Objective: The objective of this report is to investigate the effect of Levodopa therapy on calpain activity in patients with advanced stages of Parkinson’s disease to elucidate its potential disease-modifying properties.

Background: Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of pathological proteins, a process in which calcium-dependent proteases, calpains, play a key role. Levodopa remains the gold standard for symptomatic treatment; however, its impact on the molecular mechanisms of neurodegeneration, particularly calpain activity, remains unclear.

Method: The study enrolled 60 patients, aged 60 to 85 years, diagnosed with Parkinson’s disease at stage 2.5 according to the Hoehn and Yahr scale. Calpain activity was measured using fluorescent substrate method.

Results: The patients with Parkinson’s disease were divided into three subgroups based on their levodopa dosage. A comparative analysis of calpain activity revealed significant differences between the groups. Specifically, calpain activity was significantly higher in patients at Hoehn and Yahr stage 2.5 who were not receiving levodopa therapy (Subgroup 1) compared to those who were treated with levodopa.

When comparing the subgroups, the following p-values were obtained: between Subgroup 1 (no levodopa) and Subgroup 2 (180–375 mg/day), the difference in calpain activity was statistically significant (p = 0.005). A trend towards significance was observed when comparing Subgroup 1 with Subgroup 3 (625–1250 mg/day) (p = 0.096). However, no statistically significant difference in calpain activity was found between the two levodopa-treated subgroups (p = 0.178).

Conclusion: The findings indicate that levodopa therapy is associated with reduced calpain activity in patients with advanced Parkinson’s disease. Patients not receiving levodopa demonstrated significantly higher calpain activity compared to those on treatment. However, the lack of significant difference between the low-dose and high-dose groups suggests that the observed effect may not be dose-dependent within the therapeutic range. These results support the potential disease-modifying properties of levodopa through modulation of calcium-dependent proteolysis, though further research is warranted to elucidate the underlying mechanisms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-levodopa-on-calpain-activity-in-patients-with-parkinsons-disease/