Lithium carbonate has been investigated as a potential disease-modifying treatment for Progressive Supranuclear Palsy (PSP) based on its neuroprotective properties. Lithium inhibits glycogen synthase kinase-3 beta (GSK-3β), a key kinase involved in tau phosphorylation. Despite strong preclinical rationale, clinical trials in PSP have shown limited efficacy.[1][2]
| Parameter | Details |
|---|---|
| Drug Name | Lithium Carbonate |
| Mechanism | GSK-3β inhibitor |
| Phase | Phase 2 |
| Status | Completed |
| Key Trial | NCT00703677 |
Lithium exerts several neuroprotective effects relevant to PSP:
The rationale for lithium in PSP is strong:
The primary clinical trial (NCT00703677) was a Phase 2 randomized, double-blind, placebo-controlled trial conducted at multiple centers to evaluate lithium carbonate in patients with PSP[2:1][3].
Trial Design:
Key Findings:
| Outcome | Result |
|---|---|
| Primary (PSPRS change) | No significant difference vs placebo |
| Tau biomarkers | No significant reduction in CSF tau |
| Tolerability | Acceptable safety profile |
| Discontinuation | 20% (due to side effects or disease progression) |
Published Results (Hampel et al., 2009):
Interpretation:
The negative trial results suggested several possibilities:
Despite negative results, this trial provided valuable insights:
Several other GSK-3β inhibitors have been explored in tauopathies:
CHIR99021 - Preclinical
Valproic acid - Also has GSK-3β effects, failed in PSP (NCT00385710)
Hampel H, et al. Lithium for the treatment of patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled trial. J Clin Psychiatry. 2009. ↩︎ ↩︎
Tolosa E, et al. Lithium in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2009. ↩︎