title: Dose-response comparison of recombinant human nerve growth factor and recombinant human basic fibroblast growth factor in the fimbria fornix model of acute cholinergic degeneration.
abstract: Both nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) have been proposed for the treatment of Alzheimer's disease. This study describes a comparative, dose-response analysis of recombinant human (rh)NGF and rhbFGF in a rat unilateral fimbria-fornix model of acute cholinergic neuronal degeneration. Doses for rhNGF were 0.6, 6, 60, 600 and 1,800 ng/rat/day and for rhbFGF were 600, 1,800, 3,000 and 6,000 ng/rat/day, delivered for 4 weeks. The number of surviving septal cholinergic neurons was evaluated using ChAT immunohistochemistry. In control animals, the number of ChAT-positive neurons remaining on the lesioned side was between 22 and 18% compared to the non-lesioned side. Infusion with either neurotrophic factor increased the number of ChAT-positive neurons on the lesioned side in a dose-dependent manner. The maximal response to rhbFGF peaked at 3,000 ng/rat/day with a cell savings of 47%. However, there was evidence of neuropathological changes associated with rhbFGF. In contrast, rhNGF produced a maximal response with an infusion of 600 ng rhNGF/rat/day and a cell savings of 70% and no evidence of neuropathology, indicating that rhNGF was better tolerated and more efficacious than rhbFGF.
authors.affiliation: Department of Neurosciences, Syntex Discovery Research, Palo Alto, CA 94303, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Emmett
authors.forename: S P
authors.initials: SP
authors.lastname: Aswani
authors.forename: G R
authors.initials: GR
authors.lastname: Stewart
authors.forename: D
authors.initials: D
authors.lastname: Fairchild
authors.forename: R M
authors.initials: RM
authors.lastname: Johnson
mesh_terms: D000110:Acetylcholinesterase; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei
chemical_list: D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D000110:Acetylcholinesterase