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.
- Parkinson's disease
- carotid body
- cell therapy
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