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<front>
<journal-meta>
<journal-id journal-id-type="doi">10.1002/(ISSN)1521-1878</journal-id>
<journal-id journal-id-type="publisher-id">BIES</journal-id>
<journal-title-group>
<journal-title xml:lang="en">BioEssays</journal-title>
<abbrev-journal-title abbrev-type="publisher" xml:lang="en">BioEssays</abbrev-journal-title>
</journal-title-group>
<issn publication-format="ppub">0265-9247</issn>
<issn publication-format="epub">1521-1878</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1002/bies.202400118</article-id>
<article-id pub-id-type="publisher-id">BIES202400118</article-id>
<article-categories>
<subj-group subj-group-type="overline" xml:lang="en">
<subject>REVIEW ESSAY</subject>
</subj-group>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>REVIEW ESSAY</subject>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>Prospects &amp; Overviews</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title xml:lang="en">The history and status of dopamine cell therapies for Parkinson's disease</article-title>
<alt-title alt-title-type="left-running-head">BARKER <sc>et al.</sc></alt-title>
</title-group>
<contrib-group>
<contrib id="bies202400118-cr-0001" contrib-type="author" corresp="yes">
<name>
<surname>Barker</surname>
<given-names>Roger A.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8843-7730</contrib-id>
<email>rab46@cam.ac.uk</email>
<xref ref-type="corresp" rid="correspondenceTo">*</xref>
<xref ref-type="aff" rid="bies202400118-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="bies202400118-cr-0002" contrib-type="author">
<name>
<surname>Björklund</surname>
<given-names>Anders</given-names>
</name>
<xref ref-type="aff" rid="bies202400118-aff-0002">
<sup>2</sup>
</xref>
</contrib>
<contrib id="bies202400118-cr-0003" contrib-type="author">
<name>
<surname>Parmar</surname>
<given-names>Malin</given-names>
</name>
<xref ref-type="aff" rid="bies202400118-aff-0002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="bies202400118-aff-0003">
<sup>3</sup>
</xref>
</contrib>
</contrib-group>
<aff id="bies202400118-aff-0001">
<label>
<sup>1</sup>
</label>

<named-content content-type="organisation-division">Department of Clinical Neurosciences and Cambridge Stem Cell Institute</named-content>

<named-content content-type="organisation-division">John van Geest Centre for Brain Repair</named-content>

<institution>University of Cambridge</institution>

<city>Cambridge</city>
 <country country="GB">UK</country>

</aff>
<aff id="bies202400118-aff-0002">
<label>
<sup>2</sup>
</label>

<named-content content-type="organisation-division">Department of Experimental Medical Science</named-content>

<named-content content-type="organisation-division">Wallenberg Neuroscience Center</named-content>

<institution>Lund University</institution>

<city>Lund</city>
 <country country="SE">Sweden</country>

</aff>
<aff id="bies202400118-aff-0003">
<label>
<sup>3</sup>
</label>

<named-content content-type="organisation-division">Department of Clinical Sciences Lund</named-content>

<named-content content-type="organisation-division">Lund Stem Cell Center and Division of Neurology</named-content>

<institution>Lund University</institution>

<city>Lund</city>
 <country country="SE">Sweden</country>

</aff>
<author-notes>
<corresp id="correspondenceTo"><label>*</label><bold>Correspondence</bold><break/>Roger A. Barker, Department of Clinical Neurosciences and Cambridge Stem Cell Institute, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.<break/> Email: <email>rab46@cam.ac.uk</email><break/></corresp>
</author-notes>
<pub-date date-type="pub" publication-format="electronic"><day>26</day>
<month>07</month>
<year>2024</year>
</pub-date><elocation-id>2400118</elocation-id>
<history>

<date date-type="rev-recd">
<day>26</day>
<month>06</month>
<year>2024</year>
</date>

<date date-type="received">
<day>23</day>
<month>05</month>
<year>2024</year>
</date>

<date date-type="accepted">
<day>01</day>
<month>07</month>
<year>2024</year>
</date>

</history>
<permissions>
<copyright-statement content-type="issue-copyright">© 2024 Wiley Periodicals LLC.</copyright-statement>
<copyright-statement content-type="article-copyright">© 2024 The Author(s). <italic>BioEssays</italic> published by Wiley Periodicals LLC.</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>© 2024 The Author(s). BioEssays published by Wiley Periodicals LLC.</copyright-holder>
<license>
<ali:license_ref>http://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open access article under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution</ext-link> License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract xml:lang="en" abstract-type="main">
<title>Abstract</title>
<p xml:lang="en">Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell‐derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP.</p>
</abstract>
<kwd-group kwd-group-type="author-generated" xml:lang="en">
<kwd id="bies202400118-kwd-0001">clinical trials</kwd>
<kwd id="bies202400118-kwd-0002">dopamine cell transplants</kwd>
<kwd id="bies202400118-kwd-0003">G Force PD</kwd>
<kwd id="bies202400118-kwd-0004">human fetal ventral mesencephalic tissue</kwd>
<kwd id="bies202400118-kwd-0005">human pluripotent stem cell‐derived dopamine cells</kwd>
<kwd id="bies202400118-kwd-0006">Parkinson's disease</kwd>
</kwd-group>
<funding-group>
<award-group id="funding-0001">
<funding-source>

<institution-wrap>
<institution>EU FP7</institution>
</institution-wrap>

</funding-source>
<award-id>242003</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0002">
<funding-source>

<institution-wrap>
<institution>Cure Parkinson's</institution>
</institution-wrap>

</funding-source>
<award-id>RG81537</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0003">
<funding-source>

<institution-wrap>
<institution>NIHR Cambridge Biomedical Research Centre</institution>
<institution-id>http://dx.doi.org/10.13039/501100018956</institution-id>
</institution-wrap>

</funding-source>
<award-id>NIHR203312</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0004">
<funding-source>

<institution-wrap>
<institution>New York Stem Cell Foundation</institution>
<institution-id>http://dx.doi.org/10.13039/100003194</institution-id>
</institution-wrap>

</funding-source>
<award-id>#NYSCF‐R‐I37</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0005">
<funding-source>

<institution-wrap>
<institution>Swedish Research Council</institution>
<institution-id>http://dx.doi.org/10.13039/501100004359</institution-id>
</institution-wrap>

</funding-source>
<award-id>2016‐00873 2021‐00661</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0006">
<funding-source>

<institution-wrap>
<institution>Swedish Brain Foundation</institution>
<institution-id>http://dx.doi.org/10.13039/501100003792</institution-id>
</institution-wrap>

</funding-source>
<award-id>FO2019‐0301</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0007">
<funding-source>

<institution-wrap>
<institution>European Research Council</institution>
<institution-id>http://dx.doi.org/10.13039/501100000781</institution-id>
</institution-wrap>

</funding-source>
<award-id>771427</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0008">
<funding-source>

<institution-wrap>
<institution>Novo Nordisk A/S, the Swedish Research Council</institution>
</institution-wrap>

</funding-source>
<award-id>2016‐00873 2021‐00661</award-id>
</award-group>
</funding-group>
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<fig-count count="1"/>
<table-count count="1"/>
<page-count count="10"/>
<word-count count="9450"/>
</counts>
</article-meta>
</front>
</article>