title: Effects of fibroblast growth factor and glial-derived neurotrophic factor on akinesia, F-DOPA uptake and dopamine cells in parkinsonian primates.
abstract: Parkinson's disease (PD) is a common neurodegenerative disorder that produces progressive disability despite symptomatic treatment. Several strategies, including stereotaxic brain lesions, deep brain stimulation, transplants of dopamine cells and administration of neurotrophic factors, have been proposed to improve efficacy and to counteract the progression of the disease. We here report the effects of repetitive intracerebral infusion of basic fibroblast growth factor (bFGF) and glial-derived neurotrophic factor, up to 1 year, in Cynomolgus monkeys with long standing asymmetric parkinsonism produced by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The treatment with neurotrophic factors was initiated when the parkinsonian deficits were stable, 6 months after the administration of MPTP. The evaluation of the response to the neurotrophic factors was performed by blind observers using: clinical scales that measured global motor deficit, motor ability in both hands, apomorphine-induced rotation, determination of the levels of monoamine metabolites in cerebrospinal fluid, and 6-F18-fluoro-l-DOPA (F-DOPA) uptake in the striatum and histology. Both factors, but bFGF more so, improve motor behavior, dopamine metabolism, striatal F-DOPA uptake, and the number of dopamine neurons. The procedure is well tolerated and provides a strong background for efficacy and safety of this treatment in patients with PD.
authors.affiliation: Department of Neurology, Fundación Jiménez Díaz, Avda. de Reyes Católicos 2, Madrid 28040, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Fontan
authors.forename: Ana
authors.initials: A
authors.lastname: Rojo
authors.forename: Rosario
authors.initials: R
authors.lastname: Sanchez Pernaute
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.forename: Isabel
authors.initials: I
authors.lastname: López
authors.forename: Carlos
authors.initials: C
authors.lastname: Castilla
authors.forename: Julio
authors.initials: J
authors.lastname: Sanchez Albisua
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez Higueras
authors.forename: Imad
authors.initials: I
authors.lastname: Al-Rashid
authors.forename: Alberto
authors.initials: A
authors.lastname: Rabano
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonzalo
authors.forename: Maria
authors.initials: M
authors.lastname: Angeles Mena
authors.forename: Alex
authors.initials: A
authors.lastname: Cools
authors.forename: Silvia
authors.initials: S
authors.lastname: Eshuis
authors.forename: Paul
authors.initials: P
authors.lastname: Maguire
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.forename: Klaus
authors.initials: K
authors.lastname: Leenders
authors.forename: Justo
authors.initials: J
authors.lastname: Garcia de Yebenes
mesh_terms: D000818:Animals; D002452:Cell Count; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004298:Dopamine / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005462:Fluorine Radioisotopes; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008252:Macaca fascicularis; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D005462:Fluorine Radioisotopes; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine