4.6 Article

Graft-Induced Dyskinesias in Parkinson's Disease: High Striatal Serotonin/Dopamine Transporter Ratio

Journal

MOVEMENT DISORDERS
Volume 26, Issue 11, Pages 1997-2003

Publisher

WILEY
DOI: 10.1002/mds.23743

Keywords

Parkinson; transplantation; dyskinesias; serotonin transporter; dopamine transporter

Funding

  1. MRC [G1100810, MC_U120036861] Funding Source: UKRI
  2. Medical Research Council [G1100810, MC_U120036861] Funding Source: Medline
  3. Medical Research Council [G1100810, MC_U120036861] Funding Source: researchfish

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Graft-induced dyskinesias are a serious complication after neural transplantation in Parkinson's disease. One patient with Parkinson's disease, treated with fetal grafts 14 years ago and deep brain stimulation 6 years ago, showed marked improvement of motor symptoms but continued to suffer from OFF-medication graft-induced dyskinesias. The patient received a series of clinical and imaging assessments. Positron emission tomography and single-photon emission computed tomography 14 years posttransplantation revealed an elevated serotonin/dopamine transporter ratio in the grafted striatum compatible with serotonergic hyperinnervation. Inhibition of serotonin neuron activity by systemic administration of a 5-HT1A agonist suppressed graft-induced dyskinesias. Our data provide further evidence that serotonergic neurons mediate graft-induced dyskinesias in Parkinson's disease. Achieving a normal striatal serotonin/dopamine transporter ratio following transplantation of fetal tissue or stem cells should be necessary to avoid the development of graft-induced dyskinesias. (C) 2011 Movement Disorder Society

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