meynert, which reflect cognitive decline, and the posterior substantia nigra, which reflects motor decline. The demonstrated free water decreases are opposite of known longitudinal changes in Parkinson disease, researchers explained.

Yet a third of the patients receiving medium-dose lithium therapy withdrew because of side effects, while no patients receiving high- or low-dose lithium reported any side effects.

“Because lithium’s side effects are typically dose-dependent, it is unclear what accounted for these findings,” researchers wrote, “considering that the mean serum lithium levels were 55% higher in the high-dose group compared to the medium-dose group.”

Reference:
Guttuso T Jr, Shepherd R, Frick L, et al. Lithium’s effects on therapeutic targets and MRI biomarkers in Parkinson’s disease: a pilot clinical trial. IBRO Neurosci Rep. 2023;14:429-434. doi:10.1016/j.ibneur.2023.05.001