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Review: The future of cell therapies and brain repair: P arkinson's disease leads the way
Author(s) -
Petit G. H.,
Olsson T. T.,
Brundin P.
Publication year - 2014
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12110
Subject(s) - transplantation , dopamine , neuroscience , disease , medicine , clinical trial , bioinformatics , pathology , psychology , biology
During the past 40 years brain tissue grafting techniques have been used both to study fundamental neurobiological questions and to treat neurological diseases. Motor symptoms of P arkinson's disease are largely due to degeneration of midbrain dopamine neurones. Because the nigrostriatal pathology is relatively focused anatomically, P arkinson's disease is considered the ideal candidate for brain repair by neural grafting and dopamine neurone transplantation for it has led the way in the neural transplantation research field. In this mini‐review, we briefly highlight four important areas of development. First, we describe marked functional benefits up to 18 years after transplantation surgery in patients with P arkinson's disease. This is proof‐of‐principle that, using optimal techniques and patient selection, grafted dopamine neurones can work in humans and the duration of the benefit exceeds placebo effects associated with surgery. Second, we describe that eventually protein aggregates containing α‐synuclein, identical to L ewy bodies, develop inside foetal dopamine neurones transplanted to patients with P arkinson's disease. This gives clues about pathogenetic mechanisms operating in P arkinson's disease, and also raises the question whether neural graft function will eventually decline as the result of the disease process. Third, we describe new emerging sources of transplantable dopamine neurones derived from pluripotent stem cells or reprogrammed adult somatic cells. Fourth, we highlight an important E uropean U nion‐funded multicentre clinical trial involving transplantation of foetal dopamine neurones in P arkinson's disease. We describe the design of this ongoing trial and how it can impact on the overall future of cell therapy in P arkinson's disease.