Thursday, May 23, 2013
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Improved safety for blood
brain barrier (BBB)-penetrating antibodies
Mouse studies suggest
bispecific antibodies that cross the BBB can be made safer by modifying the
effector portion of the antibody. Previous studies identified a
BBB-penetrant, bispecific mAb against the Alzheimer's disease (AD) target b-site APP-cleaving enzyme 1 (BACE1)
receptor protein 1 (TFRC;
In mice, a variant of the mAb that was unable to bind the Fc g-receptor (FCGR)
showed BBB penetration levels comparable to those of the original mAb. In
mice, the mAb variant showed a better toxicity profile than the original mAb.
Next steps include humanizing the FCGR binding-compromised mAb and conducting
further preclinical development.
Published online May 23, 2013
Patent pending; licensing
Couch, J.A. et al. Sci.
Transl. Med.; published online May 1, 2013;
Contact: Ryan J. Watts, Genentech Inc., South San Francisco, Calif.
Contact: Mark S. Dennis, same affiliation as above
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