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

Project Title

Project Title

Role of intracellular mGluR5 in fragile X syndrome and autism

Principal Investigator

Principal Investigator

O'Malley, Karen

Description

Description

The most commonly inherited form of autism involves the gene encoding fragile X mental retardation protein (FMRP). Loss of FMRP function disrupts signaling between neurons, leading to widespread brain abnormalities and mental retardation. Normally, FMRP is balanced by mGluR5, an important receptor in the brain that is involved in learning and memory. Without normal FMRP, this balance is lost, leaving mGluR5 function unopposed. Early results from a clinical trial suggest that children with fragile X syndrome can be helped by drugs that inhibit mGluR5 activity. Karen O'Malley and her colleagues have shown that up to 90 percent of mGluR5 receptors are found inside neurons, where they can regulate different signaling systems. Stimulation of this mGluR5 induces long, sustained calcium increases, leading to the modification of proteins involved in learning and memory. In contrast, mGluR5 stimulation on the outside of the neuron triggers rapid, transient calcium signals. Most studies so far have used drugs that cannot enter the cell. O'Malley and colleagues aim to re-examine mGluR5 pathways using molecules that specifically activate the intracellular receptors. Using pharmacological, molecular and genetic tools, O'Malley and colleagues plan to test whether intracellular mGluR5 responses underlie fundamental properties of learning and memory, such as protein synthesis, increased FMRP, and increased branching of neurons. These properties will also be examined in animals lacking mGluR5 and FMRP. Given its role in fragile X syndrome and autism, mGluR5 makes an attractive target for drug discovery. Future studies targeting drugs specifically to the cell surface or to intracellular receptors might lead to new therapeutic tools for fragile X and autism.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

75000

Current Award Period

Current Award Period

2010-2012

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.

Project Link

Project Link

Role of intracellular mGluR5 in fragile X syndrome and autism (External web link)

Institution

Institution

Washington University in St. Louis

State/Country

State/Country

Missouri

Project Number

Project Number

177222

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Role of intracellular mGluR5 in fragile X syndrome and autism | 75000 | 2010 | 177222
Role of intracellular mGluR5 in fragile X syndrome and autism | 150000 | 2011 | 177222

 
Back to Top