PMID- 15717063
OWN - NLM
STAT- MEDLINE
DCOM- 20050823
LR  - 20181113
IS  - 1545-5343 (Print)
IS  - 1545-5351 (Electronic)
IS  - 1545-5343 (Linking)
VI  - 2
IP  - 1
DP  - 2005 Jan
TI  - Neuroprotection in experimental stroke with targeted neurotrophins.
PG  - 120-8
AB  - More than 30 neurotrophins have been identified, and many of them have 
      neuroprotective effects in brain ischemia or injury. However, all the clinical 
      trials with several neurotrophins for the treatment of acute ischemic stroke or 
      neurodegenerative diseases have failed so far, primarily because of their poor 
      blood-brain barrier (BBB) permeability. This article is an overview of recent 
      progress in the research focused on BBB targeted neurotrophins using a chimeric 
      peptide approach, in which antitransferrin receptor antibody was used as a BBB 
      delivery vector, and neurotrophin peptide was conjugated to the antibody via the 
      avidin/biotin technology. Vasoactive intestinal peptide was the first model 
      chimeric peptide to show an enhanced CNS effect after noninvasive peripheral 
      administration. Brain-derived neurotrophic factor (BDNF) chimeric peptide was 
      neuroprotective in rats subjected to transient forebrain ischemia, permanent 
      focal ischemia, or transient focal ischemia. Delayed treatments with the BDNF 
      chimeric peptide showed an effective time window of 1-2 h after ischemia. Basic 
      FGF chimeric peptide was highly effective in the reduction of infarct volume in 
      the rat model of permanent focal ischemia, with lowest effective dose of 1 mug 
      per rat. Future studies in this exciting area include genetically engineered 
      fusion proteins or humanized antibodies for BBB drug targeting with less 
      immunogenicity and reduced working burden in the chemical conjugation, the use of 
      antihuman insulin receptor antibody for higher BBB delivery efficiency, and 
      combination therapies using chimeric neurotrophins plus other neuroprotectants to 
      achieve additive or synergistic effects.
FAU - Wu, Dafang
AU  - Wu D
AD  - Department of Radiology, Wayne State University School of Medicine, Children's 
      Hospital of Michigan, PET Center, Detroit, Michigan 48201, USA. dwu@pet.wayne.edu
LA  - eng
GR  - R01 NS034698/NS/NINDS NIH HHS/United States
GR  - NS34698/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - NeuroRx
JT  - NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics
JID - 101189456
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 37221-79-7 (Vasoactive Intestinal Peptide)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier
MH  - Brain Ischemia/drug therapy
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/therapeutic use
MH  - Clinical Trials as Topic
MH  - Fibroblast Growth Factor 2/administration & dosage/therapeutic use
MH  - Humans
MH  - Nerve Growth Factors/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Neuroprotective Agents/administration & dosage/pharmacokinetics/*therapeutic use
MH  - Receptors, Transferrin/drug effects
MH  - Recombinant Fusion Proteins/pharmacokinetics
MH  - Stroke/*drug therapy
MH  - Thrombolytic Therapy
MH  - Vasoactive Intestinal Peptide/administration & dosage/pharmacology
PMC - PMC539332
EDAT- 2005/02/18 09:00
MHDA- 2005/08/24 09:00
PMCR- 2005/07/01
CRDT- 2005/02/18 09:00
PHST- 2005/02/18 09:00 [pubmed]
PHST- 2005/08/24 09:00 [medline]
PHST- 2005/02/18 09:00 [entrez]
PHST- 2005/07/01 00:00 [pmc-release]
AID - S1545-5343(06)70028-1 [pii]
AID - 1188411 [pii]
AID - 10.1602/neurorx.2.1.120 [doi]
PST - ppublish
SO  - NeuroRx. 2005 Jan;2(1):120-8. doi: 10.1602/neurorx.2.1.120.