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Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson's Disease.
Whone, Alan L; Boca, Mihaela; Luz, Matthias; Woolley, Max; Mooney, Lucy; Dharia, Sonali; Broadfoot, Jack; Cronin, David; Schroers, Christian; Barua, Neil U; Longpre, Lara; Barclay, C Lynn; Boiko, Chris; Johnson, Greg A; Fibiger, H Christian; Harrison, Rob; Lewis, Owen; Pritchard, Gemma; Howell, Mike; Irving, Charlie; Johnson, David; Kinch, Suk; Marshall, Christopher; Lawrence, Andrew D; Blinder, Stephan; Sossi, Vesna; Stoessl, A Jon; Skinner, Paul; Mohr, Erich; Gill, Steven S.
Afiliación
  • Whone AL; Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Boca M; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Luz M; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Woolley M; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
  • Mooney L; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Dharia S; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Broadfoot J; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Cronin D; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Schroers C; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Barua NU; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Longpre L; Neurological and Musculoskeletal Sciences Division, North Bristol NHS Trust, Bristol, UK.
  • Barclay CL; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
  • Boiko C; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
  • Johnson GA; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
  • Fibiger HC; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
  • Harrison R; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
  • Lewis O; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Pritchard G; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Howell M; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Irving C; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Johnson D; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Kinch S; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Marshall C; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Lawrence AD; The Wales Research and Diagnostic Positron Emission Tomography Imaging Centre (PETIC), Cardiff University, Cardiff, UK.
  • Blinder S; School of Psychology, Cardiff University, Cardiff, UK.
  • Sossi V; Department of Physics and Astronomy, The University of British Columbia, Vancouver, BC, Canada.
  • Stoessl AJ; Department of Physics and Astronomy, The University of British Columbia, Vancouver, BC, Canada.
  • Skinner P; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
  • Mohr E; Renishaw plc, New Mills, Wotton-under-Edge, Gloucestershire, UK.
  • Gill SS; Med Genesis Therapeutix Inc., Victoria, BC, Canada.
J Parkinsons Dis ; 9(2): 301-313, 2019.
Article en En | MEDLINE | ID: mdl-30829619
BACKGROUND: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [18F]DOPA uptake throughout the entire putamen. OBJECTIVE: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks. METHODS: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson's Disease Rating Scale (UPDRS) motor score. RESULTS: All 41 parent study participants were enrolled. The primary outcome decreased by 26.7±20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6±23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI: -13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week 80 and placebo/GDNF at Week 40 showed significant differences for mean OFF state UPDRS motor (-9.6±6.7 vs. -3.8±4.2 points, p = 0.0108) and activities of daily living score (-6.9±5.5 vs. -1.0±3.7 points, p = 0.0003). No treatment-emergent safety concerns were identified. CONCLUSIONS: The aggregate study results, from the parent and open-label extension suggest that future testing with GDNF will likely require an 80- rather than a 40-week randomized treatment period and/or a higher dose.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Putamen / Factor Neurotrófico Derivado de la Línea Celular Glial Tipo de estudio: Clinical_trials / Guideline / Prognostic_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: J Parkinsons Dis Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Putamen / Factor Neurotrófico Derivado de la Línea Celular Glial Tipo de estudio: Clinical_trials / Guideline / Prognostic_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: J Parkinsons Dis Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos