Objective: To evaluate the effect of levodopa on the blood activity of calpains in patients with PD

Background: Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that develops as a result of degeneration of dopaminergic neurons, predominantly in the substantia nigra (SN) (1). Calpain, a calcium-activated cysteine ​​neutral protease, plays a pivotal role in SN degeneration in PD via its role in α-synuclein aggregation. It was shown that the activity of calpains increases in PD (2), while the activity of calpains in plasma of patients at the stage 2.5-3.0 was significantly higher in comparison with patients at the stage 1.0-2.0 (3). With the progression of the disease, an increase in the dose of levodopa is required and the pharmacological response becomes unstable. It is possible that levodopa increases the activity of calpains, since calpain inhibitors suppress dyskinesias (4).

Method: The study included 16 patients with PD with stage 2.5 on the Hoehn and Yahr scale. The group consisted of 7 men and 9 women aged 48 to 85 years. Patients were divided into three subgroups, depending on the dose of levodopa – without levodopa, daily dose up to 600 mg, daily dose above 750 mg. Calpain activity was determined using a commercial kit based on a fluorescent substrate. Differences were established by ANOVA followed by Tukey’s test.

Results: It turned out that in patients with the same stage of development of PD (2.5), the total activity of calpains in blood plasma depends on the dose of levodopa: F(2, 12)=17.464, p=.00028. In patients without levodopa, the activity of calpains was (1.00 + – 0.11) conventional units; when taking levodopa at a daily dose of 375 mg – (1.04 + – 0.16) units and did not differ from the group without levodopa therapy. If a daily dose of 750 mg and more was used, then the activity of calpains decreased by 5 times and amounted to (0.18 + – 0.04) conventional units, which significantly differed from the group without levodopa p=0.0003 and from the group 375 – p=0.00021.

Conclusion: Thus, the use of levodopa at a daily dose of 750 mg and above leads to a decrease in the activity of blood calpains, which must be taken into account when developing therapeutic regimens.

References: 1. Jellinger KA. Neuropathology of sporadic Parkinson’s disease: evaluation and changes of concepts. Mov Disord. 2012 Jan;27(1):8-30. doi: 10.1002/mds.23795.
2. Gao A, McCoy HM, Zaman V, Shields DC, Banik NL, Haque A. Calpain activation and progression of inflammatory cycles in Parkinson’s disease. Front Biosci (Landmark Ed). 2022 Jan 13;27(1):20. doi: 10.31083/j.fbl2701020.
3. Muruzheva ZM, Traktirov DS, Zubov AS, Pestereva NS, Tikhomirova MS, Karpenko MN. Calpain activity in plasma of patients with essential tremor and Parkinson’s disease: a pilot study. Neurol Res. 2021 Apr;43(4):314-320. doi: 10.1080/01616412.2020.1854004.
4. Chagniel L, Robitaille C, Lebel M, Cyr M. Striatal inhibition of calpains prevents levodopa-induced neurochemical changes and abnormal involuntary movements in the hemiparkinsonian rat model. Neurobiol Dis. 2012 Jan;45(1):645-55. doi: 10.1016/j.nbd.2011.10.011.

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