title: Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
abstract: OBJECTIVE
  Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
  
  
  METHODS
  This was an open-label, 12-month study in 6 AD patients. Patients were implanted stereotactically with EC-NGF biodelivery devices targeting the basal forebrain. Patients were monitored with respect to safety, tolerability, disease progression and implant functionality.
  
  
  RESULTS
  All patients were implanted successfully with bilateral single or double implants without complications or signs of toxicity. No adverse events were related to NGF or the device. All patients completed the study, including removal of implants at 12 months. Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6 patients were detected.
  
  
  CONCLUSIONS
  This study demonstrates that surgical implantation and removal of EC-NGF biodelivery to the basal forebrain in AD patients is safe, well tolerated and feasible.
authors.affiliation: Departments of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden. maria.eriksdotter.jonhagen @ ki.se
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter-Jönhagen
authors.forename: Bengt
authors.initials: B
authors.lastname: Linderoth
authors.forename: Göran
authors.initials: G
authors.lastname: Lind
authors.forename: Layth
authors.initials: L
authors.lastname: Aladellie
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Vesna
authors.initials: V
authors.lastname: Jelic
authors.forename: Ahmadul
authors.initials: A
authors.lastname: Kadir
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Erik
authors.initials: E
authors.lastname: Sundström
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.forename: Maria
authors.initials: M
authors.lastname: Wiberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Ake
authors.initials: A
authors.lastname: Seiger
authors.forename: Per
authors.initials: P
authors.lastname: Almqvist
authors.forename: Lars
authors.initials: L
authors.lastname: Wahlberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D001344:Autopsy; D001706:Biopsy; D002460:Cell Line; D002540:Cerebral Cortex / Q000473:pathology; D003071:Cognition / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009483:Neuropsychological Tests; D019635:Neurosurgical Procedures; D009538:Nicotine / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D016548:Prosencephalon / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D009414:Nerve Growth Factors; D011978:Receptors, Nicotinic; D009538:Nicotine