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Conference Program
 
Fragile X and Autism-Related Disorders
Progress and Struggles in Translating Scientific Advances into Human Therapy
June 1-6, 2014
Mount Snow Resort
West Dover, VT

Related Meeting Information
The Fragile X and Autism-Related Disorders Gordon Research Conference was held in conjunction with the Fragile X and Autism-Related Disorders Gordon Research Seminar. Please refer to the Fragile X and Autism-Related Disorders GRS web page for more information.

Fragile X syndrome (FXS) is the most common form of inherited intellectual deficiency and the most frequent single gene cause of autism, affecting 1 in 5,000 males and a lesser number of females. Autism spectrum disorders (ASD) occur in up to 2/3 of males and 1/3 of females with FXS. The Fragile X gene (FMR1) was cloned in 1991 and since then a large field has grown with more than a hundred labs using techniques from biochemistry through genetics to model organisms to elucidate the functions of the FMR1 protein (FMRP). FMRP is primarily a polyribosome-associated protein that regulates the translation of a set of messages highly enriched for synaptic proteins. In addition to regulating translation in the cell body FMRP has been found to interact with and accompany a crucial subset of messages to the sites of neural communication (the synapses). At those synapses, FMRP is a critical switch that mediates changes in local protein expression in response to neural activity, causing synapses to strengthen or weaken in response to experience. Specific signaling mechanisms have been proposed to mediate this control at the synapse, including group I metabotropic glutamate receptors. In addition, a great deal has been discovered about the effects of loss of FMRP function on dendritic spine dynamics, and altered synaptic transmission in various brain areas, and understanding has been extended to the impact of altered synaptic responses on circuit function and learning in model organisms. Functions for FMRP other than its role as a translational regulator have also recently come to light. Generalizing these findings to human patients suggests that when FMRP is missing synapses are less able to change with experience and learning is greatly reduced.

It has become clear that in addition to the clinical overlap between FXS and autism spectrum disorders (ASD), there is likely substantial overlap in the molecular pathology of the two disorders. As such, molecular defects known to cause ASD and other neurodevelopmental disorders (NDD) may involve other proteins in the signaling pathways that are regulated by or regulate FMRP activity, may involve proteins whose translation is regulated by FMRP, or may involve defects in neurotransmitter systems shown to be dysregulated in FXS models. Molecules aimed at targets in such pathways are now being developed and tested in academic laboratories and through the pharmaceutical industry, in order to offer effective drug therapies for patients with FXS. It is expected that many of these targeted treatments will have therapeutic overlap in subsets of individuals with ASD or NDD.

This conference will bring together leading scientists and clinicians in the Fragile X, ASD, and NDD fields, particularly those working on forms of ASD/NDD with dysfunctions in molecular pathways that overlap those implicated in FXS. Topics will include the latest developments in genetics of ASDs and related diseases, FMRP function and its regulation, the overlap between the diseases at the molecular and genetic level, model system characterizations, dendritic spine dynamics and synaptic plasticity studies, outcome measures, and translation to treatment trials in humans with FXS and ASD/NDD. The conference is expected to accelerate the pace of bench-to-bedside translational research to bring important targeted treatments to individuals with FXS and ASD-related disorders.


Contributors

SUNDAY
2:00 pm - 9:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmKeynote Session
Discussion Leader: Elizabeth Berry-Kravis (Rush University Medical Center)
7:40 pm - 7:50 pmJennifer Darnell, Michael Tranfaglia, and Liz Berry-Kravis (Meeting Chair, Vice Chair and Chair Emeritus)
"Welcoming Remarks"
7:50 pm - 8:35 pmDavid L. Nelson (Baylor College of Medicine)
"Insights from Fragile X Syndrome, the Leading Single Gene Cause of Autism"
8:35 pm - 8:40 pmDiscussion
8:40 pm - 9:25 pmGeorge Apostol (Novartis)
"Clinical Trials in Rare Diseases: Brief Guide to Navigating Uncharted Waters"
9:25 pm - 9:30 pmDiscussion
MONDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmThe Molecular Basis of Autism and Fragile X Syndrome: Key Players at the DNA, RNA and Protein Level
Discussion Leader: David L. Nelson (Baylor College of Medicine)
9:00 am - 9:30 amBrian O'Roak (Oregon Health & Science University)
"Unlocking Autism: Novel Genes and Pathways Identified Using Genomic Approaches"
9:30 am - 9:40 amDiscussion
9:40 am - 10:10 amNeelroop Parikshak (UCLA)
"Gene Expression from Cortex in Neurotypical Development and Autism - Insights into the Molecular Underpinnings of ASD"
10:10 am - 10:20 amDiscussion
10:20 am - 10:50 amCoffee Break
10:50 am - 11:20 amJosh Suhl (Emory University)
"Not Just Triplet Repeats: Conventional Mutations of FMR1"
11:20 am - 11:30 amDiscussion
11:30 am - 12:00 pmJoel Richter (University of Massachussetts Medical School)
"Rescuing Fragile X Through Translational Homeostasis"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmThe Cellular Basis of Cognition and Behavior
Discussion Leader: Len Kaczmarek (Yale University)
7:30 pm - 8:00 pmCarlos Portera-Cailliau (UCLA)
"Circuit-Level Dysfunction in the Neocortex of Fmr1 Knockout Mice"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmKimberly Huber (University of Texas, Southwestern)
"Regulation of Homer Scaffolds in Fragile X Syndrome"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmPeter Kind (University of Edinburgh)
"Convergence of Hippocampal Pathophysiology in Fmr1-/y and Related Mouse Models of ASD/ID"
9:20 pm - 9:30 pmDiscussion
TUESDAY
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmNew Approaches
Discussion Leader: Eric Klann (NYU)
9:00 am - 9:30 amXinyu Zhao (University of Wisconsin)
"Using Stem Cells as Model Systems to Investigate the Functions of Fragile X Proteins"
9:30 am - 9:40 amDiscussion
9:40 am - 10:10 amMark Zylka (University of North Carolina, Chapel Hill)
"Topoisomerases and Synaptic Function"
10:10 am - 10:20 amDiscussion
10:20 am - 10:50 amCoffee Break
10:50 am - 11:20 amGul Dolen (John's Hopkins)
"Social Reward: Basic Mechanisms and Autism Pathogenesis"
11:20 am - 11:30 amDiscussion
11:30 am - 12:00 pmLen Kaczmarek (Yale)
"Slack Channels, FMRP and Developmental Delay; A Tale of Too Much Molecular Cooperation"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmClinical Trials of Targeted Treatments
Discussion Leader: Elizabeth Berry-Kravis (Rush University Medical Center)
7:30 pm - 8:00 pmJeffrey Neul (Baylor College of Medicine)
"Advances in Treatment in Rett Syndrome"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmMike Ufer (Novartis)
"Pediatric Development of mGluR Antagonists in Patients with FXS: Focus on Mavoglurant (AFQ056")"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmJonathan Rubin (Alcobra Ltd)
"The Development of Metadoxine Extended Release (MDX), a Novel GABA/Glutamate Modulating Agent, for Cognitive Impairment in Fragile X"
9:20 pm - 9:30 pmDiscussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDysregulated Protein Expression and Neurologic Disease
Discussion Leader: Joel Richter (University of Massachussetts Medical School)
9:00 am - 9:30 amEric Klann (New York University)
"Targeting Translational Control in FXS and ASD"
9:30 am - 9:40 amDiscussion
9:40 am - 10:10 amDamon Page (The Scripps Research Institute)
"The Influence of Pten Signaling on Brain Growth Dynamics"
10:10 am - 10:20 amDiscussion
10:20 am - 10:50 amCoffee Break
10:50 am - 11:20 amMustafa Sahin (Harvard Children's Hospital)
"Dissecting the Neural Circuitry of ASD Using Tuberous Sclerosis"
11:20 am - 11:30 amDiscussion
11:30 am - 12:00 pmCristina Alberini (New York University)
"IGF-II Treatment Enhances Memories and Rescues Autistic Phenotypes"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
7:30 pm - 9:30 pmSynaptic Plasticity and Circuits
Discussion Leader: Peter Kind (University of Edinburgh)
7:30 pm - 8:00 pmPavel Osten (Cold Spring Harbor Labs)
"Social Behavior-Evoked Brain Activation Mapped by STP Tomography"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmVitaly Klyachko (Washington University, St. Louis)
"Role of Channelopathies in Excitability Defects in Fragile X Syndrome"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmAndrés Ozaita (Universitat Pompeu Fabra, Barcelona)
"The Endocannabinoid System as a Therapeutic Target for Fragile X Syndrome"
9:20 pm - 9:30 pmDiscussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmChallenges in Translating Results from Models to Human Therapy
Discussion Leader: George Apostol (Novartis)
9:00 am - 9:40 amMichael Tranfaglia (FRAXA)
"Enhanced Clinical Trials in Fragile X"
9:40 am - 9:50 amDiscussion
9:50 am - 10:30 amDavid Hessl (University of California, Davis)
"Cognitive Outcome Measures in Intellectual Disabilities: Limitations, Solutions, and Future Plans"
10:30 am - 10:40 amDiscussion
10:40 am - 11:10 amCoffee Break
11:10 am - 11:50 amElizabeth Berry-Kravis (Rush University Medical Center)
"Translation of Targeted Treatments in Fragile X: Where Have We Been? What Have We Learned? Where Are We Going?"
11:50 am - 12:00 pmDiscussion
12:00 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmRegulation of Gene Expression at the Level of Transcription and Translation in FXS and Autism
Discussion Leader: Michael Tranfaglia (FRAXA)
7:30 pm - 8:00 pmFrank Kooy (University of Antwerp, Belgium)
"The Transcription Factor ADNP Links the BAF (SWI/SNF) Complexes with Autism"
8:00 pm - 8:10 pmDiscussion
8:10 pm - 8:40 pmGary Bassell (Emory University)
"Multiple Strategies for Targeted Reduction of PI3K Signaling Rescue Molecular, Cellular and Cognitive Phenotypes in Animal Models of Fragile X Syndrome"
8:40 pm - 8:50 pmDiscussion
8:50 pm - 9:20 pmSally Till (University of Edinburgh)
"Conservation of Hippocampal Pathophysiology in Mammalian Models of FXS"
9:20 pm - 9:30 pmDiscussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

 
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