Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: Translation into a phase I controlled, randomized clinical study

Journal of Translational Medicine

Volumn 12, Issue 1, 2014, Pages

  Giordano, Rosaria ^a   Canesi, Margherita ^b   Isalberti, Maurizio ^a   Isaias, Ioannis U ^b,c   Montemurro, Tiziana ^a   Viganò, Mariele ^a   Montelatici, Elisa ^a   Boldrin, Valentina ^a   Benti, Riccardo ^a   Cortelezzi, Agostino ^d   Fracchiolla, Nicola ^d   Lazzari, Lorenza ^a   Pezzoli, Gianni ^b  

^a FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

^b Parkinson Center   (Italy)

^c UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^d UNIVERSITY OF MILAN   (Italy)

Author keywords

Advanced therapy medicinal products; Cellular therapy; Mesenchymal stem and stromal cells; Parkinson's disease; Progressive supranuclear palsy

Indexed keywords

ADULT; CELL LINE, TUMOR; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; NERVE GROWTH FACTORS; SUPRANUCLEAR PALSY, PROGRESSIVE; TRANSLATIONAL MEDICAL RESEARCH; TRANSPLANTATION, AUTOLOGOUS;

EID: 84892462886     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/1479-5876-12-14     Document Type: Article

References (67)

1. Nath U, Ben-Shlomo Y, Thomson RG, Morris HR, Wood NW, Lees AJ, Burn DJ. The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain 2001, 124:1438-1449.
2. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology 1997, 49:1284-1288.
3. Ludolph AC, et al. Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers and treatment options. Eur J Neurol 2009, 16:297-309.
4. Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996, 47:1-9.
5. Litvan I, Campbell G, Mangone CA, Verny M, McKee A, Chaudhuri KR, Jellinger K, Pearce RK, D'Olhaberriague L. Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? A clinicopathological study. Brain 1997, 120:65-74.
6. Karakaya T, Fußer F, Prvulovic D, Hampel H. Treatment options for tauopathies. Curr Treat Options Neurol 2012, 14:126-36.
7. Zampieri C, Di Fabio RP. Progressive supranuclear palsy: disease profile and rehabilitation strategies. Phys Ther 2006, 86:870-880.
8. Nath U, Ben-Shlomo Y, Thomson RG, Lees AJ, Burn DJ. Clinical features and natural history of pregressive supranuclear palsy. A clinical cohort study. Neurology 2003, 60:910-916.
9. Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK, Movement Disorders Society Scientific Issues Committee Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 2003, 18:467-486. Movement Disorders Society Scientific Issues Committee.
10. Golbe LI. Neurodegeneration in the age of molecular biology. BMJ 2002, 324:1467-1468.
11. Ferrer I, López-González I, Carmona M, Arregui L, Dalfó E, Torrejón-Escribano B, Diehl R, Kovacs GG. Glial and neuronal tau pathology in tauopathies: characterization of disease-specific phenotypes and tau pathology progression. J Neuropathol Exp Neurol 2014, 73:81-97.
12. Ghawche F, Durif F. Dopaminergic treatment and parkinsonian syndromes. Rev Neurol 2003, 159:3S83-3S86.
13. Hilker R, Benecke R, Deuschl G, Fogel W, Kupsch A, Schrader C, Sixel-Döring F, Timmermann L, Volkmann J, Lange M, German Deep Brain Stimulation Association Deep brain stimulation for Parkinson's disease. Consensus recommendations of the German Deep Brain Stimulation Association. Nervenarzt 2009, 80:646-655. German Deep Brain Stimulation Association.
14. Silberstein P, Bittar RG, Boyle R, Cook R, Coyne T, O'Sullivan D, Pell M, Peppard R, Rodrigues J, Silburn P, Stell R, Watson P, Australian DBS Referral Guidelines Working Group Deep brain stimulation for Parkinson's disease: Australian referral guidelines. J Clin Neurosci 2009, 16:1001-1008. Australian DBS Referral Guidelines Working Group.
15. von Bahr L, Sundberg B, Lönnies L, Sander B, Karbach H, Hägglund H, Ljungman P, Gustafsson B, Karlsson H, Le Blanc K, Ringdén O. Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 2012, 18:557-564.
16. Wang S, Cheng H, Dai G, Wang X, Hua R, Liu X, Wang P, Chen G, Yue W, An Y. Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury. Brain Res 2013, Epub ahead of print.
17. Jiang PC, Xiong WP, Wang G, Ma C, Yao WQ, Kendell SF, Mehling BM, Yuan XH, Wu DC. A clinical trial report of autologous bone marrow-derived mesenchymal stem cell transplantation in patients with spinal cord injury. Exp Ther Med. 2013, 6:140-146.
18. Tzouvelekis A, Paspaliaris V, Koliakos G, Ntolios P, Bouros E, Oikonomou A, Zissimopoulos A, Boussios N, Dardzinski B, Gritzalis D, Antoniadis A, Froudarakis M, Kolios G, Bouros D. A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis. J Transl Med 2013, 11:171.
19. Yamada Y, Nakamura S, Ito K, Umemura E, Hara K, Nagasaka T, Abe A, Baba S, Furuichi Y, Izumi Y, Klein OD, Wakabayashi T. Injectable bone tissue engineering using expanded mesenchymal stem cells. Stem Cells 2013, 31:572-80.
20. Blum R, Konnerth A. Neurotrophin-mediated rapid signaling in the central nervous system: mechanisms and functions. Physiology 2005, 20:70-8.
21. Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P. BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature 2001, 411:86-9.
22. Airaksinen MS, Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 2002, 3:383-94.
23. Ugarte SD, Lin E, Klann E, Zigmond MJ, Perez RG. Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: modulation by inhibitors of PI3 kinase and MEK. J Neurosci Res 2003, 73:105-12.
24. Poteryaev D, Titievsky A, Sun YF, Thomas-Crusells J, Lindahl M, Billaud M, Arumäe U, Saarma M. GDNF triggers a novel ret-independent Src kinase family-coupled signaling via a GPI-linked GDNF receptor alpha1. FEBS Lett 1999, 463:63-6.
25. Besset V, Scott RP, Ibáñez CF. Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase. J Biol Chem 2000, 275:39159-66.
26. Coulpier M, Anders J, Ibáñez CF. Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J Biol Chem 2002, 277:1991-9.
27. Lin MN, Shang DS, Sun W, Li B, Xu X, Fang WG, Zhao WD, Cao L, Chen YH. Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers. Brain Res 2013, 1513:1-8.
28. Brazzini A, Cantella R, De la Cruz A, Yupanqui J, León C, Jorquiera T, Brazzini M, Ortega M, Saenz LN. Intraarterial autologous implantation of adult stem cells for patients with Parkinson disease. J Vasc Interv Radiol 2010, 21:443-451.
29. Bruno S, Camussi G. Role of mesenchymal stem cell-derived microvesicles in tissue repair. Pediatr Nephrol 2013, 28:2249-54.
30. Quattrone A, Nicoletti G, Messina D, Fera F, Condino F, Pugliese P, Lanza P, Barone P, Morgante L, Zappia M, Aguglia U, Gallo O. MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology 2008, 246:214-21.
31. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N, Movement Disorder Society UPDRS Revision Task Force Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008, 23:2129-70. Movement Disorder Society UPDRS Revision Task Force.
32. Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 2004, 19:1020-8.
33. Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain 2007, 130:1152-65.
34. Streiner DL, Norman GR. Health measurement scales: a practical guide to their development and use 2003, Oxford: Oxford University Press, 9780199231881, doi:10.1093/acprof:oso/9780199231881.001.0001.
35. Crenna P, Carpinella I, Lopiano L, Marzegan A, Rabuffetti M, Rizzone M, Lanotte M, Ferrarin M. Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease. Brain 2008, 131:3410-20.
36. Folstein MF, Folstein SE, McHugh PR. " Mini-mental state" A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975, 12:189-98.
37. Jenkinson C, Fitzpatrick R. Cross-cultural evaluation of the short form 8-item Parkinson's disease Questionnaire (PDQ-8): results from America, Canada, Japan, Italy and Spain. Parkinsonism Relat Disord 2007, 13:22-28.
38. National Cancer Institute Common Toxicity Criteria Manual (CTCAE v 4.0) available at http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_mapping_docs.
39. Goetz CG, Olanow CW, Koller WC, Penn RD, Cahill D, Morantz R, Stebbins G, Tanner CM, Klawans HL, Shannon KM. Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease. N Engl J Med 1989, 320:337-341.
40. Pezzoli G, Motti E, Zecchinelli A, Ferrante C, Silani V, Falini A, Pizzuti A, Mulazzi D, Baratta P, Vegeto A. Adrenal medulla autograft in 3 parkinsonian patients: results using two different approaches. Prog Brain Res 1990, 82:677-682.
41. Olanow CW, Koller W, Goetz CG, Stebbins TG, Cahill DW, Gauger LL, Morantz R, Penn RD, Tanner CM, Klawans HL, Shannon KM, Comella CL, Witt T. Autologous transplantation of adrenal medulla in Parkinson's disease: 18-month results. Arch Neurol 1990, 47:1286-1289.
42. Fazzini E, Dwork AJ, Blum C, Burke R, Cote L, Goodman RR, Jacobs TP, Naini AB, Pezzoli G, Pullman S, Solomon RA, Truong D, Weber CJ, Fahn S. Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One year follow-up. Arch Neurol 1991, 48:813-820.
43. Fazzini E. Transplantation in the treatment of paralysis agitans (Parkinson's disease). J Am Osteopath Assoc 1992, 92:1255-1260.
44. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. New Engl J Med 2001, 344:710-719.
45. Ma Y, Feigin A, Dhawan V, Fukuda M, Shi Q, Greene P, Breeze R, Fahn S, Freed C, Eidelberg D. Dyskinesia after fetal cell transplantation for parkinsonism: PET study. Ann Neurol 2002, 52:628-634.
46. Politis M, Wu K, Loane C, Quinn NP, Brooks DJ, Rehncrona S, Bjorklund A, Lindvall O, Piccini P. Serotonergic neurons mediate dyskinesia side effects in Parkinson's patients with neural transplants. Sci Transl Med 2010, 2:38-46.
47. Lindvall O, Kokaia Z. Prospects of stem cell therapy for replacing dopamine neurons in Parkinson's disease. Trends Pharmacol Sci 2009, 30:260-7.
48. Olanow CW, Kordower JH, Lang AE, Obeso JA. Dopaminergic transplantation for Parkinson's disease: current status and future prospects. Ann Neurol 2009, 66:591-6.
49. Arias-Carrion O, Yuan TF. Autologous neural stem cell transplantation: a new treatment option for Parkinson's disease?. Med Hypotheses 2009, 73:757-759.
50. Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci 1997, 94:4080-4085.
51. Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000, 290:1779-1782.
52. Cogle CR, Yachnis AT, Laywell ED, Zander DS, Wingard JR, Steindler DA, Scott EW. Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet 2004, 363:1432-7.
53. Cova L, Bossolasco P, Armentero MT, Diana V, Zennaro E, Mellone M, Calzarossa C, Cerri S, Deliliers GL, Polli E, Blandini F, Silani V. Neuroprotective effects of human mesenchymal stem cells on neural cultures exposed to 6-hydroxydopamine: implications for reparative therapy in Parkinson's disease. Apoptosis 2012, 17:289-304.
54. Cova L, Armentero MT, Zennaro E, Calzarossa C, Bossolasco P, Busca G, Lambertenghi Deliliers G, Polli E, Nappi G, Silani V, Blandini F. Multiple neurogenic and neurorescue effects of human mesenchymal stem cell after transplantation in an experimental model of Parkinson's disease. Brain Res 2010, 1311:12-27.
55. Blandini F, Cova L, Armentero MT, Zennaro E, Levandis G, Bossolasco P, Calzarossa C, Mellone M, Giuseppe B, Deliliers GL, Polli E, Nappi G, Silani V. Transplantation of undifferentiated human mesenchymal stem cells protects against 6-hydroxydopamine neurotoxicity in the rat. Cell Transplant 2010, 203-17.
56. Lee PH, Park HJ. Bone-marrow-derived mesenchymal stem cell therapy as a candidate disease-modifying strategy in Parkinson's disease. Multiple system atrophy. J Clin Neurol 2009, 5:1-10.
57. Giordano A, Galderisi U, Marino IR. From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 2007, 211:27-35.
58. Zhang Z, Wang X, Wang S. Isolation and characterization of mesenchymal stem cells derived from bone marrow of patients with Parkinson's disease. In Vitro Cell Dev Biol Anim 2008, 44(5-6):169-77.
59. Park HJ, Lee PH, Bang OY, Lee G, Ahn YH. Mesenchymal stem cells therapy exerts neuroprotection in a progressive animal model of Parkinson's disease. J Neurochem 2008, 107:141-151.
60. Kim YJ, Park HJ, Lee G, Bang OY, Ahn YH, Joe E, Kim HO, Lee PH. Neuroprotective effects of human mesenchymal stem cells on dopaminergic neurons through anti-inflammatory action. Glia 2009, 57:13-23.
61. Jin GZ, Cho SJ, Choi EG, Lee YS, Yu XF, Choi KS, Yee ST, Jeon JT, Kim MO, Kong IK. Rat mesenchymal stem cells increase tyrosine hydroxylase expressioni and dopamine content in ventral mesencephalic cells in vitro. Cell Biol Int 2008, 32(11):1433-8.
62. Sadan O, Bahat-Stromza M, Barhum Y, Levy YS, Pisnevsky A, Peretz H, Ilan AB, Bulvik S, Shemesh N, Krepel D, Cohen Y, Melamed E, Offen D. Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of Parkinson disease. Stem Cells Dev 2009, 18(8):1179-90.
63. Lee PH, Kim JW, Bang OY, Ahn YH, Joo IS, Huh K. Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clin Pharmacol Ther 2008, 83:723-730.
64. Lee PH, Lee JE, Kim HS, Song SK, Lee HS, Nam HS, Cheong JW, Jeong Y, Park HJ, Kim DJ, Nam CM, Lee JD, Kim HO, Sohn YH. A randomized trial of mesenchymal stem cells in multiple system atrophy. Ann Neurol 2012, 72:32-40.
65. Venkataramana NK, Kumar SK, Balaraju S, Radhakrishnan RC, Bansal A, Dixit A, Rao DK, Das M, Jan M, Gupta PK, Totey SM. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease. Transl Res 2010, 155:62-70.
66. Everaert BR, Bergwerf I, De Vocht N, Ponsaerts P, Van Der Linden A, Timmermans JP, Vrints CJ. Multimodal in vivo imaging reveals limited allograft survival, intrapulmonary cell trapping and minimal evidence for ischemia-directed bone marrow-derived stromal cell homing. BMC Biotechnol 2012, 12:93.
67. Camp DM, Loeffler DA, Farrah DM, Borneman JN, LeWitt PA. Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease. J Neuroinflammation 2009, 6:17.