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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Nicotinic cholinergic modulation as a novel treatment strategy for aggression associated with autism

Principal Investigator

Principal Investigator

Lewis, Alan

Description

Description

Aggression is highly comorbid with autism spectrum disorder (ASD) and is a strong predictor of negative outcomes for patients and families. Current pharmacological options for aggression are of limited efficacy for many and can result in further morbidity. Better understanding of the neurobiology underlying aggression in ASD and novel pharmacological treatment strategies rationally derived from these mechanisms are required to solve this critical problem. Genetic, neuropathological, and animal model studies have found abnormalities of the nicotinic acetylcholine receptor (nAChR) system in brains of people with ASD, and nAChRs influence the properties of essentially all major neurotransmitter systems. The nAChR agonist nicotine reduces aggression in multiple animal models, and our preliminary data suggests its effect is via activation of the α7 receptor. CHRNA7, the gene for α7, is deleted in 15q13.3 microdeletion syndrome, which phenotypically can include ASD and aggression. This project thus hypothesizes that modulation of nAChR signaling might be a novel treatment strategy for aggression in ASD. This hypothesis will be tested by 1) identifying the neurocircuitry and pharmacology underlying nicotine’s anti-aggressive effect in mouse models of aggression and ASD, and 2) determining the efficacy of transdermal nicotine for aggression in ASD in a pilot clinical trial.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

59700

Current Award Period

Current Award Period

2015-2018

Strategic Plan Question

Strategic Plan Question

Question 4: Which Treatments And Interventions Will Help?

Strategic Plan Objective

Strategic Plan Objective

Yellow dot: Objective has some degree of funding, but less than the recommended amount. 4SA. Support at least three randomized controlled trials that address co-occurring medical conditions associated with ASD by 2010. IACC Recommended Budget: $13,400,000 over 3 years.

Project Link

Project Link

Nicotinic cholinergic modulation as a novel treatment strategy for aggression associated with autism (External web link)

Institution

Institution

Yale University

State/Country

State/Country

Connecticut

Project Number

Project Number

9699

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

N/A

 
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