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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

The role of mTOR inhibitors in the treatment of autistic symptoms in symptomatic infantile spasms

Principal Investigator

Principal Investigator

Galanopoulou, Aristea

Description

Description

Infantile spasms are the characteristic seizures of infantile epileptic encephalopathies that often lead to cognitive impairment and pose a high risk for the development of autism spectrum disorders. The current therapies for infantile spasms are not always effective and do not always improve long term outcomes. Using a rat model of infantile spasms, the research team has collected preliminary evidence of an early overactivation of the mTOR pathway in cortical regions during the period of spasms and that normalization of mTOR activity with pulse high dose rapamycin (mTOR inhibitor) stops spasms early and has disease modifying effects as it improves cognitive outcomes. This study aims to determine in the multiple hit model of infantile spasms: (a) the optimal protocol for pulse administration of TORC1 vs. dual TORC1/TORC2 inhibitors that succeed in stopping spasms and improving long term cognitive and behavioral outcomes, including autistic-like symptoms; (b) whether disease modification by mTOR inhibitors is via normalization of the late impairment in GABAA receptor signaling pathway; (c) if combined pulse administration of an mTOR inhibitor with vigabatrin, a GABA-enhancing drug, is superior to either monotherapy in treating spasms, seizures and associated cognitive and autistic-like symptoms. The study uses a combination of stereotactic surgeries, video and video-EEG monitoring, neurodevelopmental and behavioral tests, and histology. It is anticipated that this study will clarify some of the molecular mechanisms underlying the disease modifying effects of mTOR inhibitors in the infantile spasms syndrome. Furthermore, it has the potential to provide the basis for the optimization of novel pulse disease modifying therapies for infantile spasms and associated dyscognitive and autistic symptomatology, with an improved tolerability profile compared to chronic mTOR inhibitor administration.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

60000

Current Award Period

Current Award Period

2011-2013

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. 2SE. Launch three studies that target the underlying biological mechanisms of co-occurring conditions with autism, including seizures/epilepsy, sleep disorders, wandering/elopement behavior, and familial autoimmune disorders, by 2012. IACC Recommended Budget: $9,000,000 over 5 years.

Project Link

Project Link

The role of mTOR inhibitors in the treatment of autistic symptoms in symptomatic infantile spasms (External web link)

Institution

Institution

Albert Einstein College of Medicine of Yeshiva University

State/Country

State/Country

New York

Project Number

Project Number

7497

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

The role of mTOR inhibitors in the treatment of autistic symptoms in symptomatic infantile spasms | 0 | 2012 | 7497
The role of mTOR inhibitors in the treatment of autistic symptoms in symptomatic infantile spasms | 0 | 2013 | 7497

 
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