Novel therapeutic targets for autism.
Autism spectrum disorders (ASDs) are pervasive neurodevelopmental disorders, diagnosed in early childhood when acquired skills are lost or the acquisition of new skills becomes delayed. ASDs are associated with varying degrees of dysfunctional communication and social skills, in addition to repetitive and stereotypic behaviors. The diagnosis has increased considerably to approximately one in 180 people, but it is not clear whether this is because of a higher prevalence of the disorder, improved awareness by clinicians or a combination of both. There are no defined mechanisms of pathogenesis or curative therapy presently available. Oxidative stress, overactivation of the hypothalamic-pituitary-adrenal axis and increased gut-blood-brain-barrier permeability might be involved. The scope of this article is to integrate these findings and present the opinion that non-allergic activation of gastrointestinal and brain mast cells could contribute to many of the pathologic findings and provide unique targets for ASD therapy. We make suggestions for new research directives and possible novel therapies from readily available molecules.
Theoharides
Theoharis C
TC
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts Medical Center, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu
Doyle
Robert
R
Francis
Konstantinos
K
Conti
Pio
P
Kalogeromitros
Dimitris
D
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged