Autoimmune-Induced Glutamatergic Receptor Dysfunction Methods and Treatments

Abstract

This invention provides a method of enhancing NMDAR-mediated neurotransmission in a disease associated with NMDAR antibody production, said method comprising administering an NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof to said subject. This invention also provides a method of mitigating the severity of, mitigating the pathogenesis of, lowering the incidence of or treating a disease associated with NMDAR antibody production, said method comprising administering an agent, which is an NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof to said subject.

1 . A method of enhancing NMDAR-mediated neurotransmission in a disease associated with NMDAR antibody production, said method comprising administering an NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof to said subject. 
     
     
         2 . A method of mitigating the severity of, mitigating the pathogenesis of, lowering the incidence of or treating a disease associated with NMDAR antibody production, said method comprising administering an agent, which is a n NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof to said subject. 
     
     
         3 . The method of  claim 1 , wherein said disease associated with NMDAR antibody production is paraneoplastic autoimmune encephalitis. 
     
     
         4 . The method of  claim 1 , wherein said disease associated with NMDAR antibody production is non-paraneoplastic autoimmune encephalitis. 
     
     
         5 . The method of  claim 1 , wherein said disease associated with NMDAR antibody production is anti-NMDAR encephalitis. 
     
     
         6 . The method of  claim 5 , wherein said NMDA receptor-associated encephalitis is associated with occult tumor. 
     
     
         7 . The method of  claim 6 , wherein said tumor is an ovarian teratoma. 
     
     
         8 . The method of  claim 6 , wherein said method further comprises the step of removing said tumor, providing immunotherapy or a combination thereof. 
     
     
         9 . The method of  claim 1 , wherein said agent is glycine (GLY), D-serine, D-cycloserine (DSR), or a combination thereof. 
     
     
         10 . The method of  claim 1 , wherein said agent is D-serine and is administered at a dosage of 30-60 mg/kg/d. 
     
     
         11 . The method of  claim 1 , wherein said agent is Glycine and is administered at a dosage of 40-60 g/d. 
     
     
         12 . The method of  claim 1 , wherein said agent is D-cycloserine and is administered at a dosage of 250-1000 mg/d. 
     
     
         13 . The method of  claim 1 , wherein said agent is Bitopertin and is administered at a dosage of 10-40 mg/d. 
     
     
         14 . The method of  claim 1 , wherein said agent is Benzoic acid and is administered at a dosage of 500-2000 mg/d. 
     
     
         15 . The method of  claim 1 , wherein said method is utilized during an acute stage of a disease associated with NMDAR antibody production. 
     
     
         16 . The method of  claim 1 , wherein said method is utilized during a rehabilitational stage of a disease associated with NMDAR antibody production. 
     
     
         17 . The method of  claim 1 , wherein said method further comprises treating said subject with an adjunct cognitive treatment regimen.