Methods and compositions for treating smith-magenis syndrome
View Patent ↗The present invention is based on the finding that subanesthetic doses of N-methyl-D-aspartate (NMDA) receptor antagonists alleviate social interaction deficits associated with behavioral disorders, such as Smith-Magenis Syndrome (SMS). The invention therefore provides methods and compositions for treating SMS. Also provided are methods of selecting NMDA receptor agonists useful in alleviating social interaction deficits associated with such behavioral disorders.
1 . A method for alleviating a social interaction deficit in a subject with a neurodegenerative disease or behavioral disorder, the neurodegenerative disease or behavioral disorder associated with lethal giant larvae (Lgl1) induced increase in synapses in a population of neurons in the subject's brain, comprising administering to the subject a subanesthetic amount of an N-methyl-D-aspartate (NMDA) receptor antagonist;
wherein the NMDA receptor antagonist is selected from the group consisting of ketamine, memantine, dizocilpine (MK-801), dextromethorphan (DXM), phencyclidine (PCP), methoxetamine (MXE), and nitrous oxide (N 2 O);
wherein the neurodegenerative disease or behavioral disorder is selected from the group consisting of Smith-Magenis Syndrome (SMS) and attention deficit hyperactivity disorder (ADHD).
2 . The method of claim 1 , wherein the NMDA receptor antagonist increases the AMPA/NMDA ratio in the neurons.
3 . The method of claim 1 , wherein the method further comprises contacting the population of neurons with an atypical protein kinase c (aPKC) inhibitor comprising Lgl1 protein.
4 . A method of managing or treating a social interaction deficit in a subject with a neurodegenerative disease or behavioral disorder in a subject, comprising administering to the subject a subanesthetic amount of an N-methyl-D-aspartate (NMDA) receptor antagonist;
wherein the NMDA receptor antagonist is selected from the group consisting of ketamine, memantine, dizocilpine (MK-801), dextromethorphan (DXM), phencyclidine (PCP), methoxetamine (MXE), and nitrous oxide (N 2 O);
wherein the neurodegenerative disease or behavioral disorder is selected from the group consisting of Smith-Magenis Syndrome (SMS) and attention deficit hyperactivity disorder (ADHD).
5 . The method of claim 4 , wherein the method further comprises administering to the subject an atypical protein kinase c (aPKC) inhibitor comprising Lgl1 protein.