Journal Home > Volume 3 , Issue 1

Parkinson’s disease (PD) is one of the common neurodegenerative diseases. Besides the symptomatic therapies, the increasing numbers of neurorestorative therapies have shown the potential therapeutic value of reversing the neurodegenerative process and improving the patient’s quality of life. Currrently available novel clinical neurorestorative strategies include pharmacological managements (glial cell-line derived neurotrophic factor, selegiline, recombinant human erythropoietin), neuromodulation intervention (deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation), tissue and cell transplantation (fetal ventral mesencephalic tissue, sympathetic neurons, carotid body cells, bone marrow stromal cells, retinal pigment epithelium cells), gene therapy, and neurorehabilitative therapy. Herein, we briefly review the progress in this field and describe the neurorestorative mechanisms of the above-mentioned therapies for PD.


menu
Abstract
Full text
Outline
About this article

Clinical neurorestorative progress in Parkinson’s disease

Show Author's information Lin Chen1,2( )Hongyun Huang3,4,5Wei-Ming Duan6( )Gengsheng Mao3
Department of Neurosurgery, Yuquan Hospital, Tsinghua University,
Department of Neurosurgery, Medical Center, Tsinghua University,
Department of Neurosurgery, General Hospital of Chinese People’s Armed Police Forces,
Center of Cell Research, Beijing Rehabilitation Hospital of Capital Medical University,
Beijing Hongtianji Neuroscience Academy,
Department of Anatomy, Capital Medical University, Beijing, People’s Republic of China

Abstract

Parkinson’s disease (PD) is one of the common neurodegenerative diseases. Besides the symptomatic therapies, the increasing numbers of neurorestorative therapies have shown the potential therapeutic value of reversing the neurodegenerative process and improving the patient’s quality of life. Currrently available novel clinical neurorestorative strategies include pharmacological managements (glial cell-line derived neurotrophic factor, selegiline, recombinant human erythropoietin), neuromodulation intervention (deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation), tissue and cell transplantation (fetal ventral mesencephalic tissue, sympathetic neurons, carotid body cells, bone marrow stromal cells, retinal pigment epithelium cells), gene therapy, and neurorehabilitative therapy. Herein, we briefly review the progress in this field and describe the neurorestorative mechanisms of the above-mentioned therapies for PD.

Keywords: Parkinson’s disease, cell transplantation, clinical study, neuromodulation, neurorestorative treatment

References(85)

1.
Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatr. 2008;79:368–376.
2.
Yao SC, Hart AD, Terzella MJ. An evidence-based osteopathic approach to Parkinson disease. Osteopath Fam Phys. 2013;5:96–101.
3.
de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5:525–535.
4.
Davie CA. A review of Parkinson’s disease. Br Med Bull. 2008;86:109–127.
5.
Dickson DV. Neuropathology of movement disorders. In: Tolosa E, Jankovic JJ, editors. Parkinson’s Disease and Movement Disorders. Hagerstown, MD: Lippincott Williams & Wilkins; 2007:271–283.
6.
National Collaborating Centre for Chronic Conditions (NCCCC). Parkinson’s Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care. London: Royal College of Physicians; 2006:59–100.
7.
Bronstein JM, Tagliati M, Alterman RL, et al. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Arch Neurol. 2011;68:165.
8.
Slevin JT, Gash DM, Smith CD, et al. Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal. J Neurosurg. 2007;106:614–620.
9.
Pålhagen S, Heinonen E, Hägglund J, et al; Swedish Parkinson Study Group. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology. 2006;66:1200–1206.
10.
Jang W, Park J, Shin KJ, et al. Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson’s disease. J Neurol Sci. 2014;337:47–54.
11.
Bekhtereva NP, Grachev KV, Orlova AN, Iatsuk SL. Utilization of multiple electrodes implanted in the subcortical structure of the human brain for the treatment of hyperkinesis. Zh Nevropatol Psikhiatr Im S S Korsakova. 1963;63:3–8.
12.
National Collaborating Centre for Chronic Conditions (NCCCC). Parkinson’s Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care. London: Royal College of Physicians; 2006:101–111.
13.
Tao Y, Liang G. Effect of subthalamic nuclei electrical stimulation in the treatment of Parkinson’s disease. Cell Biochem Biophys. 2015;71(1):113–117.
14.
Bril’ EV, Tomskiĭ AA, Gamaleia AA, et al. A comparative study of the efficacy of deep brain stimulation of the subthalamic nucleus and pharmacological treatment in advanced Parkinson’s disease. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114:55–61.
15.
Cordeiro KK, Cordeiro JG, Furlanetti LL, et al. Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonianrats. Eur J Neurosci. 2014;39:1474–1484.
16.
Koch G, Brusa L, Caltagirone C, et al. rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease. Neurology. 2005;65:623–625.
17.
Elahi B, Elahi B, Chen R. Effect of transcranial magnetic stimulation on Parkinson motor function – systematic review of controlled clinical trials. Mov Disord. 2009;24:357–363.
18.
von Papen M, Fisse M, Sarfeld AS, Fink GR, Nowak DA. The effects of 1 Hz rTMS preconditioned by tDCS on gait kinematics in Parkinson’s disease. J Neural Transm. 2014;121:743–754.
19.
Kaski D, Dominguez R, Allum J, Islam A, Bronstein A. Combining physical training with transcranial direct current stimulation to improve gait in Parkinson’s disease: a pilot randomized controlled study. Clin Rehabil. 2014;28(11):1115–1124.
20.
Kaski D, Allum JH, Bronstein AM, Dominguez RO. Applying anodal tDCS during tango dancing in a patient with Parkinson’s disease. Neurosci Lett. 2014;568:39–43.
21.
Spagnolo F, Volonté MA, Fichera M, et al. Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson’s disease: an open label, pilot study. Brain Stimul. 2014;7:297–300.
22.
Fry FJ, Ades HW, Fry WJ. Production of reversible changes in the central nervous system by ultrasound. Science. 1958;127:83–84.
23.
Huber PE, Rastert R, Simiantonakis I, et al. Magnetic resonance-guided therapy with focused ultrasound. Non-invasive surgery of breast carcinoma? Radiologe. 2001;41:173–180.
24.
Schlesinger D, Benedict S, Diederich C, Gedroyc W, Klibanov A, Larner J. MR-guided focused ultrasound surgery, present and future. Med Phys. 2013;40:080901.
25.
Dobrakowski PP, Machowska-Majchrzak AK, Labuz-Roszak B, Majchrzak KG, Kluczewska E, Pierzchała KB. MR-guided focused ultrasound: a new generation treatment of Parkinson’s disease, essential tremor and neuropathic pain. Interv Neuroradiol. 2014;20:275–282.
26.
Sturkenboom IH, Graff MJ, Hendriks JC, et al; OTiP Study Group. Efficacy of occupational therapy for patients with Parkinson’s disease: a randomised controlled trial. Lancet Neurol. 2014;13:557–566.
27.
Foster ER, Bedekar M, Tickle-Degnen L. Systematic review of the effectiveness of occupational therapy-related interventions for people with Parkinson’s disease. Am J Occup Ther. 2014;68:39–49.
28.
Thaut MH, McIntosh GC, Rice RR, Miller RA, Rathbun J, Brault JM. Rhythmic auditory stimulation in gait training for Parkinson’s disease patients. Mov Disord. 1996;11(2):193–200.
29.
Ellis T, de Goede CJ, Feldman RG, Wolters EC, Kwakkel G, Wagenaar RC. Efficacy of a physical therapy program in patients with Parkinson’s disease: a randomized controlled trial. Arch Phys Med Rehabil. 2005;86:626–632.
30.
Frazzitta G, Maestri R, Bertotti G, et al. Intensive rehabilitation treatment in early Parkinson’s disease: a randomized pilot study with a 2-year follow-up. Neurorehabil Neural Repair. 2015;29(2):123–131.
31.
Athukorala RP, Jones RD, Sella O, Huckabee ML. Skill training for swallowing rehabilitation in patients with Parkinson’s disease. Arch Phys Med Rehabil. 2014;95:1374–1382.
32.
Ploughman M, Shears J, Harris C, et al. Effectiveness of a novel community exercise transition program for people with moderate to severe neurological disabilities. NeuroRehabilitation. 2014;35(1):105–112.
33.
Backlund EO, Granberg PO, Hamberger B, et al. Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J Neurosurg. 1985;62:169–173.
34.
Barker RA, Barrett J, Mason SL, Björklund A. Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson’s disease. Lancet Neurol. 2013;12:84–91.
35.
Dunnett SB. Neural tissue transplantation, repair, and rehabilitation. Handb Clin Neurol. 2013;110:43–59.
36.
Parish CL, Thompson LH. Modulating Wnt signaling to improve cell replacement therapy for Parkinson’s disease. J Mol Cell Biol. 2014;6:54–63.
37.
Thompson LH, Parish CL. Transplantation of fetal midbrain dopamine progenitors into a rodent model of Parkinson’s disease. Methods Mol Biol. 2013;1059:169–180.
38.
Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001;344:710–719.
39.
Olanow CW, Goetz CG, Kordower JH, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol. 2003;54(3):403–414.
40.
Ma Y, Tang C, Chaly T, et al. Dopamine cell implantation in Parkinson’s disease: long-term clinical and (18)F-FDOPA PET outcomes. J Nucl Med. 2010;51(1):7–15.
41.
Kefalopoulou Z, Politis M, Piccini P, et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol. 2014;71:83–87.
42.
Nakao N, Kakishita K, Uematsu Y, et al. Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease. J Neurosurg. 2001;95:275–284.
43.
Mínguez-Castellanos A, Escamilla-Sevilla F, Hotton GR, et al. Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study. J Neurol Neurosurg Psychiatry. 2007;78(8):825–831.
44.
Venkataramana NK, Kumar SK, Balaraju S, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res. 2010;155:62–70.
45.
Venkataramana NK, Pal R, Rao SA, et al. Bilateral transplantation of allogenic adult human bone marrow-derived mesenchymal stem cells into the subventricular zone of Parkinson’s disease: a pilot clinical study. Stem Cells Int. 2012;2012:931902.
46.
Xue Y, Li X, Pang S, et al. Efficacy and safety of computer-assisted stereotactic transplantation of human retinal pigment epithelium cells in the treatment of Parkinson disease. J Comput Assist Tomogr. 2013;37:333–337.
47.
Yin F, Tian ZM, Liu S, et al. Transplantation of human retinal pigment epithelium cells in the treatment for Parkinson disease. CNS Neurosci Ther. 2012;18:1012–1020.
48.
Watts RL, Raiser CD, Stover NP, et al. Stereotaxicintrastriatalimplantation of human retinal pigment epithelial (hRPE) cellsattached to gelatinmicrocarriers: a potential new cell therapy for Parkinson’s disease. J Neural Transm Suppl. 2003;65:215–227.
49.
Gross RE, Watts RL, Hauser RA, et al; Spheramine Investigational Group. Intrastriatal transplantation of microcarrier-bound human retinal pigment epithelial cells versus sham surgery in patients with advanced Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2011;10:509–519.
50.
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;7:1755–1761.
51.
Bartus RT, Weinberg MS, Samulski RJ. Parkinson’s disease gene therapy: success by design meets failure by efficacy. Mol Ther. 2014;22:487–497.
52.
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;369:2097–2105.
53.
Eberling JL, Jagust WJ, Christine CW, et al. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology. 2008;70:1980–1983.
54.
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):400–408.
55.
Bartus RT, Baumann TL, Siffert J, et al. Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology. 2013;80:1698–1701.
56.
Perlow MJ, Freed WJ, Hoffer BJ, Seiger A, Olson L, Wyatt RJ. Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science. 1979;204:643–647.
57.
Rath A, Klein A, Papazoglou A, et al. Survival and functional restoration of human fetal ventral mesencephalon following transplantation in a rat model of Parkinson’s disease. Cell Transplant. 2013;22:1281–1293.
58.
Hansen JT, Bing GY, Notter MF, Gash DM. Paraneuronal grafts in unilateral 6-hydroxydopamine-lesioned rats: morphological aspects of adrenal chromaffin and carotid body glomus cell implants. Prog Brain Res. 1988;78:507–511.
59.
Doudet DJ, Cornfeldt ML, Honey CR, Schweikert AW, Allen RC. PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson’s disease. Exp Neurol. 2004;189:361–368.
60.
Schwarz EJ, Alexander GM, Prockop DJ, Azizi SA. Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease. Hum Gene Ther. 1999;10:2539–2549.
61.
Wang Y, Yang J, Li H, et al. Hypoxia promotes dopaminergic differentiation of mesenchymal stem cells and shows benefits for transplantation in a rat model of Parkinson’s disease. PLoS One. 2013;8:e54296.
62.
Campeau L, Soler R, Sittadjody S, et al. Effects of allogeneic bone marrow derived mesenchymal stromal cell therapy on voiding function in a rat model of Parkinson disease. J Urol. 2014;191:850–859.
63.
Soler R, Füllhase C, Hanson A, Campeau L, Santos C, Andersson KE. Stem cell therapy ameliorates bladder dysfunction in an animal model of Parkinson disease. J Urol. 2012;187:1491–1497.
64.
Weiss ML, Medicetty S, Bledsoe AR, et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells. 2006;24:781–792.
65.
Xiong N, Cao X, Zhang Z, et al. Long-term efficacy and safety of human umbilical cord mesenchymal stromal cells in rotenone-induced hemiparkinsonian rats. Biol Blood Marrow Transplant. 2010;16:1519–1529.
66.
Mathieu P, Roca V, Gamba C, Del Pozo A, Pitossi F. Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an immunocompetent animal model of Parkinson’s disease. J Neuroimmunol. 2012;246:43–50.
67.
Kang EJ, Lee YH, Kim MJ, et al. Transplantation of porcine umbilical cord matrix mesenchymal stem cells in a mouse model of Parkinson’s disease. J Tissue Eng Regen Med. 2013;7:169–182.
68.
Janowski M, Date I. Systemic neurotransplantation – a problem-oriented systematic review. Rev Neurosci. 2009;20:39–60.
69.
Abo-Grisha N, Essawy S, Abo-Elmatty DM, Abdel-Hady Z. Effects of intravenous human umbilical cord blood CD34+ stem cell therapy versus levodopa in experimentally induced Parkinsonism in mice. Arch Med Sci. 2013;9:1138–1151.
70.
Arnhold S, Lenartz D, Kruttwig K, et al. Differentiation of green fluorescent protein-labeled embryonic stem cell-derived neural precursor cells into Thy-1-positive neurons and glia after transplantation into adult rat striatum. J Neurosurg. 2000;93:1026–1032.
71.
Bjorklund LM, Sánchez-Pernaute R, Chung S, et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A. 2002;99:2344–2349.
72.
Ziavra D, Makri G, Giompres P, et al. Neural stem cells transplanted in a mouse model of Parkinson’s disease differentiate to neuronal phenotypes and reduce rotational deficit. CNS Neurol Disord Drug Targets. 2012;11:829–835.
73.
Proschel C, Stripay JL, Shih CH, Munger JC, Noble MD. Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons. EMBO Mol Med. 2014;6:504–518.
74.
Agrawal AK, Shukla S, Chaturvedi RK, et al. Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson’s disease: a cotransplantation approach with fetal ventral mesencephalic cells. Neurobiol Dis. 2004;16:516–526.
75.
Johansson S, Lee IH, Olson L, Spenger C. Olfactory ensheathing glial co-grafts improve functional recovery in rats with 6-OHDA lesions. Brain. 2005;128:2961–2976.
76.
Shukla S, Chaturvedi RK, Seth K, Roy NS, Agrawal AK. Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonianrats. J Neurochem. 2009;109:436–451.
77.
Feng L, Meng H, Wu F, et al. Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC12 cells through modulation of intrinsic apoptotic pathways. Int J Dev Neurosci. 2008;26:323–329.
78.
Meissner W, Harnack D, Paul G, et al. Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats. Neurosci Lett. 2002;328:105–108.
79.
Meissner W, Reum T, Paul G, et al. Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats. Neurosci Lett. 2001;303:165–168.
80.
Lortet S, Lacombe E, Boulanger N, et al. Striatal molecular signature of subchronic subthalamic nucleus high frequency stimulation in parkinsonian rat. PLoS One. 2013;8:e60447.
81.
Al-Jarrah M, Jamous M, Al Zailaey K, Bweir SO. Endurance exercise training promotes angiogenesis in the brain of chronic/progressive mouse model of Parkinson’s disease. NeuroRehabilitation. 2010;26:369–373.
82.
Al-Jarrah M, Jamous M. Effect of endurance exercise training on the expression of GFAP, S100B, and NSE in the striatum of chronic/progressive mouse model of Parkinson’s disease. NeuroRehabilitation. 2011;28:359–363.
83.
Al-Jarrah M, Obaidat H, Bataineh Z, Walton L, Al-Khateeb A. Endurance exercise training protects against the upregulation of nitric oxide in the striatum of MPTP/probenecid mouse model of Parkinson’s disease. NeuroRehabilitation. 2013;32:141–147.
84.
Wang Z, Myers KG, Guo Y, et al. Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism. PLoS One. 2013;8:e80058.
85.
Zhao L, He LX, Huang SN, et al. Protection of vibration training on dopamine neurons and up-regulation of brain-derived neurotrophic factor in a MPTP mouse model of Parkinson’s disease. Physiol Res. 2014;63:649–657.
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Published: 30 June 2015
Issue date: December 2015

Copyright

© 2015 The Author(s).

Acknowledgements

We thank Ms Lu Zheng for preparing this manuscript.

Rights and permissions

© 2015 Chen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Return