Developing New Treatments for Tourette Syndrome: Clinical and Basic Science Dialogue

Developing New Treatments for Tourette Syndrome: Clinical and Basic Science Dialogue
September 10-12, 2006
Washington, D.C.

The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health (NIMH), the NIH Office of Rare Diseases (ORD), and the Tourette Syndrome Association (TSA) jointly sponsored a workshop to develop new and improved treatments for children and adults afflicted with Tourette syndrome (TS). The workshop was held on September 10-12, 2006, and included approximately 100 scientists, clinicians, and industry representatives in the fields of basic neurobiology, behavioral sciences, neurogenetics, neuroimaging, neurological disorders, motor disorders, and child psychiatry. The attendees from within and outside the TS field convened with the express purpose of bridging the communication and information gap between basic and clinical science disciplines to evaluate the biological and clinical basis for existing TS treatments and to understand recent updates in the neurobiology of TS in order to define new therapeutic directions.

The meeting began with an overview of the phenomenology of TS and existing treatments. TS is characterized by an enduring pattern of motor and phonic tics that present during childhood. According to current best estimates, TS affects approximately 6 of every 1000 schoolchildren. The severity and frequency of tics peak early during the second decade of life, but then decline considerably in many patients by their late teens and early 20s. Currently, there is no curative pharmacological treatment for TS, but several agents have proven successful at attenuating tics and improving psychosocial functioning. Since TS is associated with improper dopaminergic tone in the brain, atypical neuroleptics (e.g., risperidone) and typical neuroleptics (e.g., haloperidol) that function by blocking dopamine signaling at D2 receptors are commonly prescribed. Other commonly used agents include 2-adrenergic agonists (e.g., clonidine). Botulinum toxin A is increasingly being used to treat severe focal tics. In terms of behavioral approaches for tic control, habit reversal training, which employs competing responses to block tic manifestation, has been shown to be an effective technique in adults and appears to also work in children. A handful of case studies suggest that deep brain stimulation, in which electrodes are implanted into specific brain regions to deliver electrical pulses to prevent tics, is a promising approach for controlling TS, but considerably more study of the technique is needed.

The next portion of the workshop centered around presentations highlighting the brain structures and neural circuitry implicated in TS. Research indicates that TS is very likely caused by abnormal signaling between various circuits in the brain that manifests during development. The chief circuit involves the cerebral cortex, basal ganglia, and thalamocortical regions, with the basal ganglia being a key node in the circuit. Dopamine signaling within the basal ganglia serves to define the salience of information by filtering out "inappropriate" behaviors. Like others, individuals with TS are constantly bombarded with stimuli at the site of the basal ganglia; however, this region of the brain is impaired in its ability to discriminate between salient and nonsalient signals. Importantly, it appears that the ventral striatum is the primary locus of dysfunction within the basal ganglia in TS individuals. Although the cause of basal ganglia dysfunction is not well understood, clues may be found by examining the structure of TS brains. A comparison of postmortem basal ganglia tissue from patients with severe TS and normal controls indicates a below-normal density of inhibitory neurons in the striatum and an above-normal density in the internal segment of the globus pallidus within the basal ganglia.

Additional information about the pathology of TS may be gleaned from studies of related neural processes and/or abnormalities. Striatal neurons and dopamine signaling play a key role in the process of habit formation, particularly habits involving complex and socially relevant behavioral sequences, as is observed in TS patients. Certain areas of neural convergence in the striatum may be particularly sensitive to dopamine modulation during decision-making and habit formation - areas that may be hypersensitive or overactive in TS. Related to habit formation is the biology of addiction, which may parallel the neurobiochemical processes occurring in TS. Individuals with strong tics may have progressed through the process of overlearning such that they become "addicted" to tic behavior as a means to relieve the mounting internal stress or body tension that is often described as characteristic of TS. Addiction studies have revealed that overlearning is associated with heavy dopamine release that activates the prefrontal cortex, which, in turn, releases a surge of glutamate on the nucleus accumbens that then drives drug seeking.

There are no animal models for TS, but syntactic chain grooming in rats is a relevant behavior to study since it is sequential, rule driven, and predictable, yet flexible, much like tics. In addition, studies have shown that the stereotypical movement is regulated by the ventral striatum. Interestingly, D1 agonists dramatically upregulate chain behavior, suggesting that D1 receptor antagonists may suppress this behavior. Because tics are often preceded by premonitory urges, additional insight into the neurobiology of TS and potential therapeutics may be gained by studying prepulse inhibition in rats, which is abrogated by increased dopamine signaling and/or disruption of the ventral striatum.

Pharmacological therapies for TS have traditionally focused on dopamine mechanisms. However, just as different areas of the brain are implicated in TS, so too are different neurotransmitter systems that interact and overlap to contribute to the pathophysiology of TS. Salient interactions include those between dopamine and glutamate, dopamine and serotonin, and dopamine and GABA.

Given the neurobiology underlying TS pathogenesis and the similarities between TS and other neural processes, several attractive pharmacotherapeutic targets for TS emerged during the workshop. These include compounds targeting monoaminergic systems (e.g., D1 receptor antagonists, serotonin agonists or selective serotonin reuptake inhibitors), agents that regulate the prefrontal glutamatergic drive to the nucleus accumbens (e.g., N-acetylcysteine, modafinil), and agents that reinstate GABA receptor function or enhance GABA activity. The application of brain imaging, particularly between sibling pairs, and better identification of the genes involved in TS (e.g., SLITRK1) will facilitate more refined therapeutic approaches.

In order to better poise the TS field to make substantial progress in translating research from the bench to the bedside, several individuals investigating other human disorders presented their experiences with coordinating and accelerating the therapy development process. One particular strategy that may bring TS therapeutics to the clinic relatively quickly and easily is to identify new applications for approved drugs or drugs that went through clinical trials but failed to receive FDA approval. Additionally, the NIH offers several resources to facilitate translational research.

In the concluding discussions, the workshop participants recognized that TS drug development is hampered by two difficulties: (1) there is no animal model of TS for preclinical analysis, and (2) it is difficult to enroll large clinical trials to assess a particular therapeutic. To circumvent these difficulties, it was proposed that a collaborative pilot study group be formed to perform small experimental trials in TS patients in order to cultivate larger trials of appropriate drugs in appropriate patients. The formation of a pilot study consortium would serve to augment the TSA International Genetics Consortium, the TSA Behavioral Sciences Consortium, and the TSA Neuroimaging Consortium already in existence. Participants also expressed that larger clinical trials must be thoughtfully designed to enable researchers to discern which subgroups of TS patients (e.g., based on genetic polymorphisms, functional imaging, the type and severity of tics) derive benefit from a given therapeutic. In addition, some proposed that other measures of improvement, aside from tics, be included in such analyses, such as improvements in quality of life. These ideas have the opportunity to gain further momentum since the TSA is planning another meeting in early 2007 that will focus on pragmatic approaches to clinical trial design and treatment exploration.

Developing New Treatments for Tourette Syndrome: Clinical and Basic Science Dialogue
September 10-12, 2006
Watergate Hotel, Washington DC
Agenda

Sponsored by the:

National Institutes of Health (NIH): National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), Office of Rare Diseases (ORD)
Tourette Syndrome Association (TSA)

Conference Organizers: Laura Mamounas, Ph.D. (NINDS), Ann Wagner, Ph.D. (NIMH), Giovanna Spinella, M.D. (ORD), Sue Levi-Pearl (TSA)

Science Planning Committee: Chair: Lawrence Scahill, Ph.D., M.S.N.(Yale University); Jonathan Mink, M.D., Ph.D. (University of Rochester), Neal Swerdlow, M.D., Ph.D. (University of California, San Diego), John Walkup, M.D. (Johns Hopkins University School of Medicine), Jorge Juncos, M.D. (Emory University School of Medicine), Peter Hollenbeck, Ph.D. (Purdue University), Harvey Singer, M.D. (Johns Hopkins University School of Medicine), Ann Graybiel, Ph.D. (Massachusetts Institute of Technology), Amy Arnsten, Ph.D. (Yale University), and Eric Nestler, M.D., Ph.D. (University of Texas Southwestern Medical Center)

Background and Goals of Workshop:

Tourette Syndrome (TS) is a familial, neurological disorder defined by the childhood onset of chronic motor and vocal tics. The tics of TS most often involve rapid, jerky movements such as blinking, facial movements, head jerking and simple vocalizations such as throat clearing, coughing, grunting and other brief noises. In other cases, however, the tics are more complex involving multiple muscle groups and more complex vocalizations including cursing and repetition of words or phrases. In addition to tics, a high percentage of patients with TS have significant problems with obsessive-compulsive behaviors (OCD) as well as inattention, hyperactivity, and impulsiveness (ADHD) or a combination of these problems. In many cases, these co-occurring conditions when present are more impairing than the tics themselves. Although TS and associated conditions are not life-threatening, the tics can be debilitating, painful and may cause impairment at school or work and social isolation, especially in children. Given the current estimates of prevalence ranging from 0.1 to 1% for TS (up to 6% for transient tics), TS is a significant public health problem.

Most pharmacological treatment trials in TS have focused on tic reduction. Antipsychotic drugs with potent dopamine blockade at D2 receptors are the best-studied and most commonly prescribed class of medications used for tic reduction. Although available evidence indicates that the D2 antagonists are effective for reducing tics, at least in the short-term, these agents are not free of adverse effects, and are often discontinued because of debilitating or dangerous side effects (sedation, dyskinesias, weight gain, cardiac arrhythmias in some people). Another commonly used class of medications is the alpha-2-norepinephrine agonist class. However, the magnitude of effect is typically moderate with this class of drugs, and success with alternative medications has been limited. Preliminary data are available for dopamine agonists and drugs that enhance GABA. However, few drug treatments have been selected in accordance with contemporary understanding of putative TS pathophysiology. Recently, converging information from neuroimaging, neuropathology, psychophysiology, genetics and behavioral neuroscience offer exciting new opportunities for understanding the etiology of TS and for developing optimal treatments for this disorder. In addition to pharmacological therapies, new behavioral approaches suggest novel opportunities for reducing tics and associated disability in people with TS through non-pharmacological means as well as with combined treatments. We hope that a focused dialogue between basic neuroscientists and clinical investigators will guide the identification and selection of candidate treatments for TS in the near term and lead to improved strategies for therapy development in the future.

The overall goal of this conference is to develop improved treatments for children and adults with Tourette syndrome. The conference will bring together clinical investigators, basic and translational scientists representing a range of scientific disciplines from within outside the TS field to evaluate the evidence for existing TS treatments and the latest information on the neurobiology that is relevant to TS in order to identify new treatments. Another goal is to adopt novel strategies for therapy development in TS based on insights gained from translational approaches in other disease areas and from industry. The workshop will conclude with a session on defining future directions in neuroscience and clinical research. The conference hopes to encourage new interdisciplinary collaborations among junior and established investigators in order to guide the identification, development and testing of new treatments for people with TS.

The conference organizers plan to disseminate the discussions and recommendations from this meeting to investigators and clinicians working in the TS field. The published proceedings will aim to identify opportunities and new directions in translational and clinical research in TS.

Developing New Treatments for Tourette Syndrome: Clinical and Basic Science Dialogue
September 10-12, 2006
Watergate Hotel, Washington DC

AGENDA

Sunday	September 10, 2006
4:30 to 7:00 PM	Registration, Welcome Reception and Dinner
Introductory Presentations & Overview: Phenomenology of Tourette Syndrome (TS) and Existing Treatments
7:00 to 7:05 PM	Welcome and introductions - Ann Wagner, Ph.D. (National Institute of Mental Health; NIMH)
7:05 to 7:15 PM	Opening remarks - Story Landis, Ph.D. (Director, National Institute of Neurological Disorders and Stroke; NINDS) and Thomas Insel, M.D. (Director, NIMH)
7:15 to 7:30 PM	Charge of conference: translational goal - Laura Mamounas, Ph.D. (NINDS), John Walkup, M.D. (Johns Hopkins University School of Medicine), Jonathan Mink, M.D., Ph.D. (University of Rochester)
7:30 to 7:55 PM	Tourette Syndrome phenomenology: natural history, clinical features, and potential age effects - Larry Scahill, Ph.D., M.S.N. (Yale University)
7:55 to 8:20 PM	Classes of drugs used in the treatment of TS: mechanism of action, magnitude of response, and current gaps in treatment - Leon Dure, M.D. (University of Alabama at Birmingham)
8:20 to 8:45 PM	Habit Reversal Behavioral Therapy - John Piacentini, Ph.D. (University of California, Los Angeles)
8:45 to 9:10 PM	Surgical treatments: Deep Brain Stimulation - Jonathan Mink, M.D., Ph.D. (University of Rochester)
9:10 to 9:30 PM	Discussion
Monday	September 11, 2006
Basal Ganglia and Tourette Syndrome (Chair: Jonathan Mink, M.D., Ph.D.)
8:30 to 8:35 AM	Overview and goals of the session - Jonathan Mink, M.D., Ph.D. (University of Rochester)
8:35 to 8:50 AM	Why is TS thought to be a basal ganglia disorder? - Roger Albin, M.D. (University of Michigan)
8:50 to 9:05 AM	Basal Ganglia 'Loops' with the Cerebral Cortex: Motor, Cognitive and Affective Circuits - Peter Strick, Ph.D. (University of Pittsburgh)
9:05 to 9:20 AM	Striatal, nigral and dopamine mechanisms of sequential motor actions - J. Wayne Aldridge, Ph.D. (University of Michigan)
9:20 to 9:35 AM	Abnormalities of basal ganglia interneurons in TS brains - Flora Vaccarino, M.D. (Yale University School of Medicine)
9:35 to 10:15 AM	Discussion: panel includes Chair/speakers and Ann Graybiel, Ph.D. (Massachusetts Institute of Technology), Mahlon DeLong, M.D. (Emory University School of Medicine), Suzanne Haber, Ph.D. (University of Rochester School of Medicine)
10:15 to 10:45 AM	Break
Sensorimotor Circuitry and Learning: Relevance to TS and Therapy Development (Chair: Suzanne Haber, Ph.D.)
10:45 to 10:50 AM	Overview and goals of session - Suzanne Haber, Ph.D. (University of Rochester School of Medicine)
10:50 to 11:05 AM	Neural circuit regulation of sensorimotor gating in TS - Neal Swerdlow, M.D., Ph.D. (University of California, San Diego)
11:05 to 11:20 AM	The basal ganglia - sensory structures in disguise? - Krish Sathian, M.D., Ph.D. (Emory University School of Medicine)
11:20 to 11:35 AM	Neurobiology of reward and its relevance to the learning and unlearning of repetitive motor sequences - Peter Kalivas, Ph.D. (Medical University of South Carolina)
11:35 to 11:50 AM	The neural basis of habit learning and its relevance to TS - Ann Graybiel, Ph.D. (Massachusetts Institute of Technology)
11:50 AM to 12:30 PM	Discussion: panel includes Chair/speakers and Jorge Juncos, M.D. (Emory University School of Medicine)
12:30-1:30 PM	Lunch
Neurotransmitter Interactions in TS: Implications for Treatment Target Selection (Chair: D. James Surmeier, Ph.D.)
1:30 to 1:40 PM	Overview and goals of session - D. James Surmeier, Ph.D. (Northwestern University)
1:40 to 1:55 PM	Dopamine-glutamate interactions - D. James Surmeier, Ph.D. (Northwestern University)
1:55 to 2:10 PM	Dopamine-serotonin interactions - Anthony Grace, Ph.D. (University of Pittsburgh)
2:10 to 2:25 PM	GABA-dopamine interactions - Celeste Napier, Ph.D. (Loyola University Chicago)
2:25 to 2:40 PM	Possible pharmacological targets for neuropeptides - Becky Kinkead, Ph.D. (Emory University School of Medicine)
2:40 to 3:15 PM	Discussion: panel includes Chair/speakers and Harvey Singer, M.D. (Johns Hopkins University School of Medicine)
3:15 to 3:45 PM	Break
Emerging Directions in TS Research: Translational Implications (Chair: F. Xavier Castellanos, M.D.)
3:45 to 4:00 PM	Overview of session. Moving from the inside out: new approaches in the study of TS - F. Xavier Castellanos, M.D. (New York University School of Medicine)
4:00 to 4:25 PM	Role of imaging in uncovering the neurobiology of TS - Kirk Frey, M.D., Ph.D. (University of Michigan)
4:25 to 4:50 PM	Site selection for DBS: implications for the pathophysiology and treatment of TS - Mahlon DeLong, M.D. (Emory University School of Medicine)
4:50 to 5:15 PM	SLITRK1 finding: implications for translational research in TS - Matthew State, M.D., Ph.D. (Yale University School of Medicine)
5:15 to 5:30 PM	Intracellular Blockade of Stimulant-induced Stereotypies - Paul Lombroso, M.D. (Yale University School of Medicine)
5:30 to 6:00 PM	Discussion: panel includes Chair/speakers and Nenad Sestan, M.D., Ph.D. (Yale University School of Medicine)
Tuesday	September 12, 2006
Coordinating and Accelerating the Therapy Development Process: Lessons from other Disorders (Co-chairs: Laura Mamounas, Ph.D. and Ann Wagner, Ph.D.)
8:00 to 8:25 AM	Structuring a drug development project: lessons from Spinal Muscular Atrophy - Jill Heemskerk, Ph.D. (NINDS)
8:25 to 8:50 AM	Challenges of establishing a drug discovery program in an academic setting: how do you know when it's time to translate? - Ann Young, M.D., Ph.D. (Harvard Medical School)
8:50 to 9:15 AM	Lessons from Huntington's Disease: private-sector strategies for therapy development - Celia Dominguez, Ph.D. (CHDI, Inc.)
9:15 to 9:35 AM	NIH and NIMH resources for facilitating translational research - Linda Brady, Ph.D. (NIMH)
9:35 to 9:50 AM	NINDS resources for translational research - Tom Miller, Ph.D. (NINDS)
9:50 to 10:30 AM	Discussion: Focus on assay and animal model development for TS (Discussion Leader: Neil Swerdlow, M.D., Ph.D. University of California, San Diego)
10:30 to 11:00AM	Break
Compound Selection: Paths Worth Pursuing (Chair: Harvey Singer, M.D.)
11:00 to 11:05 AM	Overview and goals of session - Harvey Singer, M.D. (Johns Hopkins University School of Medicine)
11:05 to 11:25 AM	Compounds targeting monoaminergic systems (DA, 5-HT, NE) in the treatment of TS - Don Gilbert, M.D., M.S. (Cincinnati Children's Hospital Medical Center) and Anthony Grace, Ph.D. (University of Pittsburgh)
11:25 to 11:45 AM	GABAergic drugs in the treatment of TS - Roger Kurlan, M.D. (University of Rochester) and Robert Macdonald, M.D., Ph.D. (Vanderbilt University)
11:45 AM to 12:05 PM	Glutamatergic compounds for TS - Joseph Coyle, M.D. (Harvard Medical School) and Harvey Singer, M.D. (Johns Hopkins University School of Medicine)
12:05 to 1:00 PM	Discussion: panel includes Chair/speakers and Debra Babcock, Ph.D., M.D. (NINDS), James McCracken, M.D. (University of California, Los Angeles), D. James Surmeier, Ph.D. (Northwestern University), T. Celeste Napier, Ph.D. (Loyola University Chicago), Becky Kinkead, Ph.D. (Emory University School of Medicine)
Working Lunch & Brain Storming Session: Given the information that has been shared, where do we go from here?
1:00 to 2:30 PM	Discussion leaders: John Walkup, M.D. (Johns Hopkins University School of Medicine, Jorge Juncos, M.D. (Emory University School of Medicine), Larry Scahill, Ph.D., M.S.N. (Yale University)

Participant List

Roger Albin, M.D.
Professor
Department of Neurology
University of Michigan

J. Wayne Aldridge, Ph.D.
Research Associate Professor
Department of Neurology
University of Michigan

Debra J. Babcock, Ph.D., M.D.
Program Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Kevin J. Black, M.D.
Associate Professor
Departments of Psychiatry, Neurology, Radiology, and Neurobiology
School of Medicine
Washington University

Linda S. Brady, Ph.D.
Director
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
National Institutes of Health

Kyle T. Brown
Founder and Chief Executive Officer
Innolyst, Inc.

Cathy L. Budman, M.D.
Director
Movement Disorders Program in Psychiatry
New York University School of Medicine
North Shore Health Systems

F. Xavier Castellanos, M.D.
Director
Institute of Pediatric Neuroscience
Department of Psychiatry
Child Study Center
New York University School of Medicine

Daofen Chen, Ph.D.
Program Director
Systems and Cognitive Neuroscience
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Kathleen Clarence-Smith, M.D., Ph.D.
Chief Executive Officer
Prestwick Pharmaceuticals

Monica Coenraads, M.B.A.
Director of Research
Rett Syndrome Research Foundation

Barbara J. Coffey, M.D., M.S.
Director
Institute for Tourettes and Movement Disorders
Associate Professor, Child Study Center
New York University School of Medicine

Keith A. Coffman, M.D.
Fellow
Pediatric Scientist Development Program
Division of Pediatric Neurology
Department of Pediatrics
University of Pittsburgh
Children's Hospital of Pittsburgh

Heather M. Cowley, Ph.D.
Manager
Medical and Scientific Programs
Tourette Syndrome Association

Joseph T. Coyle, M.D.
Eben S. Draper Professor
Department of Psychiatry and Neuroscience
Harvard Medical School

Mahlon R. Delong, M.D.
Professor and Director of Neuroscience
Department of Neurology
Emory University School of Medicine

Martha B. Denckla, M.D.
Director
Developmental Cognitive Neurology
Professor of Neurology, Kennedy Krieger Institute
Professor of Neurology, Pediatrics, and Psychiatry
Johns Hopkins University School of Medicine

Marian DiFiglia, Ph.D.
Professor
Department of Neurology
Massachusetts General Hospital
Harvard Medical School

Celia Dominguez, Ph.D.
Vice President
Department of Chemistry
CHDI, Inc.

Leon S. Dure, M.D.
Professor
Department of Pediatrics and Neurology
University of Alabama at Birmingham

Shlomit Ritz Finkelstein, Ph.D.
Graduate Student
Institute of the Liberal Arts
Emory University

Nelson B. Freimer, M.D.
Professor and Director
Center for Neurobehavioral Genetics
University of California, Los Angeles

Kirk A. Frey, M.D., Ph.D.
Professor
Department of Radiology and Neurology
University of Michigan

Donald L. Gilbert, M.D., M.S.
Associate Professor
Department of Pediatrics and Neurology
Cincinnati Children's Hospital Medical Center

Anthony A. Grace, Ph.D.
Professor of Neuroscience, Psychiatry, and Psychology
Department of Neuroscience
University of Pittsburgh

Ann M. Graybiel, Ph.D.
Walter A. Rosenblith Professor of Neuroscience
Department of Brain and Cognitive Sciences Investigator
McGovern Institute for Brain Research
Massachusetts Institute of Technology

Dorothy E. Grice, M.D.
Division Director
Child and Adolescent Psychiatry
Department of Psychiatry
New Jersey Medical School
University of Medicine and Dentistry of New Jersey

Katrina Gwinn-Hardy, M.D.
Program Director
Neurogenetics
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Suzanne N. Haber, Ph.D.
Professor
Department of Pharmacology and Physiology
University of Rochester School of Medicine

Jill Heemskerk, Ph.D.
Program Director
Department of Technology Development
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Deborah Hirtz, M.D.
Program Director
Clinical Trials
National Institute of Neurological Disorders and Stroke
National Institutes of Health

David E. Housman, Ph.D.
Ludwig Professor of Biology
Center for Cancer Research
Massachusetts Institute of Technology

Thomas R. Insel, M.D.
Director
National Institute of Mental Health
National Institutes of Health

Samay Jain, M.D.
Assistant Professor of Neurology
Clinical Director of Movement Disorders Division
University of Pittsburgh Medical Center

Scott Janis, Ph.D.
Clinical Research Project Manager
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Joseph Jankovic, M.D.
Professor of Neurology
Department of Neurology
Director, Parkinson's Disease Center and Movement Disorders Clinic
Baylor College of Medicine

Mary E. Jenkins, M.D., F.R.C.P.C.
Assistant Professor
Department of Neurology
London Health Sciences Centre
Canada

Jorge L. Juncos, M.D.
Associate Professor of Neurology
Movement Disorders
Department of Neurology
Emory University School of Medicine

Peter W. Kalivas, Ph.D.
Professor and Chair
Department of Neurosciences
Medical University of South Carolina

Robert A. King, M.D.
Professor
Department of Child Psychiatry
Child Study Center
Yale University School of Medicine

Becky L. Kinkead, Ph.D.
Assistant Professor
Department of Psychiatry and Behavioral Sciences
Emory University School of Medicine

Roger M. Kurlan, M.D.
Professor
Department of Neurology
University of Rochester

Story C. Landis, Ph.D.
Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Frank Leonard
Senior Director
Commercial Operations
Prestwick Pharmaceuticals

Sue Levi-Pearl
Vice President
Medical and Scientific Programs
Tourette Syndrome Association

Paul Lombroso, M.D.
Professor
Child Study Center
Yale University School of Medicine

Ernie Lyons, Ph.D.
Scientific Review Administrator
Scientific Review Branch
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Robert Macdonald, M.D., Ph.D.
Professor and Chairman
Department of Neurology
Vanderbilt University

Laura A. Mamounas, Ph.D.
Program Director
Neurogenetics and Development
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Carol Mathews, M.D.
Associate Professor
Program for the Genetics and Epidemiology of Neuropsychiatric Symptoms
Department of Psychiatry
University of California, San Francisco

John M. McCall, Ph.D.
Senior Consultant
PharMac LLC

James T. McCracken, M.D.
Professor
Child and Adolescent Division of Psychiatry
Semel Institute for Neuroscience and Human Behavior
University of California, Los Angeles

William M. McMahon, M.D.
Professor
Department of Psychiatry
University of Utah

Thomas Miller, Ph.D.
Program Director
Department of Technology Development
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Jonathan W. Mink, M.D., Ph.D.
Associate Professor
Child Neurology Program
Department of Neurology
University of Rochester

Michelle M. Morrow, Ph.D.
Postdoctoral Researcher
Department of Neurobiology
University of Pittsburgh

Tanya K. Murphy, M.D.
Associate Professor and Chief
Division of Child and Adolescent Psychiatry
Department of Psychiatry
University of Florida

T. Celeste Napier, Ph.D.
Professor
Department of Pharmacology
Stitch School of Medicine
Loyola University Chicago

Kara A. Nyberg, Ph.D.
Science/Medical Writer

Joseph J. Pancrazio, Ph.D.
Program Director
Division of Extramural Research, Repair and Plasticity Cluster
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Gahan Pandina, Ph.D.
Director
Clinical Management
Janssen Medical Affairs
Janssen, LP

David Pauls, Ph.D.
Professor
Psychiatric and Neurodevelopmental Genetics Unit
Center of Human Genetic Research
Massachusetts General Hospital
Harvard Medical School

Alan L. Peterson, Ph.D.
Professor
Behavioral Medicine
Department of Psychiatry
University of Texas Health Science Center at San Antonio

John C. Piacentini, Ph.D.
Professor in Residence
Child and Adolescent Psychiatry
University of California, Los Angeles

Carlos R. Plata-Salaman, D.Sc., M.D.
Head
Global External Research and Development
Eli Lilly and Company

Eldrige D. Proctor, M.P.A.
Legislative Associate
Government Relations
Tourette Syndrome Association

Jean-Baptiste Riviere, M.Sc.
CHUM Research Center
Université de Montréal

Floyd R. Sallee, Ph.D., M.D.
Professor
Department of Psychiatry
University of Cincinnati School of Medicine

Krish Sathian, M.D., Ph.D.
Professor
Department of Neurology
Emory University School of Medicine

Lawrence D. Scahill, Ph.D., M.S.N.
Professor
Child Study Center
Yale University

Mark Scheideler, Ph.D.
Program Director, Molecular Libraries
Technology Development
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Nenad Sestan, M.D., Ph.D.
Assistant Professor
Department of Neurobiology
Yale University School of Medicine

David Silbersweig, M.D.
Director
Functional Neuroimaging Laboratory
Department of Psychiatry
Weill Medical College of Cornell University

Harvey S. Singer, M.D.
Haller Professor of Pediatric Neurology
Department of Neurology
Johns Hopkins University School of Medicine

Giovanna M. Spinella, M.D.
Science and Program Consultant
Office of Rare Diseases
National Institutes of Health

David Stamler, M.D.
Chief Scientific Officer and Head
Department of Research and Development
Prestwick Pharmaceuticals, Inc.

Matthew W. State, M.D., Ph.D.
Harris Associate Professor
Department of Genetics
Child Study Center
Yale University School of Medicine

Peter L. Strick, Ph.D.
Professor
Department of Neurobiology
Co-Director, Center for Neural Basis of Cognition
University of Pittsburgh

Denis G. Sukhodolsky, Ph.D.
Associate Research Scientist
Child Study Center
Yale University School of Medicine

D. James Surmeier, Ph.D.
Professor and Chair
Department of Physiology
Feinberg School of Medicine
Northwestern University

Susan E. Swedo, M.D.
Associate Director for Pediatric Research
Chief, Pediatrics and Developmental Neuropsychiatry Branch
National Institute of Mental Health

Neal R. Swerdlow, M.D., Ph.D.
Professor
Department of Psychiatry
School of Medicine
University of California, San Diego

Judit Ungar, M.S.W.
President
Tourette Syndrome Association

Flora M. Vaccarino, M.D.
Associate Professor
Department of Neurobiology
Child Study Center
Yale University School of Medicine

Robin M. Voigt
Ph.D. Candidate
Department of Pharmacology and Experimental Therapeutics
Loyola University Chicago

Ann E. Wagner, Ph.D.
Chief
Neurodevelopmental Disorders Branch
Division of Pediatric Translational Research and Treatment
National Institute of Mental Health
National Institutes of Health

John T. Walkup, M.D.
Associate Professor
Division of Child and Adolescent Psychiatry
Department of Psychiatry
Johns Hopkins University School of Medicine

Judith R. Walters, Ph.D.
Section Chief
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Lucinda K. Wilson
Senior Project Director
Clinical Division
Prestwick Pharmaceuticals, Inc.

Dean F. Wong, M.D., Ph.D.
Professor
Department of Nuclear Medicine/Radiology
Johns Hopkins University School of Medicine

Douglas W. Woods, Ph.D.
Associate Professor
Department of Psychology
University of Wisconsin-Milwaukee

Anne B. Young, M.D., Ph.D.
Chief
Neurology Service
Department of Neurology
Massachusetts General Hospital
Harvard Medical School

Samuel H. Zinner, M.D.
Assistant Professor
Division of Genetics and Developmental Medicine/Pediatrics
Center on Human Development and Disability
University of Washington