Fragile X and Autism-related Disorders

Fragile X syndrome (FXS) is the most common form of inherited intellectual deficiency and the most common identifiable 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 roughly one hundred labs using techniques from biochemistry through genetics to model organisms to elucidate the functions of the FMR1 protein (FMRP). FMR1 gene homologs have been found in Drosophila and mice, and useful null mutant models generated in both. FMRP has been found to be involved in the regulation of specific messenger RNA transport, localization and expression in neurons. Briefly put, FMRP is thought to bind and help transport a crucial subset of messages to the sites of neural action (the synapses). At those synapses, FMRP is a critical switch that mediates changes in local protein expression in response to neural activity - in effect causing the synapses to strengthen or weaken as required in response to experience. When FMRP is reduced or missing in an affected person, the synapses are much less able to change with experience and learning is greatly reduced. More recently, specific signaling mechanisms have been proposed to mediate this control at the synapse, via a specific set of Gq-linked (neurotransmitter) receptors, including group I mGluRs (metabotropic glutamate receptors). It has become clear that in addition to clinical overlap between FXS and ASD, there is likely substantial overlap in the molecular pathology of the two disorders. As such, molecular defects known to cause ASD may involve other proteins in the signaling pathways that are regulated by or regulate FMRP activity, may involve proteins for which synaptic translation is regulated by FMRP, or may involve defects in neurotransmitter systems shown to be dysregulated in FXS models. Molecules aimed at targets in pathways that are dysregulated in the absence of FMRP are now being developed and tested in academic laboratories and through the pharmaceutical industry, in order to offer effective drug therapies for affected patients with FXS. It is expected that many of these targeted treatments will have therapeutic overlap in subsets of individuals with ASD.

This conference will bring together leading scientists and clinicians in the Fragile X and ASD fields. Topics will include molecular genetics, model system characterizations, synaptic signaling and function studies, small molecule trials and clinical reports.

+ show speakers and program
2:00 pm - 9:00 pm Arrival and Check-in (Office Closed 6:00 pm - 7:00 pm)
6:00 pm Dinner
7:30 pm - 7:40 pm Welcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pm Keynote Session - Advances in Fragile X and Autism
7:40 pm - 7:50 pm Kevin Moses (Wellcome Trust)
"Introduction to the inaugural fragile X and autism GRC"
7:50 pm - 8:50 pm Mark Bear (Massachusetts Institute of Technology)
"Fulfilling the Promise of Molecular Medicine in Fragile X and Autism"
8:50 pm - 9:30 pm Discussion
MONDAY
7:30 am - 8:30 am Breakfast
9:00 am - 12:30 pm Activity-Dependent Protein Synthesis in Neurons
Discussion Leader: Joel Richter (University of Massachusetts Medical School)
9:00 am - 9:25 am Joel Richter (University of Massachusetts Medical School)
"Rescuing fragile X"
9:25 am - 9:35 am Discussion
9:35 am - 10:00 am Mauro Costa-Mattioli (Baylor College of Medicine)
"Translational regulatory mechanism in long-term mnemonic processes"
10:00 am - 10:10 am Discussion
10:10 am - 10:30 am Group Photo / Coffee Break
10:30 am - 10:55 am Eric Klann (New York University)
"Dysregulated translational control in autism spectrum disorders"
10:55 am - 11:05 am Discussion
11:05 am - 11:30 am Ray Kelleher (Harvard Medical School)
"Impaired Translational Homeostasis in the Autistic Brain"
11:30 am - 11:40 am Discussion
11:40 am - 12:05 pm Emily K. Osterweil (Massachusetts Institute of Technology)
"The role of mGluR5 and ERK1/2-mediated protein synthesis in fragile X syndrome"
12:05 pm - 12:30 pm Discussion
12:30 pm Lunch
1:30 pm - 4:00 pm Free Time
4:00 pm - 6:00 pm Poster Session
6:00 pm Dinner
7:30 pm - 9:30 pm Temporal and Cell-Specific Functions of FMRP
Discussion Leader: Jennifer Darnell (Rockefeller University)
7:30 pm - 7:50 pm Jennifer Darnell (Rockefeller University)
"A cell-specific approach for the identification of mRNA targets of translational repression by FMRP"
7:50 pm - 8:00 pm Discussion
8:00 pm - 8:20 pm Xinyu Zhao (University of Wisconsin-Madison)
"FMRP controls the fate of neural stem cells and governs the process of neurogenesis"
8:20 pm - 8:30 pm Discussion
8:30 pm - 8:50 pm Jay Gibson (University of Texas, Southwestern)
"Change in neocortical connectivity in the Fmr1 KO is due to presynaptic deletion of Fmr1"
8:50 pm - 9:00 pm Discussion
9:00 pm - 9:20 pm Kendal Broadie (Vanderbilt University)
"The Drosophila model of fragile X syndrome"
9:20 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 am Breakfast
9:00 am - 12:30 pm The Presynaptic Compartment
Discussion Leader: Justin Fallon (Brown University)
9:00 am - 9:25 am Michael A Sutton (University of Michigan)
"Dual control of presynaptic and postsynaptic function by dendritic protein synthesis"
9:25 am - 9:35 am Discussion
9:35 am - 10:00 am Deanna L. Benson (Mount Sinai School of Medicine)
"Local synthesis and synapse stabilization"
10:00 am - 10:10 am Discussion
10:10 am - 10:30 am Coffee Break
10:30 am - 10:55 am Craig C. Garner (Stanford University)
"Mechanisms regulating synaptic dysfunction in Phelan McDermid Syndrome"
10:55 am - 11:05 am Discussion
11:05 am - 11:30 am Michael Akins (Brown University)
"Presynaptic Fragile X Proteins"
11:30 am - 11:40 am Discussion
11:40 am - 12:05 pm Sumantra Chattarji (National Centre for Biological Sciences)
"Pharmacological reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome"
12:05 pm - 12:30 pm Discussion
12:30 pm Lunch
1:30 pm - 4:00 pm Free Time
4:00 pm - 6:00 pm Poster Session
6:00 pm Dinner
7:30 pm - 9:30 pm Circuits
Discussion Leader: Peter Kind (University of Edinburgh)
7:30 pm - 7:50 pm John Isaacs (Eli Lilly and Company)
"Mechanisms of circuit dysfunction in the FMRP1 knock out mouse sensory system"
7:50 pm - 8:00 pm Discussion
8:00 pm - 8:20 pm Anis Contractor (Northwestern University)
"Cortical critical periods in the mouse model of Fragile X syndrome"
8:20 pm - 8:30 pm Discussion
8:30 pm - 8:50 pm Karl Deisseroth (Stanford University)
"Optogenetics and Social Behavior"
8:50 pm - 9:00 pm Discussion
9:00 pm - 9:20 pm Rhiannon Meredith (VU University)
"Early development of synaptic networks in Fmr1-KO"
9:20 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 am Breakfast
9:00 am - 12:30 pm The Molecular Basis of Autism, FXS and Developmental Cognitive Disorders I
Discussion Leader: Seth G.N. Grant (University of Edinburgh)
9:00 am - 9:25 am Seth G.N. Grant (University of Edinburgh)
"Genetic dissection of postsynaptic mechanisms of cognition in humans and mice"
9:25 am - 9:35 am Discussion
9:35 am - 10:00 am Catalina Betancur (Université Pierre et Marie Curie)
"Etiological heterogeneity in autism spectrum disorders: unraveling the mystery one gene at a time"
10:00 am - 10:10 am Discussion
10:10 am - 10:30 am Coffee Break
10:30 am - 10:55 am Thomas Sudhof (Stanford University)
"Neurexins and Neuroligins - From Synaptic Cell Adhesion to Autism"
10:55 am - 11:05 am Discussion
11:05 am - 11:30 am Luis Parada (UT Southwestern Medical Center)
"Analysis of FMR-1 deletion in a subpopulation of post-mitotic neurons in mouse cortex and hippocampus"
11:30 am - 11:40 am Discussion
11:40 am - 12:05 pm Claudia Bagni (University of Rome "Tor Vergata", Catholic University of Leuven)
"Local protein synthesis shapes and reshapes the synapses: linking fragile X and autism"
12:05 pm - 12:30 pm Discussion
12:30 pm Lunch
1:30 pm - 4:00 pm Free Time
4:00 pm - 6:00 pm Poster Session
6:00 pm Dinner
7:00 pm - 7:30 pm Business Meeting
Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair
7:30 pm - 9:30 pm The Molecular Basis of Autism, FXS and Developmental Cognitive Disorders II
Discussion Leader: Kimberly Huber (UT Southwestern Medical Center)
7:30 pm - 7:50 pm Kimberly Huber (UT Southwestern Medical Center)
"Mechanisms of synapse elimination by autism-linked genes"
7:50 pm - 8:00 pm Discussion
8:00 pm - 8:20 pm Gary Bassell (Emory University School of Medicine)
"FMRP mediated control of translation and signaling"
8:20 pm - 8:30 pm Discussion
8:30 pm - 8:50 pm Leonard K. Kaczmerak (Yale University School of Medicine)
"Regulation of potassium channels by FMRP"
8:50 pm - 9:00 pm Discussion
9:00 pm - 9:20 pm Lu Chen (Stanford University)
"Synaptic Retinoic Acid Signaling in the FXS mouse model"
9:20 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 am Breakfast
9:00 am - 12:30 pm Outcome Measures in Fly, Mouse and Man
Discussion Leader: Len Abbeduto (MIND Institute, University of California, Davis)
9:00 am - 9:25 am Thomas Jongens (University of Pennsylvania)
"Targeting the Insulin Pathway in the Drosophila Model of Fragile X"
9:25 am - 9:35 am Discussion
9:35 am - 10:00 am Richard E. Paylor (Baylor College of Medicine)
"Fmr1 KO rats: a new model for fragile X syndrome"
10:00 am - 10:10 am Discussion
10:00 am - 10:30 am Coffee Break
10:30 am - 10:55 am Allen Reiss (Stanford University School of Medicine)
"Elucidating imaging biomarkers for treatment and prevention studies of fragile X syndrome"
10:55 am - 11:05 am Discussion
11:05 am - 11:30 am David Hessl (MIND Institute, University of California, Davis)
"Proving efficacy in FXS clinical trials: measure options, present and future"
11:30 am - 11:40 am Discussion
11:40 am - 12:05 pm Len Abbeduto (MIND Institute, University of California, Davis)
"Expressive Language Sampling as an Outcome Measure for Clinical Trials in Fragile X Syndrome"
12:05 pm - 12:30 pm Discussion
12:30 pm Lunch
1:30 pm - 4:00 pm Free Time
4:00 pm - 6:00 pm Poster Session
6:00 pm Dinner
7:30 pm - 9:30 pm Clinical Trials of Targeted Treatments
Discussion Leader: Paul Wang (Seaside Therapeutics)
7:30 pm - 7:50 pm Paul Wang (Seaside Therapeutics)
"Neurobehavioral biomarkers and disease-modifying endpoints in clinical trials"
7:50 pm - 8:00 pm Discussion
8:00 pm - 8:20 pm Mustafa Sahin (Children's Hospital Boston, Harvard Medical School)
"Mechanisms of neurocognitive dysfunction and treatment trials in tuberous sclerosis complex"
8:20 pm - 8:30 pm Discussion
8:30 pm - 8:50 pm Randi Hagerman (MIND Institute, University of California, Davis)
"Minocycline treatment for fragile X syndrome"
8:50 pm - 9:00 pm Discussion
9:00 pm - 9:20 pm George Apostal (Novartis)
"Results with the fragile X-specific Aberrant Behavior Checklist in a pharmacotherapeutic study with AFQ056/mavoglurant"

10 Jun - 15 Jun 2012
Easton
United States of America
meeting website