Replacing Dopamine Neurons In Parkinson's Disease: How Did It Happen?

Overview

Journal J Parkinsons Dis

Publisher Sage Publications

Specialty Neurology

Date 2017 Mar 12

PMID 28282811

Citations 27

Authors

Anders Bjorklund

Olle Lindvall

Affiliations

Soon will be listed here.

Abstract

The efforts to develop a dopamine cell replacement therapy for Parkinson's disease have spanned over more than three decades. Based on almost 10 years of transplantation studies in animal models, the first patients receiving grafts of fetal-derived dopamine neuroblasts were operated in Lund in 1987. Over the following two decades, a total of 18 patients were transplanted and followed closely by our team with mixed but also very encouraging results. In this article we tell the story of how the preclinical and clinical transplantation program in Lund evolved. We recall the excitement when we obtained the first evidence for survival and function of transplanted neurons in the diseased human brain. We also remember the setbacks that we have experienced during these 30 years and discuss the very interesting developments that are now taking place in this exciting field.

Citing Articles

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Human cortical interneurons optimized for grafting specifically integrate, abort seizures, and display prolonged efficacy without over-inhibition.

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References

Brundin P, Nilsson O, Strecker R, Lindvall O, ASTEDT B, Bjorklund A . Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease. Exp Brain Res. 1986; 65(1):235-40. DOI: 10.1007/BF00243848. View

Sundberg M, Bogetofte H, Lawson T, Jansson J, Smith G, Astradsson A . Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells. 2013; 31(8):1548-62. PMC: 3775937. DOI: 10.1002/stem.1415. View

Bjorklund A, Stenevi U, Svendgaard N . Growth of transplanted monoaminergic neurones into the adult hippocampus along the perforant path. Nature. 1976; 262(5571):787-90. DOI: 10.1038/262787a0. View

Koepp M, Gunn R, Lawrence A, Cunningham V, Dagher A, Jones T . Evidence for striatal dopamine release during a video game. Nature. 1998; 393(6682):266-8. DOI: 10.1038/30498. View

Stenevi U, Bjorklund A, Svendgaard N . Transplantation of central and peripheral monoamine neurons to the adult rat brain: techniques and conditions for survival. Brain Res. 1976; 114(1):1-20. DOI: 10.1016/0006-8993(76)91003-9. View

Piccini P, Lindvall O, Bjorklund A, Brundin P, Hagell P, Ceravolo R . Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts. Ann Neurol. 2000; 48(5):689-95. View

Goetz C, Stebbins 3rd G, Klawans H, Koller W, Grossman R, Bakay R . United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up. Neurology. 1991; 41(11):1719-22. DOI: 10.1212/wnl.41.11.1719. View

Brundin P, Strecker R, Widner H, Clarke D, Nilsson O, ASTEDT B . Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp Brain Res. 1988; 70(1):192-208. DOI: 10.1007/BF00271860. View

Kirkeby A, Grealish S, Wolf D, Nelander J, Wood J, Lundblad M . Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Rep. 2012; 1(6):703-14. DOI: 10.1016/j.celrep.2012.04.009. View

10.

Olson L, Seiger A . Brain tissue transplanted to the anterior chamber of the eye. 1. Fluorescence histochemistry of immature catecholamine and 5-hydroxytryptamine neurons reinnervating the rat iris. Z Zellforsch Mikrosk Anat. 1972; 135(2):175-94. DOI: 10.1007/BF00315125. View

11.

Li W, Englund E, Widner H, Mattsson B, van Westen D, Latt J . Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain. Proc Natl Acad Sci U S A. 2016; 113(23):6544-9. PMC: 4988567. DOI: 10.1073/pnas.1605245113. View

12.

Piccini P, Brooks D, Bjorklund A, Gunn R, Grasby P, Rimoldi O . Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci. 1999; 2(12):1137-40. DOI: 10.1038/16060. View

13.

Kikuchi T, Morizane A, Doi D, Onoe H, Hayashi T, Kawasaki T . Survival of human induced pluripotent stem cell-derived midbrain dopaminergic neurons in the brain of a primate model of Parkinson's disease. J Parkinsons Dis. 2013; 1(4):395-412. DOI: 10.3233/JPD-2011-11070. View

14.

Lindvall O, Backlund E, Farde L, Sedvall G, Freedman R, Hoffer B . Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen. Ann Neurol. 1987; 22(4):457-68. DOI: 10.1002/ana.410220403. View

15.

Madrazo I, Leon V, Torres C, Aguilera M, Varela G, Alvarez F . Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson's disease. N Engl J Med. 1988; 318(1):51. DOI: 10.1056/NEJM198801073180115. View

16.

Freed W, Morihisa J, Spoor E, Hoffer B, Olson L, Seiger A . Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behaviour. Nature. 1981; 292(5821):351-2. DOI: 10.1038/292351a0. View

17.

Bjorklund A, Stenevi U, Dunnett S, Iversen S . Functional reactivation of the deafferented neostriatum by nigral transplants. Nature. 1981; 289(5797):497-9. DOI: 10.1038/289497a0. View

18.

Ungerstedt U, Arbuthnott G . Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res. 1970; 24(3):485-93. DOI: 10.1016/0006-8993(70)90187-3. View

19.

Brundin P, Isacson O, Bjorklund A . Monitoring of cell viability in suspensions of embryonic CNS tissue and its use as a criterion for intracerebral graft survival. Brain Res. 1985; 331(2):251-9. DOI: 10.1016/0006-8993(85)91550-1. View

20.

Perlow M, Freed W, Hoffer B, Seiger A, Olson L, Wyatt R . Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science. 1979; 204(4393):643-7. DOI: 10.1126/science.571147. View