title: Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy.
abstract: We report on the clinical outcome of a first case of intracranial infusion of nerve growth factor (NGF) to an Alzheimer patient. The therapeutic attempt is based on animal research showing that NGF stimulates central cholinergic neurons of the type known to be lost during the development of Alzheimer's disease (AD). Furthermore, our own previous clinical experience of infusing NGF to support the survival of intracranially transplanted adrenal chromaffin cells to Parkinsonian patients indicate this approach to be technically possible and safe and clinically of significant potential. Our first case was a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF over three months resulted in a marked transient increase in uptake and binding of [11C]nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF infusion, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects of the NGF infusion were found. The results of this single case indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.
authors.affiliation: Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Seiger
authors.forename: A
authors.initials: A
authors.lastname: Nordberg
authors.forename: H
authors.initials: H
authors.lastname: von Holst
authors.forename: L
authors.initials: L
authors.lastname: Bäckman
authors.forename: T
authors.initials: T
authors.lastname: Ebendal
authors.forename: I
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: K
authors.initials: K
authors.lastname: Amberla
authors.forename: P
authors.initials: P
authors.lastname: Hartvig
authors.forename: A
authors.initials: A
authors.lastname: Herlitz
authors.forename: A
authors.initials: A
authors.lastname: Lilja
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D001706:Biopsy; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000502:physiology; D009483:Neuropsychological Tests; D014055:Tomography, Emission-Computed
chemical_list: D009414:Nerve Growth Factors