Researchers have demonstrated that it's not only possible todeliver nerve growth factor (NGF) across the blood brainbarrier (BBB), but also that the NGF exhibits in vivo activity, animportant step in devising means to treat neurologicaldisorders such as Alzheimer's in which the demise of centralcholinergic neurons, which depend on NGF for their survival,may play a role.

Researchers from Alkermes Inc. (NASDAQ:ALKS), Scripps Clinicand Research Foundation, the University of Colorado, andSweden's University of Linkoping reported in today's issue ofScience that NGF, conjugated to an antibody to the transferrinreceptor and injected peripherally, can cross the BBB intomedial forebrain tissue derived from rat embryos that hasbeen transplanted to the anterior chamber of the adult rat eye.

Normally such tissue transplants would not respond toperipherally administered NGF, which doesn't cross the BBB byitself. But it's linked to an antibody to the transferrin receptor,which is found on the brain's capillary epithelial cells, and isresponsible for transporting iron into the brain.

The conjugated NGF also increased the survival and growth ofthe brain tissue transplants compared with controls injectedwith growth factor alone, antibody alone or saline. Histologicalexamination of these tissues showed that the total numbers ofcholinergic and non-cholinergic neurons in the experimentalgroup was higher than for the controls.

The experiments demonstrate that it's possible to deliver"therapeutically relevant concentrations of NGF into the brain,"said Richard Pops, president and chief executive officer ofAlkermes of Cambridge, Mass. "The technology lends itself tomultiple applications, but its real power will come when wemove away from using linkers (between the antibody and thedrug) and just use fusion proteins (to deliver drugs into thebrain)," Pops told BioWorld. "That's something we're workingon now."

-- Jennifer Van Brunt Senior Editor

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