Accession Number : AD1003166


Title :   Dual Modulators of GABA-A and Alpha 7 Nicotinic Receptors for Treating Autism


Descriptive Note : Technical Report,05 Aug 2013,04 Aug 2015


Corporate Author : University of California Irvine Irvine United States


Personal Author(s) : Gee,Kelvin W


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1003166.pdf


Report Date : 01 Oct 2015


Pagination or Media Count : 19


Abstract : Autism spectrum disorder (ASD) is a disease of development characterized by three core behavioral symptoms including difficulties in social interaction, verbal and nonverbal communication and repetitive/stereotypical behaviors. The Department of Health and Human Services states that the increasing prevalence of ASDs, currently estimated at 1 in 88 children, is a national health emergency. Yet there are no drugs for the treatment of these core deficits or associated neurological/medical symptoms such as epilepsy and anxiety. Consequently, ASD is a dire unmet medical need. The greatest challenge is to find a drug with a broad range of activity that will treat both the core symptoms and associated difficulties (i.e., epilepsy, anxiety, disrupted learning and memory). The objective of our project is to fulfill this profound need for drugs that can do exactly that by studying a new class of compounds that will simultaneously enhance the function of two neurotransmitters in the brain known as -aminobutyric acid (GABA) and acetylcholine (ACh). GABA acting through GABAA receptors (GABAARs) is responsible for reducing the activity of nerve cells in the brain that may be overstimulated in ASD and thus contributes to the three core symptoms and the anxiety and epilepsy that sometimes occur in ASD. ACh acting through a7 nicotinic receptors (a7 nAChRs) control the activity of nerve cells in the brain that may be under-stimulated in ASD which may underlie the difficulties in learning and memory observed in ASD. This approach may provide the basis for the design of an innovative series of drugs acting simultaneously at both receptors and will thus represent the first attempt at treating the core and significant comorbidities of ASD with a single drug.


Descriptors :   anxiety , brain , children , NERVOUS SYSTEM DISEASES , epilepsy , NEUROTRANSMITTERS , learning , MEMORY(PSYCHOLOGY) , HUMAN RELATIONS , RECEPTOR SITES(PHYSIOLOGY) , PHARMACOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE