The Past, Present, and Future of Parkinson's Disease Treatment
Abstract
Parkinson’s Disease was first introduced by James Parkinson in 1817. Since then, major strides have been made in the development of its treatment. Early treatments were dominated by traditional and complementary therapies, which were largely serendipitous and observation-based. Especially, the use of anticholinergics by Jean-Martin Charcot and his student Ordenstein prevailed in the late 20th century. Current drug-based therapies manifest in the form of levodopa accompanied by dopamine agonist, COMT inhibitor, or MAO-B inhibitor, for the purpose of reducing the levodopa-induced symptom fluctuation. In terms of surgical treatment, while ablative surgeries in the brain have been abandoned due to high mortality rate in the late 1900s, Deep Brain Stimulation in the subthalamic nucleus or internal globus pallidus has mostly replaced ablative surgeries since its introduction in 1987. Current research topics include non-dopaminergic agents for motor fluctuation reduction, transplantation of dopaminergic neurons, gene therapies using viral vectors, reduction of alpha-synuclein neurotoxicity, and neuroprotective therapies. Especially, due to the fact that the etiology of the disease is yet to be elucidated, neuroprotective therapies aimed at slowing or stopping disease progression are of particular interest. It is suggested that future research should aim towards clarifying the cause of the disease, for the development of a treatment that can permanently halt or reverse Parkinson’s Disease-related neurodegeneration.
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Singleton AB, Farrer MJ, Bonifati V. The genetics of Parkinson's disease: progress and therapeutic implications. Movement Disorders. 2013;28(1):14–23.
Parkinson, J. An Essay on the Shaking Palsy. London: Whittingham and Rowland for Sherwood, Needly, and Jones; 1817.
Salamon A, Zádori D, Szpisjak L, Klivényi P, Vécsei L. Neuroprotection in Parkinson’s disease: facts and hopes. Journal of Neural Transmission. 2019;127:821–9.
Goetz CG. The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies. Cold Spring Harbor Perspectives in Medicine. 2011;1(1).
Goetz CG, Bonduelle M, Gelfand T. Charcot: Constructing Neurology. New York: Oxford University Press; 1995.
Pahwa R, Lyons KE, Koller WC, editors. Therapy of Parkinson’s Disease. 3rd ed. New York: Marcel Dekker, Inc.; 2004.
Horsley V, Clarke RH. The structure and functions of the cerebellum examined by a new method. Brain. 1908;31(1):45–124.
Gracies J, Olanow CW. Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia: Lippincott Williams & Wilkins; 2002. Chapter 124, Current and Experimental Therapeutics of Parkinson's Disease; p. 1795-1816.
Scott RM, Brody JA, Cooper IS. The effect of thalamotomy on the progress of unilateral Parkinson's Disease. Journal of Neurosurgery. 1970;32(3):286–8.
del Rey NL, Quiroga-Varela A, Garbayo E, Carballo-Carbajal I, Fernández-Santiago R, Monje MH, et al. Advances in Parkinson’s Disease: 200 years later. Frontiers in Neuroanatomy. 2018;12:113.
Rascol O, Lozano A, Stern M, Poewe W. Milestones in Parkinson's disease therapeutics. Movement Disorders. 2011;26:1072–82.
Tolosa E, Martí MJ, Valldeoriola F, Molinuevo JL. History of levodopa and dopamine agonists in Parkinson’s disease treatment. Neurology. 1998:50(6 Suppl 6):S2-10; discussion S44-8.
Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Movement Disorders. 2001;16(3):448-58.
Bressman S, Saunders-Pullman R. When to start levodopa therapy for Parkinson’s Disease. New England Journal of Medicine. 2019;380:389-390
Olano CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications. The Lancet Neurology. 2006;5(8):677-687.
Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. The Lancet Neurology. 2014;13(2):141–9.
Lang AE, Rodriguez RL, Boyd JT, Chouinard S, Zadikoff C, Espay AJ, et al. Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials. Movement Disorders. 2016;31(4):538–46.
Olanow CW. A rationale for Dopamine Agonists as primary therapy for Parkinson’s Disease. The Canadian Journal of Neurological Sciences. 1992;19:108-112.
Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson's disease: an old drug still going strong. Clinical Interventions in Aging. 2010;5:229-238.
Parkinson Study Group CALM Cohort Investigators. Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease. Archives of Neurology. 2009;66(5):563-570.
Stibe CM, Lees AJ, Kempster PA, Stern GM. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet. 1988;1(8582):403-406.
Boyle A, Ondo W. Role of Apomorphine in the Treatment of Parkinson’s Disease. CNS Drugs. 2015;29: 83–89.
Parkinson Study Group. Entacapone improves motor fluctuations in levodopa- treated Parkinson's Disease patients. Annals of Neurology. 1997;42(5):747–755.
Rivest J, Barclay CL, Suchowersky O. COMT inhibitors in Parkinson’s Disease. The Canadian Journal of Neurological Sciences. 1999;26(Suppl 2): S34-38.
Goldenberg MM. Medical management of Parkinson's disease. P&T: a peer-reviewed journal for formulary management. 2008;33(10):590-606.
Watkins P. COMT inhibitors and liver toxicity. Neurology. 2000;55(11 Suppl 4):S51-S56.
Stocchi F, Rascol O, Kieburtz K, Poewe W, Jankovic J, Tolosa E, et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: The STRIDE‐PD study. Annals of Neurology. 2010;68:18-27.
Langston JW. The MPTP Story. Journal of Parkinson’s Disease. 2017;7(s1):S11-S19.
Shoulson I. DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism. Annals of Neurology. 1998;44(3 Suppl 1):S160-6.
Rascol O, Brooks DJ, Melamed E, Oerte W, Poewe W, Stocchi F, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005;365(9463):947-954.
Jenner P, Langston JW. Explaining ADAGIO: a critical review of the biological basis for the clinical effects of rasagiline. Movement Disorders. 2011;26(13):2316-2323.
Jankovic J, Poewe W. Therapies in Parkinson’s Disease. Current Opinion in Neurology. 2012;25(4):433–447.
Bergman H, Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science. 1990;249(4975):1436-1438.
DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends in Neurosciences. 1990;13(7):281-285.
Vitek JL, Bakay RA, Freeman A, Evatt M, Green J, McDonald W, et al. Randomized trial of pallidotomy versus medical therapy for Parkinson's disease. Annals of Neurology. 2003;53(5):558-69.
de Bie RM, de Haan RJ, Schuurman PR, Esselink RA, Bosch DA, Speelman JD. Morbidity and mortality following pallidotomy in Parkinson's disease: a systematic review. Neurology. 2002;58(7):1008-12.
Guridi J, Herrero MT, Luquin R, Guillen J, Obeso JA. Subthalamotomy improves MPTP-induced parkinsonism in monkeys. Stereotactic and Functional Neurosurgery. 1994;62(1-4):98-102.
Alvarez L, Macias R, Pavón N, López G, Rodríguez-Oroz MC, Rodríguez R, et al. Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months. Journal of neurology, neurosurgery, and psychiatry. 2009;80(9):979-85.
Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Applied Neurophysiology. 1987;50(1-6):344-346.
Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K. A randomized trial of Deep-Brain Stimulation for Parkinson’s Disease. The New England Journal of Medicine. 2006;355:896-908.
Herrington TM, Cheng JJ, Eskandar EN. Mechanisms of deep brain stimulation. Journal of Neurophysiology. 2016;115(1):19-38.
Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63-73.
Rodriguez-Oroz MC, Moro E, Krack P. Long-term outcomes of surgical therapies for Parkinson's disease. Movement Disorders. 2012;27(14):1718-1728.
Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s Disease. The New England Journal of Medicine. 2010;362:2077-2091.
Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, et al. Practice Parameter: Treatment of Parkinson Disease with Motor Fluctuations and Dyskinesia (an Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):983–995.
Martinez-Fernandez R, Pelissier P, Quesada JL, Klinger H, Lhommée E, Schmitt E, et al. Postoperative apathy can neutralise benefits in quality of life after subthalamic stimulation for Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry. 2016;87(3):311-8.
Thobois S, Ardouin C, Lhommée E, Klinger H, Lagrange C, Xie J, et al. Non-motor dopamine withdrawal syndrome after surgery for Parkinson's disease: predictors and underlying mesolimbic denervation. Brain. 2010;133(Pt 4):1111-27.
Voon V, Krack P, Lang AE, Lozano AM, Dujardin K, Schüpbach M, et al. A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson's disease. Brain. 2008;131(Pt 10):2720-8.
Kedia S, Moro E, Tagliati M, Lang AE, Kumar R. Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease. Neurology. 2004;63(12):2410-12.
Feng X, Greenwald B, Rabitz H, Shea-Brown E, Kosut R. Toward closed-loop optimization of deep brain stimulation for Parkinson's disease: concepts and lessons from a computational model. Journal of Neural Engineering. 2007;4(2).
Lee DJ, Lozano CS, Dallapiazza RF, Lozano AM. Current and future directions of deep brain stimulation for neurological and psychiatric disorders. Journal of Neurosurgery. 2019;131(2):333-656.
Snow BJ, Macdonald L, Mcauley D, Wallis W. The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study. Clinical Neuropharmacology. 2000;23(2):82-85.
Metman LV, Del Dotto P, LePoole K, Konitsiotis S, Fang J, Chase TN. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Archives of Neurology. 1999;56(11):1383-1386.
Olanow CW, Jankovic J. Neuroprotective therapy in Parkinson's disease and motor complications: A search for a pathogenesis‐targeted, disease‐modifying strategy. Movement Disorders. 2005;20:S3-S10.
Merims D, Ziv I, Djaldetti R, Melamed E. Riluzole for levodopa-induced dyskinesias in advanced Parkinson’s disease. The Lancet. 1999;353(9166):1764-1765.
Obinu MC, Reibaud M, Blanchard V, Moussaoui S, Imperato A. Neuroprotective effect of riluzole in a primate model of Parkinson's disease: Behavioral and histological evidence. Movement Disorders. 2002;17:13-19.
Jankovic J, Hunter C. A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson's disease. Parkinsonism & Related Disorders. 2002;8(4):271-6.
Jenner P, Mori A, Hauser R, Morelli M, Fredholm BB, Chen JF. Adenosine, adenosine A2A antagonists, and Parkinson's disease. Parkinsonism & Related Disorders. 2009;15(6):406-13.
Franco R, Navarro G. Adenosine A2A receptor antagonists in neurodegenerative diseases: Huge potential and huge challenges. Frontiers in Psychiatry. 2018;9:68.
Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Annals of Neurology. 2003;54(3):403-14.
Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z, et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature. 2011;480(7378):547-51.
Stoker TB, Torsney KM, Barker RA. Emerging treatment approaches for Parkinson’s Disease. Frontiers in Neuroscience. 2018;12:693.
Chen W, Huang Q, Ma S, Li M. Progress in dopaminergic cell replacement and regenerative strategies for Parkinson's Disease. ACS Chemical Neuroscience. 2019;10(2):839-851.
Christine CW, Bankiewicz KS, Van Laar AD, Richardson RM, Ravina B, Kells AP, et al. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease. Annals of Neurology. 2019;85(5):704-714.
Muramatsu S, Fujimoto K, Kato S, Mizukami H, Asari S, Ikeguchi K, et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson's disease. Molecular therapy : the journal of the American Society of Gene Therapy. 2010;18(9):1731-5.
Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology. 2009;73(20):1662-9.
Palfi S, Gurruchaga JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC, et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial. Lancet. 2014;383(9923):1138-46.
LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, et al. AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial. The Lancet Neurology. 2011;10(4):309-19.
Heiss JD, Lungu C, Hammoud DA, Herscovitch P, Ehrlich DJ, Argersinger DP, et al. Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson's disease. Movement Disorders. 2019;34(7):1073-1078.
Marks Jr WJ, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, et al. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. The Lancet Neurology. 2010;9(12):1164-72.
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease. Science. 1997:276(5321);2045-7.
Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(11):6469-6473.
Manfredsson F, Lewin A, Mandel R. RNA knockdown as a potential therapeutic strategy in Parkinson's disease. Gene Therapy. 2006;13:517–524.
Mittal S, Bjørnevik K, Im DS, Flierl A, Don X, Locascio JJ, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science. 2017;357(6354):891-8.
Jin H, Kanthasamy A, Ghosh A, Yang Y, Anantharam V, Kanthasamy AG. α-Synuclein negatively regulates protein kinase Cδ expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity. The Journal of Neuroscience. 2011;31(6):2035-2051.
Rodriguez-Araujo G, Nakagami H, Takami Y, Katsuya T, Akasaka H, Saitoh S, et al. Low alpha-synuclein levels in the blood are associated with insulin resistance. Scientific Reports. 2015;5:12081.
Peng X, Tehranian R, Dietrich P, Stefanis L, Perez RG. Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. Journal of cell science. 2005;118(Pt 15):3523-3530.
Park SM, Jung HY, Kim TD, Park JH, Yang CH, Kim J. Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of alpha-synuclein, a molecular chaperone. The Journal of Biological Chemistry. 2002;277(32):28512-28520.
Zhu M, Qin ZJ, Hu D, Munishkina LA, Fink AL. Alpha-synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles. Biochemistry. 2006;45(26):8135-8142.
Gorbatyuk OS, Li S, Nash K, et al. In vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration. Molecular therapy : the journal of the American Society of Gene Therapy. 2010;18(8):1450-1457.
Study Assessing Tolerability and Safety of AFFITOPE® PD03A in Patients With Early Parkinson's Disease (AFF011). ClinicalTrials.gov Identifier: NCT02267434. 2014 [updated 2016 Oct 31; cited 2020 Aug 13]. Available from: https://clinicaltrials.gov/ct2/show/NCT02267434.
Schenk DB, Koller M, Ness DK, Griffith SG, Grundman M, Zago W, et al. First‐in‐human assessment of PRX002, an anti–α‐synuclein monoclonal antibody, in healthy volunteers. Movement Disorders. 2017;32:211-218.
Cullen V, Sardi SP, Ng J, Xu YH, Sun Y, Tomlinson JJ, et al. Acid β‐glucosidase mutants linked to gaucher disease, parkinson disease, and lewy body dementia alter α‐synuclein processing. Annals of Neurology. 2011;69:940-953.
Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease. Journal of Neuroinflammation. 2008;5:19.
Kim S, Moon M, Park S. Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease. Journal of Endocrinology. 2009;202(3):431-439.
Dilan A, Richard W, Patrik B, Thomas F. Is Exenatide a treatment for Parkinson’s disease? Journal of Parkinson’s Disease. 2017;7(3):451-8.
Nuñez MT, Chana-Cuevas P. New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases. Pharmaceuticals (Basel, Switzerland). 2018;11(4):109.
Kalia, L.V., Kalia, S.K. and Lang, A.E. (2015), Disease‐modifying strategies for Parkinson's disease. Movement Disorders. 30(11):1442-1450.
The Parkinson Study Group SURE-PD Investigators. Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical Trial. JAMA Neurology. 2014;71(2):141–150.
DOI: https://doi.org/10.23954/osj.v5i4.2622
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