The use of antibody engineering to create novel drugs that target N-methyl-D-aspartate receptors.
According to a recent World Health Organization survey, there are over four hundred million people worldwide suffering from mental and neurological disorders; schizophrenia affects some forty-five million people, and unipolar major depression ranked fifth in major causes of disability and death. Clearly it is of the utmost importance to develop new, effective, and safe neuro-pharmaceuticals with this increasing "global burden of disease". To this end, we have developed a strategy of generating monoclonal antibodies that act as modulators of the cell-surface central nervous system receptor-ion channel complexes. In this review we will focus on the generation and characterization of a monoclonal antibody that acts as a partial agonist to the N-methyl-D-aspartate receptor. The creation of peptide mimetics, derived from this monoclonal antibody, that may be useful as cognitive enhancers and protect neurons hypoxic and ischemic insults caused by stroke, will also be discussed.
Moskal
J R
JR
Nyxis Neurotherapies, Inc, and The Chicago Institute for Neurosurgery and Neuroresearch, Chicago, IL 60614, USA. j-moskal@nwu.edu
Yamamoto
H
H
Colley
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D016194:Receptors, N-Methyl-D-Aspartate