title: Pilot study of granulocyte-colony stimulating factor for treatment of Alzheimer's disease.
abstract: Human granulocyte colony-stimulating-factor (G-CSF) is widely used for treatment of neutropenia and to mobilize stem/progenitor cells for bone marrow transplantation. In studies of thousands of healthy donor subjects treated with G-CSF to mobilize stem/progenitor cells, the side-effect profile has been reported to be mild and reversible. In pre-clinical studies, G-CSF was reported to improve spatial learning performance and to markedly reduce amyloid deposition in hippocampus and entorhinal cortex in a murine model of Alzheimer's disease (AD). The present study investigated the effects of a five day schedule of G-CSF administration on tolerability, safety, and cognition in eight patients with mild to moderate stage AD. A double-blind placebo control, cross-over design was implemented. Treatment with G-CSF did not result in serious adverse events. The most common and expected side effects were transient increases in white blood cell count, myalgias and diffuse aching that improved with non-steroidal anti-inflammatory medications. Of a battery of cognitive tests administered using the CANTAB computerized system, only the mean paired associate learning (PAL total trials adjusted) was significantly improved at the final visit of the study compared to baseline values (p < 0.05). There were no significant differences in amyloid-β1-42 levels in cerebrospinal fluid measured two weeks after G-CSF and two weeks after placebo treatments. In conclusion, administration of G-CSF in a dosage regimen commonly used for bone marrow donors was well tolerated and safe, and provided a signal of positive change in a hippocampal-dependent task of cognitive performance.
authors: Department of Neurology, College of Medicine, USF Health Byrd Alzheimer's Institute, Tampa, FL, USA. jsramos@health.usf.edu
authors: Juan
authors: J
authors: Sanchez-Ramos
authors: Cynthia
authors: C
authors: Cimino
authors: Ross
authors: R
authors: Avila
authors: Amanda
authors: A
authors: Rowe
authors: Ren
authors: R
authors: Chen
authors: Glenn
authors: G
authors: Whelan
authors: Xiaoyang
authors: X
authors: Lin
authors: Chuanhai
authors: C
authors: Cao
authors: Raj
authors: R
authors: Ashok
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor