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 protei
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