PHRF Mission Statement The mission of the Pitt Hopkins Research Foundation (PHRF) is to support research dedicated to finding a treatment, and an eventual cure of Pitt Hopkins syndrome and other similar disorders. The PHRF is also dedicated to supporting the Pitt Hopkins community with resource recommendations, parental support and the latest medical information.
The Board of Directors of the Pitt Hopkins Research Foundation is comprised of individuals
dedicated to advancing research and supporting families of children and adults with Pitt Hopkins Syndrome. The Board is actively engaged in fundraising efforts towards research, in providing parental support to families worldwide, and in offering communication and media representation for the Foundation.
Officers & Executive Committee
Board Members
Audrey Davidow Lapidus, President
Audrey Davidow Lapidus
Heather Maginn, Secretary
Theresa Pauca
Jessica Fletcher, Director of
Heather Maginn
Theresa Pauca, Vice President Diane Sellew, Treasurer Communications
Eric Lapidus, Director of Fundraising
Eric Lapidus Paul Pauca
Jack Maginn
Jeff Davidow Diane Sellew
Jessica Fletcher Diane Krell
Traci Green
Claudette Marigliani
3rd Annual Pitt Hopkins Research Foundation Symposium & Family Conference
University of Texas Southwestern Dallas, TX November 3rd ,4th & 5th
Items of note_____________________________________________ On Thursday See Jessica Fletcher for more details 12:00 – 4:00 p.m. 2:00 – 4:00 p.m.
Pitt Hopkin Children Blood Draws for Coriell
Embassy Suites, Love Field, Bachman Room
Pitt Hopkins Children Buccal Swabs for Frye lab Embassy Suites, Love Field, Bachman Room
Thursday, November 3 rd, 2016
_____
__
Conference site:
University of Texas Southwestern Medical Center
8:30 - 9:15 a.m
Breakfast at conference site (above)
9:00 – 9:05 a.m.
Welcome Audrey Davidow Lapidus President, Pitt Hopkins Research Foundation Board of Directors
9:05 – 9:15 a.m.
Opening Remarks Craig Powell, MD, PhD, FAAN, FANA Departments of Neurology & Neurotherapeutics, Psychiatry University of Texas Southwestern Medical Center
Pickens Biomedical Building, 14th floor, Private Dining Room, 6001 Forest Park Rd, Dallas, TX 75235
SESSION I
___________________
_____
9:15 – 9:40 a.m.
The Case for HDAC Inhibition Andrew Kennedy, PhD Assistant Professor Bates College
9:40 – 10:05 a.m.
Convergent evidence for hippocampal NMDA receptor hyperfunction in PTHS Ben Philpot, PhD Professor Associate Director, UNC Neuroscience Center Department of Cell Biology & Physiology
10:05 – 10:30 a.m.
Large-scale untargeted metabolomics profiling in Pitt-Hopkins syndrome uncovers phenotypic-associated amino acid and lipid abnormalities Joseph Alaimo, PhD Baylor College of Medicine Elsea Lab
10:30 – 10:45 a.m.
Questions for Session 1 Talks
10:45 – 11:00 a.m.
Break Coffee and refreshments available
SESSION II
___________________
11:00 – 11:25 a.m.
Relation between the location of TCF4 mutations and the severity of intellectual disability Mari Sepp, PhD Department of Gene Technology Tallinn University of Technology Timmusk Lab
11:25 - 11:50 a.m.
TCF4 mutation confers a general deficit in prefrontal network activity. Huei -Ying Cheng Lieber Institute for Brain Development Johns Hopkins Medical Campus Maher Lab
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___
___
11:50 – 12:15 p.m.
Gene Therapy for Central Nervous System Diseases Steven Gray, PhD Gene Therapy Center University of North Carolina, Chapel Hill
12:15 – 12:30 p.m.
Questions for Session 2 Talks
12:30 – 1:30 p.m.
Lunch
SESSION III
______________________________________________
1:30 – 1:55 p.m.
Virtual Collaborations for Developing Treatments on a Shoestring Sean Ekins, PhD, D. Sc. Collaborations Pharmaceuticals, Inc
1:55 – 2:20 p.m.
Exploration of Development, Behavior, and Autism Symptom Profiles in Individuals with Pitt-Hopkins Syndrome Sarah O’Kelley, PhD
University of Alabama, Birmingham 2:20 – 2:50 p.m.
Update and findings from Pitt Hopkins Clinic, UTSW Sailaja Golla, M.D. University of Texas Southwestern Medical Center
2:50 – 3:05 p.m.
Questions for Session 3 Talks
3:05 – 3:20 p.m.
Break
SESSION IV
____________________________________ __________
3:20 – 3:35 p.m.
EEG and ERP in TCF4 Mutant Mice Craig Powell, MD, PhD, FAAN, FANA Departments of Neurology & Neurotherapeutics, Psychiatry University of Texas Southwestern Medical Center
3:45 – 4:00 p.m.
Using computational methods to understand possible mechanisms causing TCF4 to lose function Bennett Gould presented by Sofia Pauca High school student, senior Alexander Lab, Wake Forest University
4:00 – 4:15 p.m.
Registry Update Jessica Fletcher Pitt Hopkins Research Foundation
4:15 – 4:25 p.m.
Questions for Session 4 Talks Adjourn
5:30 – 7:30 p.m.
Evening Reception for researchers and families Warwick Melrose Hotel, cocktail reception researchers and families 3015 Oak Lawn Ave Dallas, Texas 75219
Friday, November 4 th, 2016
_____
Conference site:
Embassy Suites, Love Field, Dallas, TX
8:30 – 8:45 a.m.
Welcome Audrey Davidow Lapidus
__
3880 West Norhwest Highway, Dallas, TX, 75220
President, Pitt Hopkins Research Foundation Board of Directors
LAY TALKS & PARENT INFORMATION
___________________
8:45 – 9:00 a.m.
Genetics 101 Andrew Kennedy, PhD
9:00 – 9:15 a.m.
The Case for HDAC Inhibition Andrew Kennedy, PhD
9:15 – 9:30 a.m.
Validating SCN10a antagonists as a treatment for Pitt Hopkins Syndrome Brady Maher, PhD Lieber Institute for Brain Development Johns Hopkins Medical School
9:30 – 9:45 a.m.
Gene to phenotype correlations in Pitt Hopkins Syndrome Mari Sepp, PhD Tallinn University of Technology, Estonia
9:45 – 10:00 a.m.
Gene Therapy in Central Nervous System Diseases Steven Gray, PhD University of North Carolina, Chapel Hill
10:00 – 10:30 a.m.
Break
10:30 – 11:00 a.m.
Hope on the Horizon — Updates on Angelman and Rett Research Rebecca Burdine, PhD and Daniel Tarquinio, DO, MS-CI RSRT Rett Clinic
Atlanta, Georgia 11:00 – 11:15 a.m.
Lab to Trial Norbert L. Wiech, PhD Consultant for Orphan Drug Development at Lysomics Therapeutics and Chromatin Therapeutics
11:15 – 11:30 a.m.
Metabolic Profiles of Pitt Hopkins patients, a case study report Sarah Elsea, PhD
Baylor College of Medicine 11:30 – 11:45 a.m.
Parent Registry Update Jessica Fletcher
Pitt Hopkins Research Foundation 11:45 – 12:15 p.m.
Treatable Metabolic Disorders Associated with Autism Spectrum
12:30 p.m.
Lunch
1:00 – 2:00 p.m.
Intro / Strengthening relationships when children have special needs Nick Martin
2:00 – 3:30 p.m.
Mom Break-Out Group
3:30 – 4:30 p.m.
Dad Break-Out Group
4:30 – 5:15 p.m.
Feeling better When We Feel Bad
5:30
Closing Remarks
5:30 – 6:00
Sibling Break-Out Group
Disorders John Slattery, BA, CCRP Clinical Research Program Manager Autism Research Program Arkansas Children’s Research Institute University of Arkansas
Supper on your own 8:30 p.m.
Cocktail hour at Embassy Suites bar
Saturday, November 5th, 2016______________________________________ Texas Trekkers Walk
Flag Pole Hill, White Rock Lake
8:00 a.m.
On-site Registration
9:00 a.m.
Walk/Fun Run Begins
10:00 a.m.
Games/Raffles/Activities
11:00 a.m.
Lunch
12:00 p.m.
Closing Remarks ~Location Change for PM programming~
AAC Conference
Embassy Suites, Love Field, Dallas, TX
1:30 – 2:00 p.m.
Intro - A parent’s journey to AAC Keisha Tipton, Rylee_Tipton, and Jessica Fletcher
2:00 – 3:30 p.m.
Group Sessions Session A - Intro to AAC Lucas Steuber Session B – Rylee's A-Z Literacy Plan Rylee Tipton
3:30 – 3:40 p.m.
Break
3:40 – 5:00 p.m.
Alternating Break Out Groups (will attend both) Session A - Organize high tech devices and Session B - Organize low tech talk boards
5:00 – 5:30 p.m.
Question and Answer Session
3880 West Norhwest Highway, Dallas, TX, 75220
Dinner at Rafa's restaurant - All the proceeds from the day will be donated to the Pitt Hopkins
Research Foundation! You can stop in for supper any time during the evening. Since we have such a large crowd, we will need to stagger times. THANK YOU RAFA'S!!!
Participant Biosketches Elsea Lab Sarah H. Elsea, PhD, FACMG
Associate Professor
BMGL Senior Division Director, Biochemical Genetics Dept. of Molecular and Human Genetics Baylor College of Medicine
One Baylor Plaza, NAB 2015 Houston, TX 77030
713-798-5484 (office) elsea@bcm.edu Dr. Sarah H. Elsea is an Associate Professor of Molecular and Human Genetics at Baylor College of Medicine and is Senior Division Director of Biochemical Genetics at Baylor Miraca Genetics Laboratories. Dr. Elsea received a B.S. in chemistry with a minor in biology from
Missouri State University and a Ph.D. in biochemistry from Vanderbilt University. She completed postdoctoral fellowships in molecular and biochemical genetics at the Baylor College
of Medicine and is a board certified geneticist through the American Board of Medical
Genetics and Genomics. She has held faculty appointments at Michigan State University and the Medical College of Virginia at Virginia Commonwealth University.
Her research is
focused on the discovery, pathomechanisms, diagnosis, and treatment of rare disease,
particularly neurodevelopmental disorders. She is a member of several professional societies and has authored more than 80 scientific and lay articles. Joseph Alaimo, PhD Postdoctoral Research Associate
Department of Molecular and Human Genetics
Jan and Dan Duncan Neurological Research Institute
Baylor College of Medicine
1250 Moursund Street, Suite N1050 Houston, TX 77030
Dr. Alaimo is a postdoctoral research associate in the department of Molecular and Human
Genetics at Baylor College of Medicine in Dr. Sarah Elsea’s laboratory. He completed his PhD work in molecular biology and genetics where his research efforts focused the identification and characterization of genetic mutations contributing to alcohol-use disorders. His current work is
targeted towards understanding the common cellular aspects and molecular pathways underlying overlapping phenotypes among neurodevelopmental disorders including SmithMagenis syndrome, Pitt-Hopkins syndrome, Prader-Willi syndrome, fragile X syndrome and 2q23.1 deletion/duplication syndromes.
Gray Lab Steven Gray, Ph.D. Assistant Professor
Gene Therapy Center
Carolina Institute for Developmental Disabilities Department of Ophthalmology
University of North Carolina at Chapel Hill
Dr. Steven Gray earned his Ph.D. in molecular biology from Vanderbilt University in 2006, after receiving a B.S. degree with honors from Auburn University.
He performed a
postdoctoral fellowship focusing on gene therapy in the laboratory of Jude Samulski at UNC. He is currently an assistant professor at UNC in the Department of Ophthalmology. He is also a member of the Gene Therapy Center and the Carolina Institute for Developmental Disabilities (CIDD).
Dr. Gray’s core expertise is in AAV gene therapy vector engineering, followed by
optimizing approaches to deliver a gene to the nervous system or eye. His major focus is in AAV vector development to develop vectors tailored to serve specific clinical and research applications involving the nervous system or eye. These include the development of novel AAV capsids amenable to widespread CNS gene transfer or specialized ocular gene
transfer. As AAV-based platform gene transfer technologies have been developed to achieve
global, efficient, and in some cases cell-type specific CNS gene delivery, his research focus has
also included preclinical studies to apply these reagents toward the development of treatments
for neurological diseases. Currently these include preclinical studies for Rett Syndrome, Giant Axonal Neuropathy (GAN), Tay-Sachs, Krabbe, AGU, and Batten Disease, and have expanded into human clinical studies to test a gene therapy approach for GAN.
Dr. Gray has published over 50 peer-reviewed papers in journals such as New England
Journal of Medicine, Molecular Therapy, Nature Biotechnology, Gene Therapy, and The Proceedings
of the National Academy of Sciences. He also has 3 pending patents. His research is funded by the
National Institute for Neurological Disorders and Stroke, as well as numerous large and small research foundations. Dr. Gray was recently recognized with the 2016 Healthcare Hero award
by the Triangle Business Journal, and his work on GAN was featured in a story by the CBS National Evening News in 2015. Contact information: Office: 919-962-2565
Lab: 919-962-2566
Email: graysj@email.unc.edu
http://www.med.unc.edu/genetherapy/research-laboratories/gray-lab
Kennedy Lab Andrew John Kennedy, Ph.D. Assistant Professor Bates College
E-mail: akennedy@bates.edu Dr. Kennedy’s research goal is to understand the chemical mechanisms that encode and maintain long-term memory, and
how these mechanisms have become dysregulated in intellectual
disability. His laboratory investigates how learning imprints information onto the epigenome of participating neurons, and how these biochemical pathways can be manipulated to enhance cognition in cases of intellectual disability. Currently, the lab studies the basic neurobiology
underlying Pitt-Hopkins Syndrome, an ultra-rare intellectual disorder on the autism spectrum
caused by the haploinsufficiency of transcription factor 4 (Tcf4). Additionally, the lab designs,
synthesizes, and evaluates neuroepigenetic therapeutics that alter histone acetylation or DNA methylation of plasticity-related genes to improve learning and memory in disorders marked by impaired memory function.
Maher Lab Brady J. Maher Ph.D. Lead Investigator
Lieber Institute for Brain Development Assistant Professor
Department of Psychiatry and Behavioral Sciences; Department of Neuroscience Johns Hopkins School of Medicine E-mail: brady.maher@libd.org
Dr. Maher's lab is interested in understanding the cellular and circuit pathophysiology that underlies
neurodevelopmental and psychiatric disorders. Recent progress in clinical genetics has led to the
identification of genetic variation and genes that are associated with these disorders. However, information about the function of many of these genes during neurodevelopment and in the adult brain is lacking. His group focuses on trying to understand the function of these risk genes by manipulating their expression level in utero during the peak of cortical development. His lab then use a variety of
approaches and technologies to identify resulting phenotypes and molecular mechanisms including cell and molecular biology, optogenetics, imaging, and electrophysiology.
Philpot Lab Ben Philpot, Ph.D.
Kenan Distinguished Professor
Associate Director, UNC Neuroscience Center Department of Cell Biology & Physiology
Dr. Ben Philpot earned his Ph.D. in psychobiology from the University of Virginia in 1997. He performed a neuroscience postdoctoral fellowship in the laboratory of Dr. Mark Bear at
Brown University and M.I.T., before coming to UNC in 2004. He is currently a Kenan Distinguished Professor in the Department of Cell Biology and Physiology, Associate Director of the UNC Neuroscience Center, and a member of the Neurobiology Curriculum and the
Carolina Institute for Developmental Disabilities (CIDD). Dr. Philpot is the co-Director of a cross-disciplinary postdoctoral training grant for the CIDD. Dr. Philpot has been a Simons
Foundation Investigator since 2008, and is additionally funded by the Angelman Syndrome Foundation, the Rett Syndrome Research Trust, the Pitt-Hopkins Research Foundation, the
National Institute of Mental Health, and the National Institute for Neurological Disorders and Stroke.
He was an instructor for the Neural Systems and Behavior summer course at the
Marine Biological Laboratories in Woods Hole from 2001-2004, and in his own lab he has
successfully mentored >20 graduate students and postdoctoral fellows. Dr. Philpot studies basic mechanisms of cortical plasticity during critical periods of brain development. His recent
research has focused on identifying the synaptic basis and therapeutic approaches for treating monogenic neurodevelopmental disorders.
Dr. Philpot has >70 peer-reviewed scientific
publications in prestigious journals such as Nature, Nature Neuroscience, Neuron, Cell, PNAS,
and the Journal of Neuroscience. He has won a number of awards, including the Dr. Claudia Benton Award for Scientific Research, the NARSAD Young Investigator Award, and a Whitehall Foundation fellowship. Contact information:
Neuroscience Research Building, Room 5119 115 Mason Farm Rd., Campus Box 7545 UNC School of Medicine
Chapel Hill, NC 27599-7545 Telephone (office): 919-966-0025 Telephone (lab): 919-966-0031
Website: https://philpotlab.org/ Email: bphilpot@med.unc.edu
O’Kelley Lab Sarah O’Kelley, PhD Assistant Professor
University of Alabama at Birmingham Department of Psychology
Community Health Services Building (19th St) 307U (205) 975-5781
Dr. O’Kelley is the Director of the Autism Spectrum Disorders (ASD) Clinic at UAB CivitanSparks Clinics; she is also involved in psychology and interdisciplinary clinical training as the
UAB LEND training director. She currently serves as leader of a state work group focused on Developmental Screening and Surveillance for Autism Spectrum Disorders (Act Early
Alabama state team). Her clinical interests include cognitive and diagnostic assessment, individual and group therapy approaches, and school consultation for children with ASD and
other neurodevelopmental disabilities. Dr. O’Kelley is a certified provider of the PEERS program
developed
at
email: PEERS@uab.edu).
UCLA
(for
more
information
about
UAB
PEERS
Dr. O'Kelley has been involved in research and clinical activities with individuals with ASD
and their families for 15 years. She completed her predoctoral internship at the University of
Alabama at Birmingham Psychology Internship Training Consortium, and was a LEND postdoctoral fellow at UAB Civitan-Sparks Clinics. From 2006 to 2008, a portion of her
postdoctoral fellowship included a position of Program Coordinator for the University of Alabama Autism Spectrum Disorders College Transition and Support program (UA-ACTS), a
program she helped develop and implement. Dr. O’Kelley is a member of the International
Society for Autism Research and American Psychological Association and is active in the Alabama Autism Providers Network.
Powell Lab Craig M. Powell, MD, PhD, FAAN, FANA
Ed and Sue Rose Distinguished Professor in Neurology Associate Professor
Section Head of Neurodevelopmental Disorders Department of Neurology & Neurotherapeutics Department of Psychiatry
Neuroscience Graduate Program University of Texas Southwestern Medical Center Dr. Powell is an Associate Professor with Tenure of Neurology and Psychiatry at UT Southwestern Medical Center who offers expertise in preclinical models of autism and intellectual disability and more recently in clinical studies of these conditions. Dr. Powell’s work characterizing genetic models of autism and intellectual disability based on Neuroligin 3,
Neuroligin 1, Neurexin 1, PTEN, Shank3 and other genetic causes has provided novel insights into the pathophysiology of autism and novel therapeutic targets for autism and intellectual disability. Indeed, his studies have led to the initiation of an NIH-funded clinical study of an
FDA approved drug for a genetic cause of autism. Dr. Powell’s recent inroads into translating preclinical treatments into actual patients provides a road map for future studies using animal models of Pitt Hopkins Syndrome to identify novel biomarkers and treatments for patients and their families.
Contact Information:
5323 Harry Hines Blvd. Dallas, TX 75390-8813 (214) 648-3529 office
craig.powell@utsouthwestern.edu
Timmusk Lab Tonis Timmusk, Ph. D. Professor
Chair of Molecular Biology Department of Gene Technology Tallinn University of Technology Akadeemia tee 15
19086 Tallinn, Estonia
E-mail: tonis.timmusk@ttu.ee Telephone: +372 620 4444, Fax: Phone: +372 620 4400 Dr. Timmusk is a molecular neurobiologist with research interests in gene regulation and signaling in the nervous system. In addition, his research investigates mechanisms of nervous system diseases, such as the neurodegenerative disorders Huntington’s and Parkinson’s diseases
and more recently also schizophrenia and mental retardation. Studies of Dr. Timmusk’s research group have contributed to the understanding of the function and signaling of nerve
growth factor (NGF) and glial-cell derived neurotrophic factor (GDNF) family ligands and receptors and to activity-dependent transcriptional mechanisms that underlie nervous system function in health and disease. His laboratory uses wide array of methods of molecular and cell biology, biochemistry, primary neuronal cultures and animal models, including transgenic mice. Recently his lab has started to study the function and mechanism of action of the bHLH transcription factor TCF4, the gene of which is mutated in Pitt-Hopkins syndrome (PTHS). Mari Sepp, Ph.D. Research scientist, Timmusk lab E-mail: mari.sepp@ttu.ee
My research interests focus on transcriptional dysregulation in
neurodevelopmental and neurodegenerative diseases, and activitydependent gene regulation in the nervous system. I have
investigated the functions of transcription factor 4 (TCF4) in health and disease by characterizing human TCF4 gene structure
and TCF4 expression at mRNA and protein level, studying the functional characteristics and
regulation of alternative TCF4 isoforms in non-neural cells and neurons, and determining the
impact of Pitt-Hopkins syndrome and non-syndromic intellectual disability associated mutations on TCF4 functions. I am currently studying the mechanisms underlying
neuronal activity-dependent regulation of TCF4 as well as its target genes in neurons in order to better understand its role in cognitive diseases and in the functioning of the nervous system
in general. I believe that a more precise understanding of the mode of how TCF4 is regulated
in neurons opens up opportunities for target identification for possible therapeutic intervention in Pitt-Hopkins syndrome.
Student Scientists Sofia Pauca
High School Student Junior Scientist Milligan Lab, Wake Forest University Email: sofia.tcf4@gmail.com I am a high school senior who is extremely interested in neurobiology research. During my freshman and sophomore years, I worked as a volunteer researcher in the Milligan Lab, Department of Neuroscience, Wake Forest University. My 10 year old brother
Victor has Pitt Hopkins, and because of him I have been inspired to conduct research concerning his syndrome. During this research, we performed a histological and
immunohistological study of the transgenic TCF4 and wild type mouse brain. In middle
school, I also conducted a three year research project on autism (specifically Fragile X) in drosophila melanogaster with Dr. Bill Connor from WFU. Two of these years, I received first place in Biology in the North Carolina State Science Fair. This past summer, I was selected as
a Summer Intern at the National Institutes of Environmental Health Sciences, Raleigh, NC, in Dr. Patricia Jensen's Developmental Neurobiology Lab. My research focused on deciphering
the role of norepinephrine in neocortical development. I am currently continuing this research throughout the year, and have been invited back as an intern for next summer. I hope to do
similar research in the future, and eventually go into this field as a career. Thank you to everyone who has helped me on my scientific journey so far, especially my family. Bennett Gould Student Scientist High school student, senior Alexander Lab, Wake Forest University Email: goulbp16@wfu.edu
I am a high school student studying Pitt-Hopkins Syndrome. I have been working in the Alexander lab at WFU for the past 6 months; Dr. Alexander runs a biochemistry lab focused on aminoacyl TRNA synthetases (AARS), but one of the tools she uses is molecular dynamics. I studied the effects of a single missense mutation (A587P) generated in TCF4 on conformational change and flexibility of the TCF4:NEUROD2 pseudo homodimer. Molecular dynamics simulations were run for 85 ns and in triplicate. Moving forward, I hope to continue work on this project by using graphic processing units (GPUs) to extend the timescale for the simulations to 10 ÉĽs. I would like to thank Dr. Mari Sepp for sending me the PDB of the pseudo homodimer that is originally from Dr. T. Ellenberger. Moreover, this would not have been possible without Dr. Rebecca Alexander, Lindsay Macnamara (PhD candidate), Dr. Cho, and the Pauca family.
Other Contributors Sean Ekins Ph.D., D.Sc.
CEO, Collaborations Pharmaceuticals, Inc.
5616 Hilltop Needmore Road, Fuquay Varina, NC 27526 USA (215) 687-1320
collaborationspharma@gmail.com
http://www.collaborationspharma.com/
Sean graduated from the University of Aberdeen; receiving his M.Sc., Ph.D. in Clinical
Pharmacology and D.Sc. in Science. He was a postdoctoral fellow at Lilly Research
Laboratories. He has worked as a senior scientist at Pfizer, Lilly, Associate Director of Computational Drug Discovery at Concurrent Pharmaceuticals Inc. (now Allergan), and Vice
President of Computational Biology at GeneGo (now Thomson Reuters). Sean is Adjunct
Professor, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill; Adjunct Associate Professor, School of Pharmacy Department of Pharmaceutical Sciences, University of Maryland and Adjunct
Professor in the Department of Pharmacology at Rutgers University– Robert Wood Johnson Medical School, Piscataway, NJ. Sean is currently co-founder and CEO at Phoenix Nest focused on Sanfilippo Syndrome rare disease drug discovery and Founder and CEO and founder of Collaborations Pharmaceuticals,
Inc. which is focused on rare and infectious diseases. He is also the CSO of the Hereditary
Neuropathy Foundation which is dedicated to support research on Charcot-Marie-Tooth and related neuropathies. He has been awarded 11 STTR/ SBIR grants and 1 R21 NIH grant as well as consultant on many others. He is currently PI on 4 active NIH grants funded by NINDS, NIAID and
NCATS. He has authored or co-authored >270 peer reviewed papers and book chapters, edited 4 books and his research is focused on collaborations to facilitate rare and neglected disease drug
discovery.
Some
of
his
online
contributions
can
http://www.collabchem.com Twitter: http://twitter.com/collabchem
be
found
here:
Blog:
Contact information: Sean Ekins
Collaborations Pharmaceuticals, Inc., 5616 Hilltop Needmore Road, Fuquay-Varina, NC 27526, USA.
Phoenix Nest, P.O. BOX 150057, Brooklyn NY 11215, USA.
Hereditary Neuropathy Foundation, 432 Park Avenue South – 4th floor,New York, NY 10016, USA.
Sailaja Golla, MD
Assistant Professor
Neurodevelopmental Pediatrics, Division Of Pediatric Neurology University of Texas Southwestern Medical Center
Children's Medical Center, Ambulatory Care Pavilion in Dallas 2350 Stemmons Frwy, Dallas TX 75207
Email: Sailaja.Golla@utsouthwestern.edu Dr. Sailaja Golla started as faculty at UT Southwestern Medical Center and Children's Health after completing pediatric neurology and neurodevelopmental disabilities training in July 2010.
Dr Golla’s research interests include translational research involving biomarkers and clinical
research related to autism and rare autism variants. She has won many awards including Teva Neuroscience award, America’s Best Physician’s award,Texas Super doctor award.
She is the director of the rare disease clinic at UTSW including Pitt Hopkin Clinic at UT Southwestern Medical Center
She has participated in multiple clinical trials including the Buspirone trial for Autism, a multicenter drug therapy trial. This is published in the Journal of Pediatrics. Her role in the study was acknowledged in an appendix of the manuscript. Other multi-center drug trials she has been part of include “Early Pharmacotherapy guided by Biomarkers in Autism” and “A
randomized, double-blind, placebo-controlled trial using Arbaclofen in Fragile X”, biomarkers
in Phelan-McDermid syndrome, a rare autism variant. She has also been invited to be the site-
PI for an NINDS/NeuroNEXT funded, multi-center trial looking at the effects of AFQ056
(study drug) on language learning in children with Fragile X syndrome
She has multiple publications in the field of intellectual disability and autism, she has also contributed to book chapters in the field of Autism. She has co-authored manuscripts
describing molecular and clinical analyses of FOX1 and CDKL5 mutations. She has collaborated with the intensivists and neonatologists to study long-term neurodevelopmental
outcomes in children receiving extra-corporeal life support. She co-authored a manuscript looking at the role of transcranial doppler in assessing cerebral blood flow, hemodynamics and metabolism in patients on extracorporeal life support. She is also collaborating with
cardiothoracic surgeons and cardiac intensivists to study neurodevelopmental outcomes in children with congenital heart disease. She has presented multiple abstracts at annual meetings
of Child Neurology Society and American Epilepsy Society, looking at seizures in children with autism spectrum disorder and EEG evolution. In summary, Dr Golla has brought exceptional quality and national recognition to the University Of Texas Southwestern School
Of Medicine with her outstanding clinical, research and advocacy based work. She is only one
of 2 people in the division with training in pediatrics, pediatric neurology and neurodevelopment.
John Slattery, BA, CCRP
Twitter: Follow on Twitter LinkedIn: Visit Profile
Email: JCSlattery@uams.edu Since 2011 John has been the lead clinical research program
manager and head of operations for clinical trials focused on Autism Spectrum disorder (ASD) and other neurodevelopmental disorders that are conducted in the Autism Research Program (ARP) at Arkansas Children’s
Research Institute (ACRI). John authored or has co-authored many peer-reviewed scientific
manuscripts, written detailed procedural guides for how to conduct pediatric clinical research, organized and created the First International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism Spectrum Disorder in 2014 and has been invited to
write a book chapter summarizing the usage of N-acetylcysteine (NAC) in neuropsychiatry
which is currently being compiled. Prior to his work at ACRI he was employed in Philadelphia, PA doing functional brain imaging research at the University of Pennsylvania investigating the
neural correlates of attentional networks after a traumatic brain injury or cerebrovascular accident and neuromodulatory and neurotherapeutics to try and enhance recovery. He is also the head of operations for a small startup company in Little Rock, AR focused on connecting
active and health conscious people to engage and interact through a proximity based mobile application and is a city organizer for entrepreneurial efforts in Little Rock, AR.
Norbert L. Wiech, PhD
Consultant for Orphan Drug Development at Lysomics Therapeutics and Chromatin Therapeutics
Dr. Norbert Wiech is the founder of Lysomics, LLC. and Chromatin Therapeutics, LLC to develop treatments for rare diseases based on epigenetic targeted pharmacology.
His
undergraduate and graduate degrees were obtained at the University of Notre Dame and doctorate in biochemistry from Tulane University. After graduation he was appointed as a corporate fellow at the Harvard School of Public Health which was pioneering nutritional studies related to cardiovascular diseases. He has more than forty years of experience in the pharmaceutical industry as a researcher, manager and an executive. He participated in the pre-
clinical product development and in the clinical development group for several “first of a class� of treatments.
He founded his first company in 1992 and shortly thereafter in 1994 a second company
Pharmaceutics International to provide contract pharmaceutical product development services and served as its CEO until 1998. In 1995, he became the CEO of the orphan drug company,
Ucyclyd Pharma. Under his leadership, Ucyclyd obtained FDA approval for the orphan drug
product Buphenyl, a brand of sodium phenylbutyrate for the treatment of the rare disease urea cycle disorders.
After the sale of Ucyclyd, he was asked to participate in a range of management roles to
advance the discovery and development of histone deacetylase inhibitors in privately held biopharmaceutical operations. As an adjunct at Notre Dame, he funded the start-up of the
HDAC program to investigate the potential of these novel drugs to treat neurological disorders
which led to start of a clinical trial to treat Niemann Pick Type C. He teaches and mentors in a
program to introduce undergraduate science majors to entrepreneurship in particular for Orphan Drugs.
Abstracts Title: The Case for HDAC Inhibition
Andrew Kennedy, PhD Bates College
Targeting histone deacetylases (HDACs) to enhance synaptic plasticity and broadly improve cognition has been established in disease and disorder model systems, as well as in neurotypical mice. Here, we
demonstrate that targeting HDACs using small molecule inhibitors may be a viable path to improving
cognition in Pitt-Hopkins Syndrome, by demonstrating their efficacy to improve learning and memory
in a Tcf4 (+/-) mouse model. Using next generation sequencing, we have identified downstream targets of HDAC inhibition in the hippocampus of Tcf4 (+/-) mice. We have also developed a novel
therapeutic that specifically targets HDAC2, an isoenzyme in the HDAC family that has been
demonstrated to be a negative regulator of learning and memory, and we have begun a systematic
evaluation of its long-term efficacy. These data suggest HDAC inhibition is a viable clinical option for
Pitt-Hopkins Syndrome.
Lay Talk: The Genetics of Pitt-Hopkins Syndrome
Pitt-Hopkins Syndrome is caused by a mutation in or a deletion of Transcription Factor 4 (Tcf4). But
what does Tcf4 do in the body and in the mind? And why does the loss of Tcf4 function cause Pitt-
Hopkins? We’ll be discussing what we know about the genetics of Pitt-Hopkins, as well as the
approaches Pitt-Hopkins researchers are taking to understand what the loss ofTcf4 means for the brain
and how it might be treated.
Title: Regulation of TCF4 transcriptional activity in neurons Mari Sepp and TĂľnis Timmusk
Department of Gene Technology, Tallinn University of Technology
Calcium-dependent gene expression in neurons is one of the mechanisms by which neuronal plasticity, enabling higher organisms to learn from and adapt to environment, is achieved. We
have identified TCF4 as a neuronal activity and calcium-dependent transcriptional activator in
neurons, providing insights into the mechanisms that underlie Pitt-Hopkins syndrome
(PTHS), a complex disorder caused by mutations in one of the TCF4 alleles and characterized
by severe intellectual disability (ID) and autistic-like behaviour. We and others have recently
demonstrated that, in addition to PTHS, mutations in TCF4 gene give rise to milder, nonsyndromic ID. The position of the mutation in TCF4, a gene with complex organization and
multiple transcription initiation sites, is relevant to the phenotype, supporting the notion that precise regulation of TCF4 expression levels and the correct dose of its alternative isoforms are critical for correct brain development and function. Notably, our results from fruitflies show that proper expression of TCF4 is crucial for survival even after development has been completed.
To understand the role of TCF4 in the neuronal activity-regulated transcription comprehensive
knowledge about its signal-dependent regulation mode, functionally important protein regions, and target genes is required. Therefore, in the current study we aimed (1) to further delineate the steps that lead from increase in cellular calcium and/or cAMP to activation of TCF4-
mediated transcription in neurons, (2) to analyze the functional impact of newly identified TCF4 mutations/variations associated with PTHS, mild to moderate ID and schizophrenia,
(3) and to identify neuronal activity-regulated TCF4 target genes using whole transcriptome analysis.
Title: Relation between the location of TCF4 mutations and the severity of intellectual disability
Mari Sepp and TĂľnis Timmusk
Department of Gene Technology, Tallinn University of Technology
TCF4 gene codes for numerous TCF4 protein isoforms of different length. All isoforms contain the sequences coded by downstream part of the TCF4 gene while only the longer
isoforms contain sequences coded by the upstream part of the gene. Mutations in one of the
two gene copies of TCF4 are usually associated with Pitt-Hopkins syndrome (PTHS) that features severe intellectual disability. However, some TCF4 mutations have also been linked to
milder non-syndromic intellectual disability. We propose that rather than the mutation type
(e.g deletion vs. point mutation) the position of the mutation in TCF4 gene is relevant to the disease severity. PTHS-associated mutations are located in the downstream part of the gene and affect all TCF4 isoforms. Milder phenotypes are elicited by mutations that locate to the
upstream part of the TCF4 gene and leave shorter TCF4 isoforms intact, or by certain small
mutations in regions not affecting the important functional domains of TCF4 protein. Altogether, it is possible that a continuum of phenotypes from mild intellectual disability to
PTHS are caused by different TCF4 mutations with the outcome depending on the number of remaining intact TCF4 isoforms produced from the mutation-carrying TCF4 gene copy.
Title: Virtual Collaborations for Developing Treatments on a Shoestring
Sean Ekins, PhD
Collaborations Pharmaceuticals, Inc., Hereditary Neuropathy Foundation
Phoenix Nest (http://www.phoenixnestbiotech.com/) was co-founded with a rare disease parent (Jill Wood 1) and is working on treatments for Sanfilippo syndrome (MPS III), a
devastating neurodegenerative lysosomal storage disorder of childhood. In the space of 4 years, we have built up collaborations with leading academics and industry and submitted multiple NIH small business technology transfer (STTR) grant proposals. We completed our first phase I NIH NINDS STTR in 2015 grant to fund development of an enzyme replacement therapy with our academic collaborator (LA BioMed) for MPS IIID (an ultra-rare disease). More
recently we obtained phase II funding for this project such that we have been awarded ~$1.75M total. In addition, we have recently obtained a second Phase I grant ($250K) to
develop a stem cell/ gene therapy treatment for MPS IIIB. Our focus for return on investment
is the rare pediatric disease priority review voucher from the FDA 2. I will highlight our evolving, lean company strategy, which enables a small virtual team to coordinate and leverage
the academic research resources that have been accumulated. I will summarize our collaborative strategy and efforts to partner with global groups to pursue additional treatments for MPS III
e.g. gene therapy, chaperone therapy for MPS IIIC. I have recently founded a second company (Collaborations Pharmaceuticals, Inc. (http://www.collaborationspharma.com/) to address other rare and neglected diseases and was recently awarded an STTR with Rutgers University
to work on treatments for tuberculosis ($150K) 3. I am currently working on projects with
several university collaborators and licensing compounds and technologies. At a bare minimum, other rare and neglected diseases could leverage this approach 4. To do this, they require at least
one scientist with whom you can submit grants and papers, and ultimately, licensing what comes out of the work will be just as important to aid in funding further development. We
would encourage other scientists to collaborate with small companies like these to further the
research on their diseases. From my experiences, this has lead to creation of jobs, funding for academic labs and moving potential treatments closer to the clinic. 1.
Wood J, Sames L, Moore A, Ekins S, The multifaceted roles of rare disease parent / patient advocates in drug discovery, Drug Disc Today, 18: 1043–1051, 2013. http://www.drugdiscoverytoday.com/download/1215
2.
Ekins S and Wood J, Incentives for starting small companies focused on rare and neglected diseases, Pharm Res, 33(4):809-15 2016.
3.
Riccardi G, Old IG, Ekins S, Raising awareness of the importance of funding for tuberculosis small molecule research, Drug Disc Today, In Press. 2016.
4.
Ekins S, Diaz N, Chung J, Matthews P and McMurtray A, Enabling anyone to translate clinically relevant ideas to therapies, Pharm Res, In Press 2016.
Title: Treatment Avenues for Pitt Hopkins Syndrome Brady J. Maher1,2,3
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 2Department of
1
Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD,
3
Department of
Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD
Pitt Hopkins Syndrome (PTHS) is a rare autism spectrum disorder that results from mutation in Transcription Factor 4 (TCF4) and for which no specific treatment is known. My
presentation will focus on recent work in my lab aimed at developing novel treatments for PTHS. I will focus on our recent identification of SCN10a, a voltage-gated sodium channel, as
a potential therapeutic target. Several pharmaceutical companies have developed compounds that specifically target SCN10a for the treatment of pain, and one of these compounds has passed Phase I, but failed in Phase II because it did not reduce the sensation of pain. We are
now testing this compound for efficacy at rescuing behavioral deficits in our PTHS mouse model and I will discuss the results of these studies as well as our plans to repurpose this
compound for treatment in PTHS. In addition, I will discuss our research program aimed at using patient derived induced pluripotent stem cells (iPSCs) and human neurons to identify novel therapeutic targets and to translate our findings from rodent models into a human model.
Title: TCF4 mutation confers a general deficit in prefrontal network activity.
Huei-Ying Chen1, Greg R. Hamersky1, Joseph Bohlen1, Brent Mayfield1, Morganne N.
Campbell1, Stephanie Cerceo Page1, Brady J. Maher1,2,3
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD,
1
2
Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD,
3
Department of
Department of
Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD
Pitt-Hopkins Syndrome (PTHS) is a monogenic neurodevelopmental disorder caused by autosomal dominant mutation in TCF4. The underlying pathophysiology generated by haploinsufficiency of TCF4 protein remains unclear. Previous work on prefrontal layer 2/3
pyramidal neurons found an abnormal membrane firing property in TCF4+/tr mice, which model PTHS. This deficit is partly due to ectopic expression of two ion channels including
SCN10a and KCNQ1 in excitatory neurons. Multiple studies have identified an imbalance of excitatory and inhibitory synaptic transmission in several different animal models of psychiatric
disorders. Therefore, we hypothesize that the decreased excitability observed in prefrontal
neurons in the PTHS mouse will negatively impact network activity levels and lead to a decrease in spontaneous excitatory and inhibitory synaptic transmission. To test this hypothesis,
we characterized the spontaneous synaptic transmission onto prefrontal layer 2/3 pyramidal
cells by whole-cell patch clamp in TCF4+/tr and wildtype littermates. We found both spontaneous excitatory postsynaptic current (sEPSC) and inhibitory postsynaptic current (sIPSC) frequencies are reduced in TCF4+/tr mice compared to controls. However, we saw no
effect on the frequency or amplitude of miniature EPSCs or IPSCs that were measured in the
presence of TTX. This differential effect on spontaneous versus miniature synaptic transmission is indicative an overall decrease in network activity. In addition, we characterized parvalbumin (PV) positive fast spiking interneurons (FS) in our PTHS mouse model and observed no changes in the intrinsic excitability or the frequency and amplitude of sEPSCs
onto FS cells. However, the sIPSC frequency was significantly lower in TCF4+/tr mice. Together, our data suggests that the prefrontal cortex of our PTHS mouse shows a general deficit in network activity that may contribute to the pathophysiology of PTHS.
Title: Gene Therapy for Central Nervous System Diseases
Steven J. Gray, PhD
Gene Therapy Center, Carolina Institute for Developmental Disorders, and Dept. of Ophthalmology
University of North Carolina, Chapel Hill, NC, USA
Gene therapy for central nervous system (CNS) disorders has seen a recent resurgence with the
discovery of adeno-associated virus (AAV) vectors that are capable of crossing the blood-brain barrier (BBB), such as AAV9. The Gray lab has been focused on examining the translational
potential of AAV9 to treat inherited CNS disorders. Initial studies demonstrated that AAV9 can achieve dose-dependent, widespread gene transfer to neurons and astrocytes in mice as well
as in non-human primates. However, several details hampered the clinical translation of this approach including: high vector doses (manufacturing burden), presence of natural anti-AAV
neutralizing antibodies in some individuals, and high peripheral organ gene transfer potentially causing gene-dependent toxicity. Nonetheless, at least 2 clinical trials have been initiated using
AAV9 vectors injected intravenously, for Spinal Muscular Atrophy and Mucopolysaccharidosis
Type IIIA. In lieu of an intravenous route of administration, intrathecal administration of AAV9 also leads to broad CNS gene transfer in mice, pigs, and non-human primates, but overcomes some of the limitations associated with intravenous administration.
Using AAV9-mediated gene transfer as a platform approach to treat an inherited CNS
disease, we have initiated preclinical studies for Giant Axonal Neuropathy (GAN), Batten
Disease, Aspartylglucosaminuria, Tay-Sachs disease, Krabbe disease, and Rett syndrome.
Based on encouraging preclinical data showing reduce pathology and increased rotarod function in GAN mice, along with favorable safety data, a clinical trial was initiated in May 2015 at the
NIH Clinical Center to test intrathecal administration of scAAV9/JeT-GAN in patients with
GAN. Using the same approach, encouraging preclinical data has been generated for each of
the other diseases with efforts underway to translate the treatments for Krabbe disease and
Batten disease to human trials. A pilot study to assess the feasibility of gene therapy for PittHopkins is underway.
Title: Convergent evidence for hippocampal NMDA receptor hyperfunction in PTHS Ben Philpot, PhD
Associate Director, UNC Neuroscience Center Department of Cell Biology & Physiology, University of North Carolina, Chapel Hill
There are no treatments for the core symptoms of PTHS, which result from haploinsufficiency of the transcription factor, TCF4. The hippocampus, an important brain region for learning and memory, expresses particularly high levels of TCF4 and has reduced volume in PTHS
individuals, suggesting that dysregulation in this region dictates many PTHS core phenotypes.
Little is known about the synaptic and cellular hippocampal functions affected by TCF4 loss, which has impeded the rational development of PTHS therapeutics, especially those that could overcome the debilitating learning difficulties. Our lab has generated multiple mouse models
of PTHS, including a “first of its kind� model carrying the highly prevalent, pathogenic human R580W mutation within the basic helix-loop-helix region of TCF4 (mouse Tcf4R579W). Our
data from these models indicate that loss of TCF4 function leads to weight loss, low anxiety, hyperactivity, and poor spatial memory (a hippocampal-dependent task). Our data, from four
separate PTHS mouse models, also show that TCF4 loss inappropriately enhances the induction of hippocampal long-term potentiation (LTP), likely due to selectively increasing
synaptic NMDA receptor (NMDAR) currents, while other synaptic measures appear normal. Our observations are consistent with anecdotal reports that NMDAR antagonists (e.g. Amantadine)
provide
therapeutic
benefits
to
PTHS
individuals.
Title: Large-scale untargeted metabolomics profiling in Pitt-Hopkins syndrome uncovers phenotypic-associated amino acid and lipid abnormalities Joseph T. Alaimo and Sarah H. Elsea
Department of Molecular and Human Genetics Baylor College of Medicine
Transcription factor 4 (TCF4) encodes a helix-loop-helix transcription factor that, when
haploinsufficient, results in the neurodevelopmental disorder Pitt-Hopkins syndrome (PTHS). PTHS is characterized by severe intellectual disability, absent speech, seizures, breathing
abnormalities, behavioral problems, and delayed motor milestones in which more than half fail
to walk independently. In addition, natural variation at this locus is associated with the complex
disease schizophrenia. The phenotypic spectrum associated with TCF4 variation suggests a unique role for the protein in pathways mitigating neurodevelopment and cognitive function;
therefore, we sought to undercover functional pathways regulated by TCF4 through the application of a small molecule metabolomics screen. We examined plasma samples of 13 individuals with a molecularly confirmed diagnosis of PTHS that were predominately male and
ranged in age from 1.5 to 20 years. Our cohort had a history of global developmental delay, absent or sparse speech, seizures and sleep anomalies. Metabolomic profiles from this cohort were significantly enriched for alterations in lipid and amino acid associated pathways. All
individuals displayed abnormal lipid profiles, but consistent alterations were observed in fatty
acid and phospholipid metabolism. We identified elevated oleamide levels, an endogenously
metabolized fatty acid amide associated with sleep problems, a phenotypic feature of our cohort. In addition, abnormalities across palmitic acid metabolism and utilization were
identified, including elevated palmitic amide a known marker for schizophrenia. Amino acid abnormities were observed across 12 of 13 samples with consistent alterations found in pathways associated with oxidative stress and mitochondria function, such as methionine
sulfoxide and N-acetylaspartate. Interestingly, 3 individuals within our cohort displayed alterations in carnitine metabolism suggesting carnitine biosynthesis defects and were recommended for further clinical testing. Taken together, the application of metabolic profiling in individuals with PTHS suggests that TCF4 plays a functional role in small molecule
pathways that may contribute to the phenotypic features of the disorder. Future studies
discerning the cellular defects associated with these metabolic alterations will likely present new opportunities for therapeutic interventions in PTHS.
Title: Exploration of Development, Behavior, and Autism Symptom Profiles in Individuals with Pitt-Hopkins Syndrome
Sarah E. O’Kelley1, Kristi Carter Guest1, Elizabeth Rahn1, Andrew Kennedy2, & J. David Sweatt3
University of Alabama at Birmingham, Department of Psychology, 2Bates College, 3Vanderbilt University,
1
Department of Pharmacology
Available clinical studies describe individuals with Pitt-Hopkins Syndrome (PTHS) as exhibiting some of the core symptoms of Autism Spectrum Disorder (ASD), including
difficulties in verbal and nonverbal communication, sensory sensitivity, and social interaction difficulties. Significant developmental delays, including motor delays, and intellectual disability are also reported in individuals with PTHS. The current studies focused on obtaining
demographic information as well as standardized caregiver-report measures of development,
behavior, and ASD symptoms to clarify and characterize the presence of ASD symptoms in
this population, with particular emphasis on the social, communication, adaptive, developmental, and repetitive behaviors of individuals with PTHS. Information regarding
ASD symptoms and patterns of behavior within genetic syndromes such as PTHS may be helpful in characterizing a broader ASD phenotype. Further, a better understanding of social
communication and behavioral difficulties in individuals with known genetic differences and developmental delays may help guide more informed recommendations for intervention.
Parent/caregiver participants were recruited through the Pitt Hopkins Research Foundation and completed questionnaires over the telephone and by mail, including a detailed
demographic and background questionnaire, the Modified Checklist for Autism in ToddlersRevised (M-CHAT-R), Communication and Symbolic Behavior Scales-Infant Toddler Checklist (CSBS-ITC), Repetitive Behavior Questionnaire (RBQ), Short Sensory Profile-2 (SSP-2), and Vineland Adaptive Behavior Scales- II. Additional measures of behavioral
difficulties were also obtained. To date, 29 families have completed measures for this study
with children with PTHS ranging in age from 11 months to 19 years old, with initial data indicating developmental delays across skill areas. Over half of respondents reported tantrums
in their children but aggression towards others was much less frequent. Nearly all individuals with PTHS were engaged in intervention services including special education support,
speech/language, physical, and/or occupational therapies. On rating scales, individuals with PTHS were described as exhibiting delays in early emerging social-communication skills on the
CSBS-ITC and the presence of significant ASD “red flags� on a brief screening tool developed for very young children. On the RBQ, a tool that has demonstrated good validity in measuring
repetitive behaviors in several genetic syndromes as well as ASD, individuals with PTHS received elevated scores for overall repetitive behaviors and in particular, the presence of clinically significant stereotyped behaviors. A range of sensory differences in comparison to
children without developmental delays were also endorsed by caregivers on the SSP-2. Future
directions will include more specific, direct observations of skills and behaviors in individuals
with PTHS utilizing standardized assessments specific to cognitive skills and ASD symptoms to obtain more detailed information.
Notes
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