Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS

Journal Article · Fri Dec 18 00:00:00 EST 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.10.083· OSTI ID:22199923

Li, Jianhong; Chian, Ru-Ju; Ay, Ilknur; Kashi, Brenda B.; Celia, Samuel A.; Tamrazian, Eric ^[1]; Pepinsky, R. Blake ^[2]; Fishman, Paul S. ^[3]; Brown, Robert H. ^[1]

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1. Cecil B. Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129 (United States)
2. BiogenIdec, Inc., 14 Cambridge Center, Cambridge, MA 02142 (United States)
3. Research Service, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201 (United States)

With a view toward improving delivery of exogenous glial cell line-derived neurotrophic factor (GDNF) to CNS motor neurons in vivo, we evaluated the bioavailability and pharmacological activity of a recombinant GDNF:tetanus toxin C-fragment fusion protein in mouse CNS. Following intramuscular injection, GDNF:TTC but not recombinant GDNF (rGDNF) produced strong GDNF immunostaining within ventral horn cells of the spinal cord. Intrathecal infusion of GDNF:TTC resulted in tissue concentrations of GDNF in lumbar spinal cord that were at least 150-fold higher than those in mice treated with rGDNF. While levels of immunoreactive choline acetyltransferase and GFR{alpha}-1 in lumbar cord were not altered significantly by intrathecal infusion of rGNDF, GDNF:TTC, or TTC, only rGDNF and GDNF:TTC caused significant weight loss following intracerebroventricular infusion. These studies indicate that insect cell-derived GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves delivery of GDNF to spinal cord following intramuscular- or intrathecal administration.

• OSTI ID: 22199923
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 390, Issue 3; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
CHOLINE
CONCENTRATION RATIO
IN VIVO
INFUSION
INSECTS
INTRAMUSCULAR INJECTION
MICE
NERVE CELLS
PROTEINS
SPINAL CORD
TETANUS
TOXINS