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Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Mini-Review Article

Treatment of Parkinson's Disease: Current Treatments and Recent Therapeutic Developments

Author(s): Ankita Wal, Pranay Wal*, Himangi Vig, Nem Kumar Jain, Shruti Rathore, Karthickeyan Krishnan and Ashish Srivastava

Volume 20, Issue 5, 2023

Published on: 21 June, 2023

Article ID: e120523216834 Pages: 17

DOI: 10.2174/1570163820666230512100340

Price: $65

Abstract

Background: Parkinson’s disease (PD) is a neurodegenerative syndrome defined by a variety of motor, cognitive, and psychomotor dysfunctions. The current pharmaceutical treatment focuses on treating the condition's symptoms. They are primarily concerned with reducing illness symptoms or avoiding dopamine metabolism. As our understanding of disease pathogenesis improves, new therapeutic approaches emerge.

Objective: This article aims to describe the standard Parkinson's medications based on symptoms and requirements. It emphasizes recent advancements in symptomatic therapy for motor indications and achievements in the research and clinical testing of medicines that promise to enable disease modification in patients with already-manifest PD.

Methods: Information for this paper was found by looking through Google Scholar and reading several research and review articles from Bentham Science, Science Direct, Elsevier, Frontiers, Taylor & Francis, and other publishers.

Result: Parkinson's disease therapeutic interventions are now limited to symptomatic therapy, mostly in dopaminergic medications and deep brain stimulation (DBS). They have the potential to deliver great therapeutic progress, yet they can also have serious drawbacks that decrease a patient's quality of life. The progress of pluripotent stem cell therapies and genome engineering procedures has sparked renewed hope for the treatment of a wide range of human illnesses, particularly genetic abnormalities.

Conclusion: The current Parkinson's therapy trends are successful and continually evolving, with several drugs currently undergoing clinical trials. As these new therapies constantly coming out and can be used together, they will likely change how Parkinson's disease is treated in the coming years.

Graphical Abstract

[1]
Dickson DW, Braak H, Duda JE, et al. Neuropathological assessment of Parkinson’s disease: Refining the diagnostic criteria. Lancet Neurol 2009; 8(12): 1150-7.
[http://dx.doi.org/10.1016/S1474-4422(09)70238-8] [PMID: 19909913]
[2]
Wal P, Dwivedi J, Wal A, Vig H, Singh Y. Detailed insight into the pathophysiology and the behavioral complications associated with the Parkinson’s disease and its medications. Future J Pharm Sci 2022; 8(1): 33.
[http://dx.doi.org/10.1186/s43094-022-00425-5]
[3]
Striessnig J, Ortner N, Pinggera AJ, Ortner N, Pinggera A. Pharmacology of L-type calcium channels: Novel drugs for old targets? Curr Mol Pharmacol 2015; 8(2): 110-22.
[http://dx.doi.org/10.2174/1874467208666150507105845] [PMID: 25966690]
[4]
Khoo TK, Yarnall AJ, Duncan GW, et al. The spectrum of nonmotor symptoms in early Parkinson disease. Neurology 2013; 80(3): 276-81.
[http://dx.doi.org/10.1212/WNL.0b013e31827deb74] [PMID: 23319473]
[5]
Sulzer D, Alcalay RN, Garretti F, et al. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 2017; 546(7660): 656-61.
[http://dx.doi.org/10.1038/nature22815] [PMID: 28636593]
[6]
Dumane VA, Hunt MA, Green S, Lo YC, Bakst RL. Dosimetric comparison of volumetric modulated arc therapy, static field intensity modulated radiation therapy, and 3D conformal planning for the treatment of a right-sided reconstructed chest wal and regional nodal case. J Radiother 2014; 2014: 1-12.
[http://dx.doi.org/10.1155/2014/835179]
[7]
Stoker TB, Barker RA. Recent developments in the treatment of Parkinson’s Disease. F1000 Res 2020; 9: 862.
[http://dx.doi.org/10.12688/f1000research.25634.1] [PMID: 32789002]
[8]
Tambasco N, Romoli M, Calabresi P. Levodopa in Parkinson’s disease: Current status and future developments. Curr Neuropharmacol 2018; 16(8): 1239-52.
[http://dx.doi.org/10.2174/1570159X15666170510143821] [PMID: 28494719]
[9]
Li J, Lou Z, Liu X, Sun Y, Chen J. Efficacy and safety of adjuvant treatment with entacapone in advanced Parkinson’s disease with motor fluctuation: A systematic meta-analysis. Eur Neurol 2017; 78(3-4): 143-53.
[http://dx.doi.org/10.1159/000479555] [PMID: 28813703]
[10]
Ruan X, Lin F, Wu D, et al. Comparative efficacy and safety of dopamine agonists in advanced Parkinson’s disease with motor fluctuations: A systematic review and network meta-analysis of double-blind randomized controlled trials. Front Neurosci 2021; 15: 728083.
[http://dx.doi.org/10.3389/fnins.2021.728083] [PMID: 34776841]
[11]
Myette-Côté É, Soto-Mota A, Cunnane SC. Ketones: Potential to achieve brain energy rescue and sustain cognitive health during ageing. Br J Nutr 2022; 128(3): 407-23.
[http://dx.doi.org/10.1017/S0007114521003883] [PMID: 34581265]
[12]
Fahn S. The medical treatment of Parkinson disease from James Parkinson to George Cotzias. Mov Disord 2015; 30(1): 4-18.
[http://dx.doi.org/10.1002/mds.26102] [PMID: 25491387]
[13]
Tripathi KD. Essentials of medical pharmacology 2013.
[http://dx.doi.org/10.5005/jp/books/12256]
[14]
Ba F, Martin WRW. Dopamine transporter imaging as a diagnostic tool for parkinsonism and related disorders in clinical practice. Parkinsonism Relat Disord 2015; 21(2): 87-94.
[http://dx.doi.org/10.1016/j.parkreldis.2014.11.007] [PMID: 25487733]
[15]
Kwak N, Park J, Kang HY, Lee MJ, Suh JK, Lee H. Efficacy and safety of opicapone for motor fluctuations as an adjuvant to levodopa therapy in patient with parkinson’s disease: A systematic review and meta-analysis. J Parkinsons Dis 2022; 12(3): 773-83.
[16]
Pezzoli G, Zini M. Levodopa in Parkinson’s disease: From the past to the future. Expert Opin Pharmacother 2010; 11(4): 627-35.
[http://dx.doi.org/10.1517/14656561003598919] [PMID: 20163273]
[17]
Yoo HS, Chung SJ, Chung SJ, et al. Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease. Eur J Nucl Med Mol Imaging 2018; 45(3): 423-31.
[http://dx.doi.org/10.1007/s00259-017-3844-8] [PMID: 29075830]
[18]
Blesa J, Juri C, García-Cabezas MÁ, et al. Inter-hemispheric asymmetry of nigrostriatal dopaminergic lesion: A possible compensatory mechanism in Parkinson’s disease. Front Syst Neurosci 2011; 5: 92.
[http://dx.doi.org/10.3389/fnsys.2011.00092] [PMID: 22287944]
[19]
Fabbri M, Ferreira JJ, Rascol O. COMT Inhibitors in the Management of Parkinson’s Disease. CNS Drugs 2022; 36(3): 261-82.
[http://dx.doi.org/10.1007/s40263-021-00888-9] [PMID: 35217995]
[20]
Finberg JPM, Rabey JM. Inhibitors of MAO-A and MAO-B in psychiatry and neurology. Front Pharmacol 2016; 7: 340.
[http://dx.doi.org/10.3389/fphar.2016.00340] [PMID: 27803666]
[21]
DeLong MR, Huang KT, Gallis J, et al. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol 2014; 71(10): 1290-5.
[http://dx.doi.org/10.1001/jamaneurol.2014.1272] [PMID: 25155481]
[22]
Robottom B. Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson’s disease. Patient Prefer Adherence 2011; 5: 57-64.
[http://dx.doi.org/10.2147/PPA.S11182] [PMID: 21423589]
[23]
Robottom B, Weiner W. Parkinsons disease dementia. Curr Psychiatry Rev 2009; 5(3): 218-25.
[http://dx.doi.org/10.2174/157340009788971128] [PMID: 19501721]
[24]
Shih JC. Monoamine oxidase isoenzymes: Genes, functions and targets for behavior and cancer therapy. J Neural Transm (Vienna) 2018; 125(11): 1553-66.
[http://dx.doi.org/10.1007/s00702-018-1927-8] [PMID: 30259128]
[25]
Puttrevu SK, Arora S, Polak S, Patel NK. Physiologically based pharmacokinetic modeling of transdermal selegiline and its metabolites for the evaluation of disposition differences between healthy and special populations. Pharmaceutics 2020; 12(10): 942.
[http://dx.doi.org/10.3390/pharmaceutics12100942] [PMID: 33008144]
[26]
Aquilonius SM, Nyholm D. Development of new levodopa treatment strategies in Parkinson’s disease-from bedside to bench to bedside. Ups J Med Sci 2017; 122(2): 71-7.
[http://dx.doi.org/10.1080/03009734.2017.1285374] [PMID: 28276779]
[27]
Santos SF, de Oliveira HL, Yamada ES, Neves BC, Pereira A Jr. The gut and Parkinsons disease-A bidirectional pathway. Front Neurol 2019; 10: 574.
[http://dx.doi.org/10.3389/fneur.2019.00574] [PMID: 31214110]
[28]
Raza C, Anjum R, Shakeel NA. Parkinson’s disease: Mechanisms, translational models and management strategies. Life Sci 2019; 226: 77-90.
[http://dx.doi.org/10.1016/j.lfs.2019.03.057] [PMID: 30980848]
[29]
Finotti N, Castagna L, Moretti A, Marzatico F. Reduction of lipid peroxidation in different rat brain areas after cabergoline treatment. Pharmacol Res 2000; 42(4): 287-91.
[http://dx.doi.org/10.1006/phrs.2000.0690] [PMID: 10987985]
[30]
Marvanova M, Nichols CD. Identification of neuroprotective compounds of Caenorhabditis elegans dopaminergic neurons against 6-OHDA. J Mol Neurosci 2007; 31(2): 127-37.
[http://dx.doi.org/10.1385/JMN/31:02:127] [PMID: 17478886]
[31]
Sayeed I, Parvez S, Winkler-Stuck K, et al. Patch clamp reveals powerful blockade of the mitochondrial permeability transition pore by the D2‐receptor agonist pramipexole. FASEB J 2006; 20(3): 556-8.
[http://dx.doi.org/10.1096/fj.05-4748fje] [PMID: 16407457]
[32]
Cho JW, Park J, Kim Y, et al. Levodopa dose maintenance or reduction in patients with Parkinson’s disease transitioning to levodopa/carbidopa/entacapone. Neurol India 2017; 65(4): 746-51.
[http://dx.doi.org/10.4103/neuroindia.NI_597_16] [PMID: 28681744]
[33]
Nagatsu T, Nagatsu I. Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson’s disease (PD): Historical overview and future prospects. J Neural Transm (Vienna) 2016; 123(11): 1255-78.
[http://dx.doi.org/10.1007/s00702-016-1596-4] [PMID: 27491309]
[34]
Kaur D, Peng J, Chinta SJ, et al. Increased murine neonatal iron intake results in Parkinson-like neurodegeneration with age. Neurobiol Aging 2007; 28(6): 907-13.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.04.003] [PMID: 16765489]
[35]
Filograna R, Beltramini M, Bubacco L, Bisaglia M. Anti-oxidants in Parkinson’s disease therapy: A critical point of view. Curr Neuropharmacol 2016; 14(3): 260-71.
[36]
Wal A, Wal P, Vig H, Samad A, Khandai M, Tyagi S. A Systematic review of various in-vivo screening models as well as the mechanisms involved in Parkinson’s disease screening procedures. n: Curr Rev Clin Exp Pharmacol. 2022.
[37]
Zhang H, Ye N, Zhou S, et al. Identification of N-propylnoraporphin-11-yl 5-(1,2-dithiolan-3-yl)pentanoate as a new anti-Parkinson’s agent possessing a dopamine D2 and serotonin 5-HT1A dual-agonist profile. J Med Chem 2011; 54(13): 4324-38.
[http://dx.doi.org/10.1021/jm200347t] [PMID: 21591752]
[38]
Mao Q, Qin W, Zhang A, Ye N. Recent advances in dopaminergic strategies for the treatment of Parkinson’s disease. Acta Pharmacol Sin 2020; 41(4): 471-82.
[http://dx.doi.org/10.1038/s41401-020-0365-y] [PMID: 32112042]
[39]
Zhao R, Lu W, Fang X, et al. (6aR)-11-Amino-N-propyl-noraporphine, a new dopamine D2 and serotonin 5-HT1A dual agonist, elicits potent antiparkinsonian action and attenuates levodopa-induced dyskinesia in a 6-OHDA-lesioned rat model of Parkinson’s disease. Pharmacol Biochem Behav 2014; 124(124): 204-10.
[http://dx.doi.org/10.1016/j.pbb.2014.06.011] [PMID: 24955866]
[40]
Huot P, Sgambato-Faure V, Fox SH, McCreary AC. Serotonergic approaches in Parkinson’s disease: Translational perspectives, an update. ACS Chem Neurosci 2017; 8(5): 973-86.
[http://dx.doi.org/10.1021/acschemneuro.6b00440] [PMID: 28460160]
[41]
Hall A, Provins L, Valade A. Novel strategies to activate the dopamine D1 receptor: Recent advances in orthosteric agonism and positive allosteric modulation. J Med Chem 2019; 62(1): 128-40.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01767] [PMID: 30525590]
[42]
Gray DL, Allen JA, Mente S, et al. Impaired β-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor. Nat Commun 2018; 9(1): 674.
[http://dx.doi.org/10.1038/s41467-017-02776-7] [PMID: 29445200]
[43]
Lindenbach D, Das B, Conti MM, Meadows SM, Dutta AK, Bishop C. D-512, a novel dopamine D 2/3 receptor agonist, demonstrates greater anti-Parkinsonian efficacy than ropinirole in Parkinsonian rats. Br J Pharmacol 2017; 174(18): 3058-71.
[http://dx.doi.org/10.1111/bph.13937] [PMID: 28667675]
[44]
Modi G, Voshavar C, Gogoi S, et al. Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: Modulator of toxicity of alpha-synuclein aggregates. ACS Chem Neurosci 2014; 5(8): 700-17.
[http://dx.doi.org/10.1021/cn500084x] [PMID: 24960209]
[45]
Zhang J, Xiong B, Zhen X, Zhang A. Dopamine D 1 receptor ligands: Where are we now and where are we going. Med Res Rev 2009; 29(2): 272-94.
[http://dx.doi.org/10.1002/med.20130] [PMID: 18642350]
[46]
Das B, Rajagopalan S, Joshi GS, et al. A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo. Neuropharmacology 2017; 123: 88-99.
[http://dx.doi.org/10.1016/j.neuropharm.2017.05.019] [PMID: 28533164]
[47]
Elmabruk A, Das B, Yedlapudi D, et al. Design, synthesis, and pharmacological characterization of carbazole based dopamine agonists as potential symptomatic and neuroprotective therapeutic agents for Parkinson’s disease. ACS Chem Neurosci 2019; 10(1): 396-411.
[http://dx.doi.org/10.1021/acschemneuro.8b00291] [PMID: 30301349]
[48]
Das B, Kandegedara A, Xu L, et al. A novel iron (II) preferring dopamine agonist chelator as potential symptomatic and neuroprotective therapeutic agent for Parkinson’s disease. ACS Chem Neurosci 2017; 8(4): 723-30.
[http://dx.doi.org/10.1021/acschemneuro.6b00356] [PMID: 28106982]
[49]
Cote SR, Kuzhikandathil EV. In vitro and in vivo characterization of the agonist-dependent D3 dopamine receptor tolerance property. Neuropharmacology 2014; 79: 359-67.
[http://dx.doi.org/10.1016/j.neuropharm.2013.11.023] [PMID: 24316466]
[50]
Xu W, Wang X, Tocker AM, et al. Functional characterization of a novel series of biased signaling dopamine D3 receptor agonists. ACS Chem Neurosci 2017; 8(3): 486-500.
[http://dx.doi.org/10.1021/acschemneuro.6b00221] [PMID: 27801563]
[51]
Volpini R, Dal Ben D, Lambertucci C, et al. Adenosine A2A receptor antagonists: New 8-substituted 9-ethyladenines as tools for in vivo rat models of Parkinson’s disease. ChemMedChem 2009; 4(6): 1010-9.
[http://dx.doi.org/10.1002/cmdc.200800434] [PMID: 19343763]
[52]
Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M. Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci 2006; 29(11): 647-54.
[http://dx.doi.org/10.1016/j.tins.2006.09.004] [PMID: 17030429]
[53]
Pinna A. Adenosine A2A receptor antagonists in Parkinson’s disease: Progress in clinical trials from the newly approved istradefylline to drugs in early development and those already discontinued. CNS Drugs 2014; 28(5): 455-74.
[http://dx.doi.org/10.1007/s40263-014-0161-7] [PMID: 24687255]
[54]
Mallet N, Delgado L, Chazalon M, Miguelez C, Baufreton J. Cellular and synaptic dysfunctions in Parkinson’s disease: Stepping out of the striatum. Cells 2019; 8(9): 1005.
[http://dx.doi.org/10.3390/cells8091005] [PMID: 31470672]
[55]
Sebastianutto I, Cenci MA. mGlu receptors in the treatment of Parkinson’s disease and L-DOPA-induced dyskinesia. Curr Opin Pharmacol 2018; 38: 81-9.
[http://dx.doi.org/10.1016/j.coph.2018.03.003] [PMID: 29625424]
[56]
Armentero MT, Pinna A, Ferré S, Lanciego JL, Müller CE, Franco R. Past, present and future of A2A adenosine receptor antagonists in the therapy of Parkinson’s disease. Pharmacol Ther 2011; 132(3): 280-99.
[http://dx.doi.org/10.1016/j.pharmthera.2011.07.004] [PMID: 21810444]
[57]
Blesa J, Trigo-Damas I, Dileone M, del Rey NLG, Hernandez LF, Obeso JA. Compensatory mechanisms in Parkinson’s disease: Circuits adaptations and role in disease modification. Exp Neuro 2017; 298((Pt B)): 148-61.
[http://dx.doi.org/10.1016/j.expneurol.2017.10.002] [PMID: 28987461]
[58]
Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson’s disease. CNS Drugs 2018; 32(4): 387-98.
[http://dx.doi.org/10.1007/s40263-018-0498-4] [PMID: 29532440]
[59]
Hadj Tahar A, Grégoire L, Darré A, Bélanger N, Meltzer L, Bédard PJ. Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys. Neurobiol Dis 2004; 15(2): 171-6.
[http://dx.doi.org/10.1016/j.nbd.2003.10.007] [PMID: 15006686]
[60]
Wu SS, Frucht SJ. Treatment of Parkinson’s disease: what’s on the horizon? CNS Drugs 2005; 19(9): 723-43.
[http://dx.doi.org/10.2165/00023210-200519090-00001] [PMID: 16142989]
[61]
Chen JF, Cunha RA. The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic Signal 2020; 16(2): 167-74.
[http://dx.doi.org/10.1007/s11302-020-09694-2] [PMID: 32236790]
[62]
Jenner P, Mori A, Aradi SD, Hauser RA. Istradefylline – a first generation adenosine A 2A antagonist for the treatment of Parkinson’s disease. Expert Rev Neurother 2021; 21(3): 317-33.
[http://dx.doi.org/10.1080/14737175.2021.1880896] [PMID: 33507105]
[63]
Wojtecki L, Groiss S, Hartmann C, et al. Deep brain stimulation in Huntington’s disease—preliminary evidence on pathophysiology, efficacy and safety. Brain Sci 2016; 6(3): 38.
[http://dx.doi.org/10.3390/brainsci6030038] [PMID: 27589813]
[64]
Bello F, Giannella M, Giorgioni G, Piergentili A, Quaglia W. Receptor ligands as helping hands to L-DOPA in the treatment of Parkinson’s disease. Biomolecules 2019; 9(4): 142.
[http://dx.doi.org/10.3390/biom9040142] [PMID: 30970612]
[65]
Lees A, Fahn S, Eggert KM, et al. Perampanel, an AMPA antagonist, found to have no benefit in reducing “off” time in Parkinson’s disease. Mov Disord 2012; 27(2): 284-8.
[http://dx.doi.org/10.1002/mds.23983] [PMID: 22161845]
[66]
Rascol O, Barone P, Behari M, et al. Perampanel in Parkinson disease fluctuations: A double-blind randomized trial with placebo and entacapone. Clin Neuropharmacol 2012; 35(1): 15-20.
[http://dx.doi.org/10.1097/WNF.0b013e318241520b] [PMID: 22222634]
[67]
Clarke CE, Cooper JA, Holdich TAH. A randomized, double-blind, placebo-controlled, ascending-dose tolerability and safety study of remacemide as adjuvant therapy in Parkinson’s disease with response fluctuations. Clin Neuropharmacol 2001; 24(3): 133-8.
[http://dx.doi.org/10.1097/00002826-200105000-00003] [PMID: 11391123]
[68]
Ramirez-Zamora A, Molho E. Treatment of motor fluctuations in Parkinson’s disease: Recent developments and future directions. Expert Rev Neurother 2014; 14(1): 93-103.
[http://dx.doi.org/10.1586/14737175.2014.868306] [PMID: 24328720]
[69]
Barnum CJ, Bhide N, Lindenbach D, et al. Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats. Pharmacol Biochem Behav 2012; 100(3): 607-15.
[http://dx.doi.org/10.1016/j.pbb.2011.09.009] [PMID: 21978941]
[70]
Bogetofte H, Alamyar A, Blaabjerg M, Meyer M. Levodopa therapy for Parkinson’s disease: History, current status and perspectives. CNS Neurol Disord Drug Targets 2020; 19(8): 572-83.
[http://dx.doi.org/10.2174/1871527319666200722153156] [PMID: 32703142]
[71]
Uddin MN, Hoq MI, Jahan I, et al. The mechanistic role of thymoquinone in parkinson’s disease: Focus on neuroprotection in pre-clinical studies. Curr Mol Pharmacol 2021; 14(6): 1083-92.
[http://dx.doi.org/10.2174/1874467214666210105140944] [PMID: 33402092]
[72]
Srinivasan J, Schmidt WJ. The effect of the a 2 -adrenoreceptor antagonist idazoxan against 6-hydroxydopamine-induced Parkinsonism in rats: Multiple facets of action? Naunyn Schmiedebergs Arch Pharmacol 2004; 369(6): 629-38.
[http://dx.doi.org/10.1007/s00210-004-0929-2] [PMID: 15118809]
[73]
Schneider A, Sari AT, Alhaddad H, Sari Y. Overview of therapeutic drugs and methods for the treatment of Parkinson’s disease. CNS Neurol Disord Drug Targets 2020; 19(3): 195-206.
[http://dx.doi.org/10.2174/1871527319666200525011110] [PMID: 32448109]
[74]
Savola JM, Hill M, Engstrom M, et al. Fipamezole (JP-1730) is a potent? 2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Mov Disord 2003; 18(8): 872-83.
[http://dx.doi.org/10.1002/mds.10464] [PMID: 12889076]
[75]
Duwa R, Jeong JH, Yook S. Development of immunotherapy and nanoparticles-based strategies for the treatment of Parkinson’s disease. J Pharm Investig 2021; 51(4): 465-81.
[http://dx.doi.org/10.1007/s40005-021-00521-3]
[76]
LeWitt PA, Hauser RA, Lu M, et al. Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study). Neurology 2012; 79(2): 163-9.
[http://dx.doi.org/10.1212/WNL.0b013e31825f0451] [PMID: 22744665]
[77]
Olanow CW, Damier P, Goetz CG, et al. Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 2004; 27(2): 58-62.
[http://dx.doi.org/10.1097/00002826-200403000-00003] [PMID: 15252265]
[78]
Zella M, Metzdorf J, Ostendorf F, et al. Novel immunotherapeutic approaches to target alpha-synuclein and related neuroinflammation in Parkinson’s disease. Cells 2019; 8(2): 105.
[http://dx.doi.org/10.3390/cells8020105] [PMID: 30708997]
[79]
Zhang G, Xia Y, Wan F, et al. New perspectives on roles of alpha-synuclein in Parkinson’s disease. Front Aging Neurosci 2018; 10: 370.
[http://dx.doi.org/10.3389/fnagi.2018.00370] [PMID: 30524265]
[80]
Farzanehfar P. Comparative review of adult midbrain and striatum neurogenesis with classical neurogenesis. Neurosci Res 2018; 134: 1-9.
[http://dx.doi.org/10.1016/j.neures.2018.01.002] [PMID: 29339103]
[81]
George S, Brundin P. Immunotherapy in Parkinson’s disease: Micromanaging alpha- synuclein aggregation. J Parkinsons Dis 2015; 5(3): 413-24.
[http://dx.doi.org/10.3233/JPD-150630] [PMID: 26406122]
[82]
Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting alpha-synuclein as a therapy for Parkinson’s disease. Front Mol Neurosci 2019; 12: 299.
[http://dx.doi.org/10.3389/fnmol.2019.00299] [PMID: 31866823]
[83]
Sapru MK, Yates JW, Hogan S, Jiang L, Halter J, Bohn MC. Silencing of human α-synuclein in vitro and in rat brain using lentiviral-mediated RNAi. Exp Neurol 2006; 198(2): 382-90.
[http://dx.doi.org/10.1016/j.expneurol.2005.12.024] [PMID: 16455076]
[84]
Lewis J, Melrose H, Bumcrot D, et al. In vivo silencing of alpha-synuclein using naked siRNA. Mol Neurodegener 2008; 3(1): 19.
[http://dx.doi.org/10.1186/1750-1326-3-19] [PMID: 18976489]
[85]
McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA. α-synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PLoS One 2010; 5(8): e12122.
[http://dx.doi.org/10.1371/journal.pone.0012122] [PMID: 20711464]
[86]
Stoker TB, Torsney KM, Barker RA. Emerging treatment approaches for Parkinson’s disease. Front Neurosci 2018; 12: 693.
[http://dx.doi.org/10.3389/fnins.2018.00693] [PMID: 30349448]
[87]
Schenk DB, Koller M, Ness DK, et al. First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord 2017; 32(2): 211-8.
[http://dx.doi.org/10.1002/mds.26878] [PMID: 27886407]
[88]
Brundin P, Dave KD, Kordower JH. Therapeutic approaches to target alpha-synuclein pathology. Exp Neurol 2017; 298(Pt B): 225-35.
[http://dx.doi.org/10.1016/j.expneurol.2017.10.003] [PMID: 28987463]
[89]
Braithwaite SP, Stock JB, Mouradian MM. α-Synuclein phosphorylation as a therapeutic target in Parkinson’s disease. Rev Neurosci 2012; 23(2): 191-8.
[http://dx.doi.org/10.1515/revneuro-2011-0067] [PMID: 22499677]
[90]
Jankovic J, Goodman I, Safirstein B, et al. Safety and tolerability of multiple ascending doses of PRX002/RG7935, an anti–α-synuclein monoclonal antibody, in patients with Parkinson disease: A randomized clinical trial. JAMA Neurol 2018; 75(10): 1206-14.
[http://dx.doi.org/10.1001/jamaneurol.2018.1487] [PMID: 29913017]
[91]
Weihofen A, Liu Y, Arndt JW, et al. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models. Neurobiol Dis 2019; 124: 276-88.
[http://dx.doi.org/10.1016/j.nbd.2018.10.016] [PMID: 30381260]
[92]
Siani F, Greco R, Levandis G, et al. al. Influence of estrogen modulation on glia activation in a murine model of Parkinson’s disease. Front Neurosci 2017; 11: 306.
[http://dx.doi.org/10.3389/fnins.2017.00306] [PMID: 28620274]
[93]
Gordon R, Albornoz EA, Christie DC, et al. Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Sci Transl Med 2018; 10(465): eaah4066.
[http://dx.doi.org/10.1126/scitranslmed.aah4066] [PMID: 30381407]
[94]
Tan JSY, Chao YX, Rötzschke O, Tan EK. New insights into immune-mediated mechanisms in Parkinson’s disease. Int J Mol Sci 2020; 21(23): 9302.
[http://dx.doi.org/10.3390/ijms21239302] [PMID: 33291304]
[95]
Yun SP, Kam TI, Panicker N, et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease. Nat Med 2018; 24(7): 931-8.
[http://dx.doi.org/10.1038/s41591-018-0051-5] [PMID: 29892066]
[96]
Tamburrino A, Churchill MJ, Wan OW, et al. Cyclosporin promotes neurorestoration and cell replacement therapy in pre-clinical models of Parkinson’s disease. Acta Neuropathol Commun 2015; 3(1): 84.
[http://dx.doi.org/10.1186/s40478-015-0263-6] [PMID: 26666562]
[97]
Kim C, Spencer B, Rockenstein E, et al. Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating α-synuclein transmission and neuroinflammation. Mol Neurodegener 2018; 13(1): 43.
[http://dx.doi.org/10.1186/s13024-018-0276-2] [PMID: 29310663]
[98]
Zhou C, Emadi S, Sierks MR, Messer A. A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed α-synuclein. Mol Ther 2004; 10(6): 1023-31.
[http://dx.doi.org/10.1016/j.ymthe.2004.08.019] [PMID: 15564134]
[99]
Robertson DC, Schmidt O, Ninkina N, Jones PA, Sharkey J, Buchman VL. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ-synuclein, α-synuclein and double α/γ-synuclein null mutant mice. J Neurochem 2004; 89(5): 1126-36.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02378.x] [PMID: 15147505]
[100]
Benskey MJ, Sellnow RC, Sandoval IM, Sortwell CE, Lipton JW, Manfredsson FP. Silencing alpha synuclein in mature nigral neurons results in rapid neuroinflammation and subsequent toxicity. Front Mol Neurosci 2018; 11: 36.
[http://dx.doi.org/10.3389/fnmol.2018.00036] [PMID: 29497361]
[101]
Muramatsu S, Fujimoto K, Kato S, et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Ther 2010; 18(9): 1731-5.
[http://dx.doi.org/10.1038/mt.2010.135] [PMID: 20606642]
[102]
da Silva Oliveira GL, da Silva JCCL, Dos Santos C L da Silva AP Feitosa CM, de Castro Almeida FR Feitosa CM,, et al. Anticonvulsant, anxiolytic and antidepressant properties of the β-caryophyllene in swiss mice: Involvement of benzodiazepine-gabaaergic, serotonergic and nitrergic systems. Curr Mol Pharmacol 2021; 14(1): 36-51.
[http://dx.doi.org/10.2174/1874467213666200510004622] [PMID: 32386503]
[103]
Le Witt PA, Rezai AR, Leehey MA, et al. AAV2-GAD gene therapy for advanced Parkinson’s disease: A double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 2011; 10(4): 309-19.
[http://dx.doi.org/10.1016/S1474-4422(11)70039-4] [PMID: 21419704]
[104]
Skibinska M, Kapelski P, Pawlak J, et al. Glial Cell Line-Derived Neurotrophic Factor (GDNF) serum level in women with schizophrenia and depression, correlation with clinical and metabolic parameters. Psychiatry Res 2017; 256: 396-402.
[http://dx.doi.org/10.1016/j.psychres.2017.07.014] [PMID: 28689143]
[105]
Solcà M, Ronchi R, Bello-Ruiz J, et al. Heartbeat-enhanced immersive virtual reality to treat complex regional pain syndrome. Neurology 2018; 91(5): e479-89.
[http://dx.doi.org/10.1212/WNL.0000000000005905] [PMID: 29980635]
[106]
Buttery PC, Barker RA. Gene and cell-based therapies for Parkinson’s disease: where are we? Neurotherapeutics 2020; 17(4): 1539-62.
[http://dx.doi.org/10.1007/s13311-020-00940-4] [PMID: 33128174]
[107]
Chatterjee S, Sivanandam V, Wong KKM Jr. Adeno-associated virus and hematopoietic stem cells: The potential of adeno-associated virus hematopoietic stem cells in genetic medicines. Hum Gene Ther 2020; 31(9-10): 542-52.
[http://dx.doi.org/10.1089/hum.2020.049] [PMID: 32253938]
[108]
Hajba L, Guttman A. Recent advances in the analysis full/empty capsid ratio and genome integrity of adeno-associated virus (AAV) gene delivery vectors. Curr Mol Med 2021; 20(10): 806-13.
[http://dx.doi.org/10.2174/1566524020999200730181042] [PMID: 32748744]
[109]
Mingozzi F, Büning H. Adeno-associated viral vectors at the frontier between tolerance and immunity. Front Immunol 2015; 6: 120.
[http://dx.doi.org/10.3389/fimmu.2015.00120] [PMID: 25852689]
[110]
Li T, Gao T, Chen H, Pekker P, Menyhart A, Guttman A. Rapid determination of full and empty adeno-associated virus capsid ratio by capillary isoelectric focusing. Curr Mol Med 2021; 20(10): 814-20.
[http://dx.doi.org/10.2174/1566524020666200915105456] [PMID: 32933458]
[111]
Kaplitt MG, Feigin A, Tang C, et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: An open label, phase I trial. Lancet 2007; 369(9579): 2097-105.
[http://dx.doi.org/10.1016/S0140-6736(07)60982-9] [PMID: 17586305]
[112]
Feigin A, Kaplitt MG, Tang C, et al. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson’s disease. Proc Natl Acad Sci USA 2007; 104(49): 19559-64.
[http://dx.doi.org/10.1073/pnas.0706006104] [PMID: 18042721]
[113]
Eberling JL, Jagust WJ, Christine CW, et al. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology 2008; 70(21): 1980-3.
[http://dx.doi.org/10.1212/01.wnl.0000312381.29287.ff] [PMID: 18401019]
[114]
Christine CW, Starr PA, Larson PS, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 2009; 73(20): 1662-9.
[http://dx.doi.org/10.1212/WNL.0b013e3181c29356] [PMID: 19828868]
[115]
Marks WJ Jr, Ostrem JL, Verhagen L, et al. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2–neurturin) to patients with idiopathic Parkinson’s disease: An open-label, phase I trial. Lancet Neurol 2008; 7(5): 400-8.
[http://dx.doi.org/10.1016/S1474-4422(08)70065-6] [PMID: 18387850]
[116]
Marks WJ Jr, Bartus RT, Siffert J, et al. Gene delivery of AAV2-neurturin for Parkinson’s disease: A double-blind, randomised, controlled trial. Lancet Neurol 2010; 9(12): 1164-72.
[http://dx.doi.org/10.1016/S1474-4422(10)70254-4] [PMID: 20970382]
[117]
Bartus RT, Baumann TL, Siffert J, et al. Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology 2013; 80(18): 1698-701.
[http://dx.doi.org/10.1212/WNL.0b013e3182904faa] [PMID: 23576625]
[118]
Mata IF, Shi M, Agarwal P, Chung KA, Edwards KL, Factor SA, et al. SNCA variant associated with Parkinson disease and plasma alpha-synuclein level. Arch Neurol 2010; 67: 1350-6.
[119]
Cederfjäll E, Nilsson N, Sahin G, Chu Y, Nikitidou E, Björklund T, et al. Continuous DOPA synthesis from a single AAV: Dosing and efficacy in models of Parkinson’s disease. Sci Rep 2013; 3: 2157.
[http://dx.doi.org/10.1038/srep02157]
[120]
Kordower JH, Bjorklund A. Trophic factor gene therapy for Parkinson’s disease. Mov Disord 2013; 28(1): 96-109.
[http://dx.doi.org/10.1002/mds.25344] [PMID: 23390096]
[121]
Barker RA, Parmar M, Studer L, Takahashi J. Human trials of stem cell-derived dopamine neurons for Parkinson’s disease: Dawn of a new era. Cell Stem Cell 2017; 21(5): 569-73.
[http://dx.doi.org/10.1016/j.stem.2017.09.014] [PMID: 29100010]
[122]
Panova AV, Goliudsova DV, Kiselev SL. The prospect of pluripotent stem cells for diabetes mellitus treatment. World Personal Med 2017; 1(1): 13-7.
[http://dx.doi.org/10.14341/WJPM9297]
[123]
Zheng J, Jia Y, Liu S, Chi M, Cheng S, Gu Z. Molecular characterization and expression profiles of transcription factor Sox gene family in Culter alburnus. Gene Expr Patterns 2020; 36119112.
[http://dx.doi.org/10.1016/j.gep.2020.119112] [PMID: 32259660]
[124]
Grealish S, Diguet E, Kirkeby A, et al. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease. Cell Stem Cell 2014; 15(5): 653-65.
[http://dx.doi.org/10.1016/j.stem.2014.09.017] [PMID: 25517469]
[125]
Barker RA, de Beaufort I. Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain. Prog Neurobiol 2013; 110: 63-73.
[http://dx.doi.org/10.1016/j.pneurobio.2013.04.003] [PMID: 23665410]
[126]
Kikuchi T, Morizane A, Doi D, et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 2017; 548(7669): 592-6.
[http://dx.doi.org/10.1038/nature23664] [PMID: 28858313]
[127]
Deng XY, Wang H, Wang T, et al. Non-viral methods for generating integration-free, induced pluripotent stem cells. Curr Stem Cell Res Ther 2015; 10(2): 153-8.
[http://dx.doi.org/10.2174/1574888X09666140923101914] [PMID: 25248676]
[128]
Venkatesh K, Sen D. Mesenchymal stem cells as a source of dopaminergic neurons: A potential cell based therapy for Parkinson’s disease. Curr Stem Cell Res Ther 2017; 12(4): 326-47.
[http://dx.doi.org/10.2174/1574888X12666161114122059] [PMID: 27842480]
[129]
González C, Bonilla S, Isabel Flores A, Cano E, Liste I. An update on human stem cell-based therapy in Parkinson’s disease. Curr Stem Cell Res Ther 2016; 11(7): 561-8.
[http://dx.doi.org/10.2174/1574888X10666150531172612] [PMID: 26027681]
[130]
Harrell CR, Gazdic M, Fellabaum C, et al. Therapeutic potential of amniotic fluid derived mesenchymal stem cells based on their differentiation capacity and immunomodulatory properties. Curr Stem Cell Res Ther 2019; 14(4): 327-36.
[http://dx.doi.org/10.2174/1574888X14666190222201749] [PMID: 30806325]
[131]
Hallett PJ, Cooper O, Sadi D, Robertson H, Mendez I, Isacson O. Long-term health of dopaminergic neuron transplants in Parkinson’s disease patients. Cell Rep 2014; 7(6): 1755-61.
[http://dx.doi.org/10.1016/j.celrep.2014.05.027] [PMID: 24910427]
[132]
Björklund A, Dunnett SB, Brundin P, et al. Neural transplantation for the treatment of Parkinson’s disease. Lancet Neurol 2003; 2(7): 437-45.
[http://dx.doi.org/10.1016/S1474-4422(03)00442-3] [PMID: 12849125]
[133]
Lindvall O. Treatment of Parkinsons disease using cell transplantation. Philos Trans R Soc Lond B Biol Sci 2015; 370(1680): 20140370.
[134]
Herzog J, Fietzek U, Hamel W, et al. Most effective stimulation site in subthalamic deep brain stimulation for Parkinson’s disease. Mov Disord 2004; 19(9): 1050-4.
[http://dx.doi.org/10.1002/mds.20056] [PMID: 15372594]
[135]
Duker AP, Espay AJ. Surgical treatment of Parkinson disease: Past, present, and future. Neurol Clin 2013; 31(3): 799-808.
[http://dx.doi.org/10.1016/j.ncl.2013.03.007] [PMID: 23896506]
[136]
Nakamori M, Junn E, Mochizuki H, Mouradian MM. Nucleic acid–based therapeutics for Parkinson’s disease. Neurotherapeutics 2019; 16(2): 287-98.
[http://dx.doi.org/10.1007/s13311-019-00714-7] [PMID: 30756362]
[137]
Meister G, Landthaler M, Dorsett Y, Tuschl T. Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA 2004; 10(3): 544-50.
[http://dx.doi.org/10.1261/rna.5235104] [PMID: 14970398]
[138]
Maraganore DM. Rationale for therapeutic silencing of alpha-synuclein in Parkinson’s disease. J Mov Disord 2011; 4(1): 1-7.
[http://dx.doi.org/10.14802/jmd.11001] [PMID: 24868385]
[139]
Cookson MR. α-Synuclein and neuronal cell death Mol Neurodegener 2009; 4(1): 9.
[http://dx.doi.org/10.1186/1750-1326-4-9] [PMID: 19193223]
[140]
Kanagaraj N, Beiping H, Dheen ST, Tay SSW. Downregulation of miR-124 in MPTP-treated mouse model of Parkinson’s disease and MPP iodide-treated MN9D cells modulates the expression of the calpain/cdk5 pathway proteins. Neuroscience 2014; 272: 167-79.
[http://dx.doi.org/10.1016/j.neuroscience.2014.04.039] [PMID: 24792712]
[141]
Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord 2012; 18 (Suppl. 1): S210-2.
[http://dx.doi.org/10.1016/S1353-8020(11)70065-7] [PMID: 22166438]
[142]
Thome AD, Harms AS, Volpicelli-Daley LA, Standaert DG. Volpicelli-DaleyLA, Standaert DG. microRNA-155 regulates alpha-synuclein-induced inflammatory responses in models of Parkinson disease. J Neurosci 2016; 36(8): 2383-90.
[http://dx.doi.org/10.1523/JNEUROSCI.3900-15.2016] [PMID: 26911687]

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