ArmaGen Re-engineers Erythropoietin for Brain Penetration
LOS ANGELES, July 16 /PRNewswire/ -- Human erythropoietin (EPO)
is a potent neuroprotective agent for multiple brain disorders,
including stroke, brain and spinal cord injury, and Parkinson's
disease. However, EPO drug development for the brain is limited,
because EPO does not cross the blood-brain barrier (BBB). In acute
stroke or brain injury, the BBB is intact in the early hours after
the insult when neuroprotection is still possible. Therefore, large
molecule biopharmaceuticals such as EPO must be re-engineered to
enable BBB transport. ArmaGen Technologies has developed the BBB
molecular Trojan horse platform technology for solving the BBB drug
delivery problem, and has used this technology to create a brain
penetrating form of human EPO. ArmaGen® has successfully
re-engineered human EPO as an IgG fusion protein that penetrates
the brain following intravenous (IV) administration. Human EPO is
fused to a genetically engineered monoclonal antibody (MAb) to the
human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan
horse to ferry the EPO across the BBB via transport on the
endogenous BBB insulin receptor. The HIRMAb-EPO fusion protein is a
dual receptor specific protein with low nM binding constants for
both the human EPO receptor and the human insulin receptor. The
HIRMAb part of the HIRMAb-EPO fusion protein cross-reacts with the
Rhesus monkey insulin receptor. Therefore, brain penetration of the
HIRMAb-EPO fusion protein was demonstrated in vivo in the adult
Rhesus monkey following IV administration. EPO alone was shown not
to cross the primate BBB. The brain uptake of the HIRMAb-EPO fusion
protein in the Rhesus monkey is high, 2% injected dose/brain, and
comparable to the brain uptake of small molecules. The plasma
pharmacokinetics (PK) of the HIRMAb-EPO fusion protein differs
markedly from the PK of EPO, which minimizes any effect of the
fusion protein on erythropoiesis. EPO-driven neuroprotection in
human brain disorders is now possible with systemic administration
of the HIRMAb-EPO fusion protein at doses that have minimal effects
on erythropoiesis. The work is published in the June, 2010 issue of
the Journal of Pharmacology and Experimental Therapeutics.
About ArmaGen® Technologies
ArmaGen® Technologies is a privately-held biotechnology
company developing therapeutic products for the central nervous
system. ArmaGen® re-engineers recombinant proteins to enable
transport across the BBB. With ArmaGen®'s proprietary molecular
Trojan horse technology, any recombinant protein can be
re-engineered as a new brain penetrating neuropharmaceutical. For
more information on ArmaGen® Technologies, visit the Company's
Web site at www.armagen.com.
Source: ArmaGen Technologies
CONTACT: Paul Lee of ArmaGen Technologies, +1-310-917-1275
Web Site: http://www.armagen.com/
Posted: July 2010
