Effects of fibroblast growth factor and glial-derived neurotrophic factor on akinesia, F-DOPA uptake and dopamine cells in parkinsonian primates.
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.
Fontan
Aurora
A
Department of Neurology, Fundación Jiménez Díaz, Avda. de Reyes Católicos 2, Madrid 28040, Spain.
Rojo
Ana
A
Sanchez Pernaute
Rosario
R
Hernández
Isabel
I
López
Isabel
I
Castilla
Carlos
C
Sanchez Albisua
Julio
J
Perez Higueras
Antonio
A
Al-Rashid
Imad
I
Rabano
Alberto
A
Gonzalo
Isabel
I
Angeles Mena
Maria
M
Cools
Alex
A
Eshuis
Silvia
S
Maguire
Paul
P
Pruim
Jan
J
Leenders
Klaus
K
Garcia de Yebenes
Justo
J
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
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