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Carotid body autotransplantation in Parkinson disease: A clinical and PET study
  1. Adolfo Minguez-Castellanos
  1. University Hospital Virgen de las Nieves, Granada., Spain
    1. Francisco Escamilla-Sevilla
    1. University Hospital Virgen de las Nieves, Granada., Spain
      1. Gary R Hotton
      1. MRC Cyclotron Unit, Hammersmith Hospital, London, Spain
        1. Juan Jose Toledo-Aral
        1. University of Seville, Seville, Spain
          1. Angel Ortega-Moreno
          1. University Hospital Virgen de las Nieves, Granada., Spain
            1. Simon Mendez-Ferrer
            1. University of Seville, Seville, Spain
              1. Jose M Martin-Linares
              1. University Hospital Virgen de las Nieves, Granada., Spain
                1. Majed J Katati
                1. University Hospital Virgen de las Nieves, Granada., Spain
                  1. Pablo Mir
                  1. University Hospital Virgen del Rocio, Seville, Spain
                    1. Javier Villadiego
                    1. University of Seville, Seville, Spain
                      1. Miguel Meersmans
                      1. University of Granada, Granada, Spain
                        1. Miguel Perez-Garcia
                        1. University of Granada, Granada, Spain
                          1. David J Brooks
                          1. MRC Cyclotron Unit, Hammersmith Hospital, London, Spain
                            1. Ventura Arjona
                            1. University Hospital Virgen de las Nieves, Granada, Spain
                              1. Jose Lopez-Barneo (lbarneo{at}us.es)
                              1. University of Seville, Seville, Spain

                                Abstract

                                Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line-derived neurotrophic factor (GDNF). The intrastriatal grafting of CB cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal models of Parkinson disease (PD).

                                Objective: We conducted a phase I-II clinical study to assess the feasibility, long-term safety, clinical and neurochemical effects of intrastriatal CB autotransplantation in patients with PD.

                                Methods: Thirteen advanced PD patients underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed presurgically and up to 1-3 years after surgery according to CAPIT and CAPSIT-PD protocols. The primary outcome measure was the change in video-blinded UPDRS III score in off-medication state. Seven patients had 18F-dopa PET scans before and one year after transplantation.

                                Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analyzed patients, maximal at 6-12 months after transplantation (5-74%). Overall, mean improvement at six months was 23%. In the long-term (3 years), 3 of 6 patients still maintained improvement (15-48%). None of the patients developed off-period dyskinesias. The main predictive factors for motor improvement were the histological integrity of the CB and a milder disease severity. We observed a non-significant 5% increase in mean putaminal 18F-dopa uptake but there was an inverse relationship between clinical amelioration and annual decline in putaminal 18F-dopa uptake (r= - 0.829; p= 0.042).

                                Conclusions: CB autotransplantation may induce clinical effects in advanced PD patients which seem partly related to the biological properties of the implanted glomus cells.

                                • GDNF
                                • Parkinson's disease
                                • carotid body
                                • cell therapy
                                • transplantation

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