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P2‐064: BENEFICAL PROPERTIES OF A HUMAN PLASMA FRACTION FOR AGE‐RELATED COGNITIVE DISORDERS
Author(s) -
Gallager Ian,
Castro Marian,
Alcantara-Lee Raniel,
Estrada Raul,
Huber Nina,
Kheifets Viktoria,
Czirr Eva,
Minami S Sakura,
Braithwaite Steven P.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.749
Subject(s) - neurogenesis , dentate gyrus , hippocampus , cognitive decline , population , endocrinology , medicine , inflammation , neun , neuroscience , psychology , dementia , disease , environmental health , immunohistochemistry
directly targeting CRH using a high affinity antibody.Methods:Using molecular cloning, vaccination, and hybridoma technology we have successfully generated and purified a monoclonal Anti CRH antibody for use as a potential therapeutic. This antibody is currently being tested as a therapeutic in both mutant APP and tau transgenic mice. Results:A one time intraperitoneal injection of 25 mg/kg of Anti-CRH antibody in mice is able to provide >80% suppression of the corticosterone response to acute restraint stress and is able to reverse the cushingoid phenotype seen in mice that overexpress CRHwithin the brain. This suppression of corticosterone from one dose remains present even four days past injection and possibly much longer. Conclusions:We have generated a high affinity (Kd<1.0E-12) monoclonal CRH antibody that is able to reduce the glucocorticoid response to acute restraint stress by greater than 80%while also maintaining basal glucocorticoid levels in mice. These studies have broad implication for stress-related disorders in addition to AD, and may herald a new class of central nervous system therapies that target neuropeptides using high affinity antibodies.