Cilostazol in Parkinson's Disease

Summary

Parkinson's disease is the second most common neurodegenerative diseases. The conventional treatment for PD has included dopaminergic treatment as Levodopa\\carbidopa or dopamine agonists, anti-cholinergics, MAOI, catechol-o-methyl transferase (COMT) inhibitors, and amantadine. Although these options have been found to be effective, they could only improve the disease symptoms, but do not modify the disease progression. Hence, researchers have focused on developing disease-modifying agents to stop or slow the progression acting as neuroprotective agents. Since the inflammation and oxidative stress play an important role in the pathophysiologic progression of PD, recent studies have investigated the mitigation of the disease pathology through anti-inflammatory and anti-oxidant agents. Cilostazol has been found to have anti-inflammatory, antioxidant, and neuroprotective effect, and has been evaluated through two animal studies to prove that it possess these effects through dampening NF-κB, and its downstream effectors including TNF-α and IL-1β, reversing the activation of glycogen synthase kinase-3 β (GSK-3β), a pivotal effector in neuronal apoptosis, contributing in preserving dopaminergic neuron integrity clarifying the enhance motor activity, activating nuclear factor erythroid-related factor 2/ heme oxygenase 1 (Nrf2/HO-1), suppressing High mobility group box 1 protein/Toll-like receptor 4 (HMGB1/TLR4) axis, and upregulatig Phosphoinositide 3-kinases/ Protein kinase B (PI3K/Akt) besides mammalian target of rapamycin (mTOR) inhibition. Hence, Cilostazol might be a potential candidate to improve the clinical outcome in PD patients.

Timeline

Start

2024-10-01

Primary completion

2025-10-01

Completion

2025-10-01

Publications

• Background Abdallah MS, Ramadan AN, Omara-Reda H, Mansour NO, Elsokary MA, Elsawah HK, Zaki SA, Abo Mansour HE, Mosalam EM. Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder. CNS Neurosci Ther. 2021 Dec;27(12):1540-1548. doi: 10.1111/cns.13731. Epub 2021 Sep 21.
• Background Arai H, Takahashi T. A combination therapy of donepezil and cilostazol for patients with moderate Alzheimer disease: pilot follow-up study. Am J Geriatr Psychiatry. 2009 Apr;17(4):353-4. doi: 10.1097/JGP.0b013e31819431ea. No abstract available.
• Background Holden SK, Finseth T, Sillau SH, Berman BD. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort. Mov Disord Clin Pract. 2018 Jan-Feb;5(1):47-53. doi: 10.1002/mdc3.12553. Epub 2017 Sep 22.
• Background Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993 Jan 21;328(3):176-83. doi: 10.1056/NEJM199301213280305.
• Background Hedya SA, Safar MM, Bahgat AK. Cilostazol Mediated Nurr1 and Autophagy Enhancement: Neuroprotective Activity in Rat Rotenone PD Model. Mol Neurobiol. 2018 Sep;55(9):7579-7587. doi: 10.1007/s12035-018-0923-1. Epub 2018 Feb 10.
• Background Howells DW, Porritt MJ, Wong JY, Batchelor PE, Kalnins R, Hughes AJ, Donnan GA. Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Exp Neurol. 2000 Nov;166(1):127-35. doi: 10.1006/exnr.2000.7483.
• Background Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
• Background Rahman TT, El Gaafary MM. Montreal Cognitive Assessment Arabic version: reliability and validity prevalence of mild cognitive impairment among elderly attending geriatric clubs in Cairo. Geriatr Gerontol Int. 2009 Mar;9(1):54-61. doi: 10.1111/j.1447-0594.2008.00509.x.
• Background Safiri S, Noori M, Nejadghaderi SA, Mousavi SE, Sullman MJM, Araj-Khodaei M, Singh K, Kolahi AA, Gharagozli K. The burden of Parkinson's disease in the Middle East and North Africa region, 1990-2019: results from the global burden of disease study 2019. BMC Public Health. 2023 Jan 16;23(1):107. doi: 10.1186/s12889-023-15018-x.
• Background Sakamoto T, Ohashi W, Tomita K, Hattori K, Matsuda N, Hattori Y. Anti-inflammatory properties of cilostazol: Its interruption of DNA binding activity of NF-kappaB from the Toll-like receptor signaling pathways. Int Immunopharmacol. 2018 Sep;62:120-131. doi: 10.1016/j.intimp.2018.06.021. Epub 2018 Jul 10.

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Indications