Gene Therapy in the Management of Parkinson’s Disease: Potential of GDNF as a Promising Therapeutic Strategy

Author(s): Tapan Behl*, Ishnoor Kaur, Arun Kumar, Vineet Mehta, Gokhan Zengin, Sandeep Arora

Journal Name: Current Gene Therapy

Volume 20 , Issue 3 , 2020


  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

The limitations of conventional treatment therapies in Parkinson’s disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates on the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and the loss of dopaminergic neurons in Parkinson’s disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors leads to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson’s disease, via its association with the essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of routine treatment therapy for patients.

Keywords: Neurodegenerative disorder, dopaminergic neuronal regeneration, subthalamic nucleus neurons, viral vector, fetal ventral mesencephalon, glial cell-line derived neurotrophic factor, ret receptor.

[1]
Schneider AJ, Friedmann T. The scientific basis for gene therapy. A new concept in medicine. Adv Genet 2006; 51.
[http://dx.doi.org/10.1016/S0065-2660(06)51002-8]
[2]
Ma CC, Wang ZL, Xu T, He ZY, Wei YQ. The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnol Adv 2020; 40 107502
[http://dx.doi.org/10.1016/j.biotechadv.2019.107502] [PMID: 31887345]
[4]
FDA; Cellular & gene therapy products 2019. Available from. https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/
[5]
Friedmann T. Clinical gene therapy: lessons from the ether dome. Mol Ther 2004; 10(2): 205-6.
[http://dx.doi.org/10.1016/j.ymthe.2004.07.009] [PMID: 15294165]
[6]
Stein CA, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Mol Ther 2017; 25(5): 1069-75.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.023] [PMID: 28366767]
[7]
Guo W, Song H. Development of gene therapeutics for head and neck cancer in China: from bench to bedside. Hum Gene Ther 2018; 29(2): 180-7.
[http://dx.doi.org/10.1089/hum.2017.230] [PMID: 29334764]
[8]
Liang M. Oncorine, the world first oncolytic virus medicine and its update in China. Curr Cancer Drug Targets 2018; 18(2): 171-6.
[http://dx.doi.org/10.2174/1568009618666171129221503] [PMID: 29189159]
[9]
Kim S, Federman N, Gordon EM, Hall FL, Chawla SP. Rexin-G®, a tumor-targeted retro vector for malignant peripheral nerve sheath tumor: a case report. Mol Clin Oncol 6(6): 861-5..
[http://dx.doi.org/10.3892/mco.2017.1231] [PMID: 28588778]
[10]
Deev R, Plaksa I, Bozo I, et al. Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication. Ther Adv Cardiovasc Dis 2018; 12(9): 237-46.
[http://dx.doi.org/10.1177/1753944718786926] [PMID: 29996720]
[11]
Ylä-Herttuala S. Endgame: glybera finally recommended for approval as the first gene therapy drug in the European union. Mol Ther 2012; 20(10): 1831-2.
[http://dx.doi.org/10.1038/mt.2012.194] [PMID: 23023051]
[12]
Goswami R, Subramanian G, Silayeva L, et al. Gene therapy leaves a vicious cycle. Front Oncol 2019; 9: 297.
[http://dx.doi.org/10.3389/fonc.2019.00297] [PMID: 31069169]
[13]
Naldini L. Gene therapy returns to centre stage. Nature 2015; 526(7573): 351-60.
[http://dx.doi.org/10.1038/nature15818] [PMID: 26469046]
[14]
Farkas AM, Mariz S, Stoyanova-Beninska V, et al. Advanced therapy medicinal products\ for rare diseases: state of play of incentives supporting development in Europe. Front Med (Lausanne) 2017; 4: 53.
[http://dx.doi.org/10.3389/fmed.2017.00053] [PMID: 28560211]
[15]
Hoggatt J. Gene therapy for “Bubble Boy” disease. Cell 2016; 166(2): 263.
[http://dx.doi.org/10.1016/j.cell.2016.06.049] [PMID: 27419862]
[16]
Ottesen EW. ISS-N1 makes the first FDA-approved drug for Spinal Muscular Atrophy. Transl Neurosci 2017; 8: 1-6.
[http://dx.doi.org/10.1515/tnsci-2017-0001] [PMID: 28400976]
[17]
Korinthenberg R. A new era in the management of Duchenne muscular dystrophy. Dev Med Child Neurol 2019; 61(3): 292-7.
[http://dx.doi.org/10.1111/dmcn.14129] [PMID: 30556126]
[18]
Morrison C. Fresh from the biotech pipeline-2017. Nat Biotechnol 2018; 36: 131-6.
[http://dx.doi.org/10.1038/nbt.4068] [PMID: 29355851]
[19]
Schuster SJ, Bishop MR, Tam CS, et al. JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2019; 380(1): 45-56.
[http://dx.doi.org/10.1056/NEJMoa1804980] [PMID: 30501490]
[20]
Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol 2019; 20(1): 31-42.
[http://dx.doi.org/10.1016/S1470-2045(18)30864-7] [PMID: 30518502]
[21]
Dias MF, Joo K, Kemp JA, et al. Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives. Prog Retin Eye Res 2018; 63: 107-31.
[http://dx.doi.org/10.1016/j.preteyeres.2017.10.004] [PMID: 29097191]
[22]
Evans CH, Ghivizzani SC, Robbins PD. Arthritis gene therapy approved in Korea. J Am Acad Orthop Surg 2018; 26(2): e36-8.
[http://dx.doi.org/10.5435/JAAOS-D-17-00695] [PMID: 29303924]
[23]
Evans CH, Ghivizzani SC, Robbins PD. Arthritis gene therapy is becoming a reality. Nat Rev Rheumatol 2018; 14(7): 381-2.
[http://dx.doi.org/10.1038/s41584-018-0009-5] [PMID: 29743627]
[24]
Chakradhar S. Treatments that made headlines in 2018. Nat Med 2018; 24(12): 1785-7.
[http://dx.doi.org/10.1038/s41591-018-0292-3] [PMID: 30523326]
[25]
Hoy SM. Onasemnogene Abeparvovec: first global approval. Drugs 2019; 79(11): 1255-62.
[http://dx.doi.org/10.1007/s40265-019-01162-5] [PMID: 31270752]
[26]
Suda H, Murakami A, Kaga T, Tomioka H, Morishita R. Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther 2014; 12(10): 1145-56.
[http://dx.doi.org/10.1586/14779072.2014.955850] [PMID: 25190335]
[27]
Paik J, Duggan S. Volanesorsen: first global approval. Drugs 2019; 79(12): 1349-54.
[http://dx.doi.org/10.1007/s40265-019-01168-z] [PMID: 31301033]
[28]
E.M.A. Zynteglo. autologous CD34+ cells encoding βA-T87Qglobin gene 2019. Available from. https://www.ema.europa.eu/en/medicines/human/EPAR/zynteglo
[29]
Warrington KH Jr, Herzog RW. Treatment of human disease by adeno-associated viral gene transfer. Hum Genet 2006; 119(6): 571-603.
[http://dx.doi.org/10.1007/s00439-006-0165-6] [PMID: 16612615]
[30]
Chen W, Hu Y, Ju D. Gene therapy for neurodegenerative disorders:advances, insights and prospects. Acta Pharm Sin B 2020; 10(8): 1347-59.
[http://dx.doi.org/10.1016/j.apsb.2020.01.015]
[31]
Hudry E, Vandenberghe LH. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron 2019; 101(5): 839-62.
[http://dx.doi.org/10.1016/j.neuron.2019.02.017] [PMID: 30844402]
[32]
Man JHK, Groenink L, Caiazzo M. Cell reprogramming approaches in gene- and cell based therapies for Parkinson’s disease. Corel 2018; 286: 114-24.
[http://dx.doi.org/10.1016/j.jconrel.2018.07.017]
[33]
Bartus RT, Weinberg MS, Samulski RJ. Parkinson’s disease gene therapy: success by design meets failure by efficacy. Mol Ther 2014; 22(3): 487-97.
[http://dx.doi.org/10.1038/mt.2013.281] [PMID: 24356252]
[34]
Staudt MD, Di Sebastiano AR, Xu H, et al. Advances in neurotrophic factor and cell-based therapies for Parkinson’s disease: a mini-review. Gerontology 2016; 62(3): 371-80.
[http://dx.doi.org/10.1159/000438701] [PMID: 26330171]
[35]
de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol 2006; 5(6): 525-35.
[http://dx.doi.org/10.1016/S1474-4422(06)70471-9] [PMID: 16713924]
[36]
Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 1991; 114(Pt 5): 2283-301.
[http://dx.doi.org/10.1093/brain/114.5.2283] [PMID: 1933245]
[37]
Parkinson’s Disease Foundation; Statistics on Parkinson’s 2013.Available from. http://www.pdf.org/en/parkinson_statistics
[38]
Olanow CW. The scientific basis for the current treatment of Parkinson’s disease. Annu Rev Med 2004; 55: 41-60.
[http://dx.doi.org/10.1146/annurev.med.55.091902.104422] [PMID: 14746509]
[39]
Jellinger K. The pathology of Parkinsonism Movement Disorders 2. UK: Butterworth- Heinemann 1987; pp. 124-65..
[40]
Reich SG, Savitt JM. Parkinson’s disease. Med Clin North Am 2019; 103(2): 337-50.
[http://dx.doi.org/10.1016/j.mcna.2018.10.014] [PMID: 30704685]
[41]
Elkouzi A, Vedam-Mai V, Eisinger RS, Okun MS. Emerging therapies in Parkinson disease - repurposed drugs and new approaches. Nat Rev Neurol 2019; 15(4): 204-23.
[http://dx.doi.org/10.1038/s41582-019-0155-7] [PMID: 30867588]
[42]
Olanow CW, Kieburtz K, Odin P, et al. LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled,double-blind, double-dummy study. Lancet Neurol 2014; 13(2): 141-9.
[http://dx.doi.org/10.1016/S1474-4422(13)70293-X] [PMID: 24361112]
[43]
Marsden CD. Parkinson’s disease. Lancet 1990; 335(8695): 948-52.
[http://dx.doi.org/10.1016/0140-6736(90)91006-V] [PMID: 1691427]
[44]
Olanow CW, Fahn S, Muenter M, et al. A multicenter double-blind placebo- controlled trial of pergolide as an adjunct to Sine met in Parkinson’s disease. Mov Disord 1994; 9: 40-7.
[http://dx.doi.org/10.1002/mds.870090107] [PMID: 8139604]
[45]
Shoulson I. DATATOP: a decade of neuroprotective inquiry. Deprenyl and tocopherol antioxidative therapy of Parkinsonism. Ann Neurol 1998; 44(3)(Suppl. 1): S160-6.
[http://dx.doi.org/10.1002/ana.410440724] [PMID: 9749589]
[46]
Nutt JG. Catechol-O-methyltransferase inhibitors for treatment of Parkinson’s disease. Lancet 1998; 351(9111): 1221-2.
[http://dx.doi.org/10.1016/S0140-6736(05)79311-9] [PMID: 9643737]
[47]
Fahn S, Oakes D, Shoulson I, et al. Levodopa andtheprogressionof Parkinson’s disease. N Engl J Med 2004; 351: 2498-508.
[PMID: 15590952]
[48]
Hamani C, Neimat JS, Lozano AM. Deep brain stimulation and chemical neuromodulation: current use and perspectives for the future. Acta Neurochir Suppl (Wien) 2007; 97(Pt 2): 127-33.
[http://dx.doi.org/10.1007/978-3-211-33081-4_15] [PMID: 17691298]
[49]
Buhmann C, Huckhagel T, Engel K, et al. Adverse events in deep brain stimulation: A retrospective long-term analysis of neurological, psychiatric and other occurrences. PLoS One 2017; 12(7) e0178984
[http://dx.doi.org/10.1371/journal.pone.0178984] [PMID: 28678830]
[50]
Sian J, Gerlach M, Youdim MB, Riederer P. Parkinson’s disease: a major hypokinetic basal ganglia disorder. J Neural Transm (Vienna) 1999; 106(5-6): 443-76.
[http://dx.doi.org/10.1007/s007020050171] [PMID: 10443550]
[51]
Blomstedt P, Hariz MI. Are complications less common in deep brain stimulation than in ablative procedures for movement disorders? Stereotact Funct Neurosurg 2006; 84(2-3): 72-81.
[http://dx.doi.org/10.1159/000094035] [PMID: 16790989]
[52]
Hitti FL, Yang AI, Gonzalez-Alegre P, Baltuch GH. Human gene therapy approaches for the treatment of Parkinson’s disease: An overview of current and completed clinical trials. Parkinsonism Relat Disord 2019; 66: 16-24.
[http://dx.doi.org/10.1016/j.parkreldis.2019.07.018] [PMID: 31324556]
[53]
Mali S. Delivery systems for gene therapy. Indian J Hum Genet 2013; 19(1): 3-8.
[http://dx.doi.org/10.4103/0971-6866.112870]
[54]
Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-associated virus-based gene therapy for CNS diseases. Hum Gene Ther 2016; 27(7): 478-96.
[http://dx.doi.org/10.1089/hum.2016.087] [PMID: 27267688]
[55]
Marquez Loza LI, Yuen EC, McCray PB Jr. Lentiviral vectors for the treatment and prevention of cystic fibrosis lung disease. Genes (Basel) 2019; 10(3) E218
[http://dx.doi.org/10.3390/genes10030218] [PMID: 30875857]
[56]
Wells DJ. Gene therapy progress and prospects: electroporation and other physical methods. Gene Ther 2004; 11(18): 1363-9.
[http://dx.doi.org/10.1038/sj.gt.3302337] [PMID: 15295618]
[57]
Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Commun Signal 2013; 11(1): 34.
[http://dx.doi.org/10.1186/1478-811X-11-34] [PMID: 23683503]
[58]
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]
[59]
Caudle WM, Colebrooke RE, Emson PC, Miller GW. Altered vesicular dopamine storage in Parkinson’s disease: a premature demise. Trends Neurosci 2008; 31(6): 303-8.
[http://dx.doi.org/10.1016/j.tins.2008.02.010] [PMID: 18471904]
[60]
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]
[61]
Zheng B, Liao Z, Locascio JJ, et al. PGC-1α, a potential therapeutic target for early intervention in Parkinson’s disease. Sci Transl Med 2010; 2(52): 52-73.
[http://dx.doi.org/10.1126/scitranslmed.3001059] [PMID: 20926834]
[62]
Kaplitt MG, Leone P, Samulski RJ, et al. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet 1994; 8(2): 148-54.
[http://dx.doi.org/10.1038/ng1094-148] [PMID: 7842013]
[63]
Björklund T, Kirik D. Scientific rationale for the development of gene therapy strategies for Parkinson’s disease. Biochim Biophys Acta 2009; 1792(7): 703-13.
[http://dx.doi.org/10.1016/j.bbadis.2009.02.009] [PMID: 19254760]
[64]
Carlsson T, Björklund T, Kirik D. Restoration of the striatal dopamine synthesis for Parkinson’s disease: viral vector-mediated enzyme replacement strategy. Curr Gene Ther 2007; 7(2): 109-20.
[http://dx.doi.org/10.2174/156652307780363125] [PMID: 17430130]
[65]
Shen Y, Muramatsu SI, Ikeguchi K, et al. Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson’s disease. Hum Gene Ther 2000; 11(11): 1509-19.
[http://dx.doi.org/10.1089/10430340050083243] [PMID: 10945765]
[66]
Lanciego JL, Luquin N, Obeso JA. Functional neuroanatomy of the basal ganglia. Cold Spring Harb Perspect Med 2012; 2(12): a009621-1.
[http://dx.doi.org/10.1101/cshperspect.a009621] [PMID: 23071379]
[67]
Rodnitzky RL. Upcoming treatments in Parkinson’s disease, including gene therapy. Parkinsonism Relat Disord 2012; 18(Suppl. 1): 37-40.
[http://dx.doi.org/10.1016/s1353-8020(11)70014-1] [PMID: 22166449]
[68]
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(1): 84-91.
[http://dx.doi.org/10.1016/S1474-4422(12)70295-8] [PMID: 23237903]
[69]
Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001; 344(10): 710-9.
[http://dx.doi.org/10.1056/NEJM200103083441002] [PMID: 11236774]
[70]
Ma Y, Feigin A, Dhawan V, et al. Dyskinesia after fetal cell transplantation for Parkinsonism: a PET study. Ann Neurol 2002; 52(5): 628-34.
[http://dx.doi.org/10.1002/ana.10359] [PMID: 12402261]
[71]
Hagell P, Piccini P, Björklund A, et al. Dyskinesias following neural transplantation in Parkinson’s disease. Nat Neurosci 2002; 5(7): 627-8.
[http://dx.doi.org/10.1038/nn863] [PMID: 12042822]
[72]
Carlsson T, Winkler C, Lundblad M, Cenci MA, Björklund A, Kirik D. Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia. Neurobiol Dis 2006; 21(3): 657-68.
[http://dx.doi.org/10.1016/j.nbd.2005.09.008] [PMID: 16256359]
[73]
Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 2000; 18(6): 675-9.
[http://dx.doi.org/10.1038/76536] [PMID: 10835609]
[74]
Kim JH, Auerbach JM, Rodríguez-Gómez JA, et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 2002; 418(6893): 50-6.
[http://dx.doi.org/10.1038/nature00900] [PMID: 12077607]
[75]
GForce-PD; A new global initiative around stem cell based therapies for Parkinson’s disease 2014.Available from. http://www.gforce-pd.com/
[76]
Addis RC, Hsu FC, Wright RL, Dichter MA, Coulter DA, Gearhart JD. Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector. PLoS One 2011; 6(12) e28719
[http://dx.doi.org/10.1371/journal.pone.0028719] [PMID: 22174877]
[77]
Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell 2010; 140(6): 918-34.
[http://dx.doi.org/10.1016/j.cell.2010.02.016] [PMID: 20303880]
[78]
Muffat J, Li Y, Yuan B, et al. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med 2016; 22(11): 1358-67.
[http://dx.doi.org/10.1038/nm.4189] [PMID: 27668937]
[79]
Ben Haim L, Carrillo-de Sauvage MA, Ceyzériat K, Escartin C. Elusive roles for reactive astrocytes in neurodegenerative diseases. Front Cell Neurosci 2015; 9: 278.
[http://dx.doi.org/10.3389/fncel.2015.00278] [PMID: 26283915]
[80]
Hong M, Mukhida K, Mendez I. GDNF therapy for Parkinson’s disease. Expert Rev Neurother 2008; 8(7): 1125-39.
[http://dx.doi.org/10.1586/14737175.8.7.1125] [PMID: 18590482]
[81]
Bespalov MM, Saarma M. GDNF family receptor complexes are emerging drug targets. Trends Pharmacol Sci 2007; 28(2): 68-74.
[http://dx.doi.org/10.1016/j.tips.2006.12.005] [PMID: 17218019]
[82]
Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993; 260(5111): 1130-2.
[http://dx.doi.org/10.1126/science.8493557] [PMID: 8493557]
[83]
Sauer H, Rosenblad C, Björklund A. Glial cell line-derived neurotrophic factor but not transforming growth factor β 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion. Proc Natl Acad Sci USA 1995; 92(19): 8935-9.
[http://dx.doi.org/10.1073/pnas.92.19.8935] [PMID: 7568047]
[84]
Kramer ER, Liss B. GDNF-Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease. FEBS Lett 2015; 589(24 Pt A): 3760-72.
[http://dx.doi.org/10.1016/j.febslet.2015.11.006] [PMID: 26555190]
[85]
Sauer H, Oertel WH. Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocyto chemical study in the rat. Neuroscience 1994; 59(2): 401-15.
[http://dx.doi.org/10.1016/0306-4522(94)90605-X] [PMID: 7516500]
[86]
Bowenkamp KE, Hoffman AF, Gerhardt GA, et al. Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons. J Comp Neurol 1995; 355(4): 479-89.
[http://dx.doi.org/10.1002/cne.903550402] [PMID: 7636027]
[87]
Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380(6571): 252-5.
[http://dx.doi.org/10.1038/380252a0] [PMID: 8637574]
[88]
Zhang Z, Miyoshi Y, Lapchak PA, et al. Dose response to intraventricular glial cell line- derived neurotrophic factor administration inparkinsonianmonkeys. J Pharmacol Exp Ther 1997; 282: 1396-401.
[PMID: 9316852]
[89]
Kozlowski DA, Connor B, Tillerson JL, Schallert T, Bohn MC. Delivery of a GDNF gene into the substantia nigra after a progressive 6-OHDA lesion maintains functional nigrostriatal connections. Exp Neurol 2000; 166(1): 1-15.
[http://dx.doi.org/10.1006/exnr.2000.7463] [PMID: 11031079]
[90]
Choi-Lundberg DL, Lin Q, Schallert T, et al. Behavioral and cellular protection of rat dopaminergic neurons by an adenoviral vector encoding glial cell line-derived neurotrophic factor. Exp Neurol 1998; 154(2): 261-75.
[http://dx.doi.org/10.1006/exnr.1998.6887] [PMID: 9878166]
[91]
Connor B, Kozlowski DA, Schallert T, Tillerson JL, Davidson BL, Bohn MC. Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat. Gene Ther 1999; 6(12): 1936-51.
[http://dx.doi.org/10.1038/sj.gt.3301033] [PMID: 10637445]
[92]
Mandel RJ, Spratt SK, Snyder RO, Leff SE. Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson’s disease in rats. Proc Natl Acad Sci USA 1997; 94(25): 14083-8.
[http://dx.doi.org/10.1073/pnas.94.25.14083] [PMID: 9391156]
[93]
Wang L, Muramatsu S, Lu Y, et al. Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson’s disease. Gene Ther 2002; 9(6): 381-9.
[http://dx.doi.org/10.1038/sj.gt.3301682] [PMID: 11960314]
[94]
Brizard M, Carcenac C, Bemelmans AP, Feuerstein C, Mallet J, Savasta M. Functional reinnervation from remaining DA terminals induced by GDNF lentivirus in a rat model of early Parkinson’s disease. Neurobiol Dis 2006; 21(1): 90-101.
[http://dx.doi.org/10.1016/j.nbd.2005.06.015] [PMID: 16084732]
[95]
Eslamboli A, Georgievska B, Ridley RM, et al. Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson’s disease. J Neurosci 2005; 25(4): 769-77.
[http://dx.doi.org/10.1523/JNEUROSCI.4421-04.2005] [PMID: 15673656]
[96]
Palfi S, Leventhal L, Chu Y, et al. Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. J Neurosci 2002; 22(12): 4942-54.
[http://dx.doi.org/10.1523/JNEUROSCI.22-12-04942.2002] [PMID: 12077191]
[97]
Georgievska B, Kirik D, Björklund A. Aberrant sprouting and downregulation of tyrosine hydroxylase in lesioned nigrostriatal dopamine neurons induced by long-lasting overexpression of glial cell line derived neurotrophic factor in the striatum by lentiviral gene transfer. Exp Neurol 2002; 177(2): 461-74.
[http://dx.doi.org/10.1006/exnr.2002.8006] [PMID: 12429192]
[98]
Apostolides C, Sanford E, Hong M, Mendez I. Glial cell line-derived neurotrophic factor improves intrastriatal graft survival of stored dopaminergic cells. Neuroscience 1998; 83(2): 363-72.
[http://dx.doi.org/10.1016/S0306-4522(97)00369-2] [PMID: 9460746]
[99]
Mehta V, Hong M, Spears J, Mendez I. Enhancement of graft survival and sensorimotor behavioral recovery in rats undergoing transplantation with dopaminergic cells exposed to glial cell line-derived neurotrophic factor. J Neurosurg 1998; 88(6): 1088-95.
[http://dx.doi.org/10.3171/jns.1998.88.6.1088] [PMID: 9609305]
[100]
Hebb AO, Hebb K, Ramachandran AC, Mendez I. Glial cell line-derived neurotrophic factor-supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage. J Neurosurg 2003; 98(5): 1078-83.
[http://dx.doi.org/10.3171/jns.2003.98.5.1078] [PMID: 12744369]
[101]
Mendez I, Dagher A, Hong M, et al. Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line--derived neurotrophic factor in patients with Parkinson’s disease. Report of two cases and technical considerations. J Neurosurg 2000; 92(5): 863-9.
[http://dx.doi.org/10.3171/jns.2000.92.5.0863] [PMID: 10794303]
[102]
Tatard VM, Sindji L, Branton JG, et al. Pharmacologically active micro carriers releasing glial cell line - derived neurotrophic factor: Survival and differentiation of embryonic dopaminergic neurons after grafting in hemi parkinsonian rats. Biomaterials 2007; 28(11): 1978-88.
[http://dx.doi.org/10.1016/j.biomaterials.2006.12.021] [PMID: 17240442]
[103]
Grandoso L, Ponce S, Manuel I, et al. Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats. Int J Pharm 2007; 343(1-2): 69-78.
[http://dx.doi.org/10.1016/j.ijpharm.2007.05.027] [PMID: 17583454]
[104]
Aron L, Klein P, Pham TT, Kramer ER, Wurst W, Klein R. Pro-survival role for Parkinson’s associated gene DJ-1 revealed in trophically impaired dopaminergic neurons. PLoS Biol 2010; 8(4) e1000349
[http://dx.doi.org/10.1371/journal.pbio.1000349] [PMID: 20386724]
[105]
Decressac M, Kadkhodaei B, Mattsson B, Laguna A, Perlmann T, Björklund A. α-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Sci Transl Med 2012; 4(163) 163ra156
[http://dx.doi.org/10.1126/scitranslmed.3004676] [PMID: 23220632]
[106]
Kazlauskaite A, Martínez-Torres RJ, Wilkie S, et al. Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation. EMBO Rep 2015; 16(8): 939-54.
[http://dx.doi.org/10.15252/embr.201540352] [PMID: 26116755]
[107]
Gasser T, Hardy J, Mizuno Y. Milestones in PD genetics. Mov Disord 2011; 26(6): 1042-8.
[http://dx.doi.org/10.1002/mds.23637] [PMID: 21626549]
[108]
Meka DP, Müller-Rischart AK, Nidadavolu P, et al. Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. J Clin Invest 2015; 125(5): 1873-85.
[http://dx.doi.org/10.1172/JCI79300] [PMID: 25822020]
[109]
ALS CNTF Treatment Study Group. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology 1996; 46(5): 1244-9.
[http://dx.doi.org/10.1212/WNL.46.5.1244] [PMID: 8628460]
[110]
Patel NK, Gill SS. GDNF delivery for Parkinson’s disease. Acta Neurochir Suppl (Wien) 2007; 97(Pt 2): 135-54.
[PMID: 17691299]
[111]
Thorne RG, Frey WH II. Delivery of neurotrophic factors to the central nervous system: pharmacokinetic considerations. Clin Pharmacokinet 2001; 40(12): 907-46.
[http://dx.doi.org/10.2165/00003088-200140120-00003] [PMID: 11735609]
[112]
Aebischer P, Ridet J. Recombinant proteins for neurodegenerative diseases: the delivery issue. Trends Neurosci 2001; 24(9): 533-40.
[http://dx.doi.org/10.1016/S0166-2236(00)01899-3] [PMID: 11506887]
[113]
Eriksdotter Jönhagen M, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 1998; 9(5): 246-57.
[http://dx.doi.org/10.1159/000017069] [PMID: 9701676]
[114]
Kordower JH, Palfi S, Chen EY, et al. Clinic pathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson’s disease. Ann Neurol 1999; 46(3): 419-24.
[http://dx.doi.org/10.1002/1531-8249(199909)46:3<419:AID-ANA21>3.0.CO;2-Q] [PMID: 10482276]
[115]
Nutt JG, Burchiel KJ, Comella CL, et al. ICV GDNF Study Group. Implanted intracerebroventricular. Glial cell line-derived neurotrophic factor. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 2003; 60(1): 69-73.
[http://dx.doi.org/10.1212/WNL.60.1.69] [PMID: 12525720]
[116]
Grondin R, Zhang Z, Yi A, et al. Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 2002; 125(Pt 10): 2191-201.
[http://dx.doi.org/10.1093/brain/awf234] [PMID: 12244077]
[117]
Patel NK, Bunnage M, Plaha P, Svendsen CN, Heywood P, Gill SS. Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann Neurol 2005; 57(2): 298-302.
[http://dx.doi.org/10.1002/ana.20374] [PMID: 15668979]
[118]
Hotton GR, Patel NK, Gill SS, Heywood P, Svendson SN. The long term effect of glial derived neurotrophic factor infusions and 18F-dopa uptake in Parkinson’s disease. Neurology 2020.
[119]
Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg 2005; 102(2): 216-22.
[http://dx.doi.org/10.3171/jns.2005.102.2.0216] [PMID: 15739547]
[120]
Lang AE, Gill SS, Patel NK, Lozano AM, Nutt JG, Penn R. Randomized controlled trial of intraputamenal GDNF infusion inParkinson disease. Ann Neurol 2006; 59: 459-66.
[http://dx.doi.org/10.1002/ana.20737] [PMID: 16429411]
[121]
Flotte TR. Top five gene therapy stories of 2019. Hum Gene Ther 2019; 30(1): 1-2.
[http://dx.doi.org/10.1089/hum.2018.29080.trf] [PMID: 30628861]
[122]
Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 2016; 375(8): 730-9.
[http://dx.doi.org/10.1056/NEJMoa1600159] [PMID: 27557301]
[123]
Yue P, Miao W, Gao L, Zhao X, Teng J. Ultrasound-triggered effects of the microbubbles coupled to GDNF plasmid-loaded PEGylated liposomes in a rat model of Parkinson’s disease. Front Neurosci 2018; 12: 222.
[http://dx.doi.org/10.3389/fnins.2018.00222] [PMID: 29686604]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 3
Year: 2020
Published on: 17 August, 2020
Page: [207 - 222]
Pages: 16
DOI: 10.2174/1566523220999200817164051
Price: $65

Article Metrics

PDF: 40
HTML: 3