Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study
- Adolfo Mínguez-Castellanos1,
- Francisco Escamilla-Sevilla1,
- Gary R Hotton2,
- Juan J Toledo-Aral4,
- Ángel Ortega-Moreno1,
- Simón Méndez-Ferrer4,
- José M Martín-Linares5,
- Majed J Katati5,
- Pablo Mir4,
- Javier Villadiego4,
- Miguel Meersmans6,
- Miguel Pérez-García6,
- David J Brooks3,
- Ventura Arjona5,
- José López-Barneo4
- 1Servicio de Neurología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain
- 2Division of Neuroscience and MRC Clinical Sciences Centre, Imperial College London, UK
- 3Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK
- 4Laboratorio de Investigaciones Biomédicas, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain
- 5Servicio de Neurocirugía, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain
- 6Facultad de Psicología, Universidad de Granada, Granada, Spain
- Correspondence to: Dr José López-Barneo Laboratorio de Investigaciones Biomédicas, Edificio de Laboratorios, 2a planta, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n. 41013 Seville, Spain; Jose.l.Barneo.sspa{at}juntadeandalucia.es
- Received 3 September 2006
- Accepted 26 December 2006
- Revised 16 November 2006
- Published Online First 12 January 2007
Abstract
Background: Carotid body (CB) glomus cells are highly dopaminergic and express the glial cell line derived neurotrophic factor. 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 patients with advanced PD underwent bilateral stereotactic implantation of CB cell aggregates into the striatum. They were assessed before surgery and up to 1–3 years after surgery according to CAPIT (Core Assessment Programme for Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease) protocols. The primary outcome measure was the change in video blinded Unified Parkinson’s Disease Rating Scale III score in the off-medication state. Seven patients had 18F-dopa positron emission tomography scans before and 1 year after transplantation.
Results: Clinical amelioration in the primary outcome measure was observed in 10 of 12 blindly analysed patients, which was maximal at 6–12 months after transplantation (5–74%). Overall, mean improvement at 6 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 patients with advanced PD which seem partly related to the biological properties of the implanted glomus cells.
- CAPIT, Core Assessment Programme for Intracerebral Transplantation
- CAPSIT-PD, Core Assessment Programme for Surgical Interventional Therapies in Parkinson’s Disease
- CB, carotid body
- GDNF, glial cell line derived neurotrophic factor
- PD, Parkinson disease
- PET, positron emission tomography
- TH, tyrosine hydroxylase
- UPDRS, Unified Parkinson’s Disease Rating Scale
Footnotes
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Published Online First 12 January 2007
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Funding: This study was supported by the “Ayuda a la investigación 2000” of the Juan March Foundation and by grants from the Lilly Foundation, Spanish Ministry of Health and the Andalusian Government.
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Competing interests: None.
