UPenn’s 2016 Million Dollar Bike Ride Pilot Grant Program is now open! The Pitt Hopkins Research Foundation has participated every year, since the start of this incredible program. The MDBR Pilot Grant Program provides a one-year grant to support research related to a rare disease represented in the 2016 Million Dollar Bike Ride. Number of awards and dollar amounts vary per disease based on fundraising totals by each disease team.
Eligibility: All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.
Submit your Letter of Interest (LOI) via the link below no later than Friday, September 16, 2016 by 8pm EST.
Study Identifies Potential Treatment for Autism Spectrum Disorder
Lieber Institute investigators designed an innovative methodology that identifies the first potential treatment for Pitt-Hopkins syndrome, a type of autism.
10 March 2016
BALTIMORE—March 10, 2016—The Lieber Institute for Brain Development (LIBD) released today the results of an innovative study that may lead to a clinical trial within a relatively short time for the treatment of Pitt-Hopkins syndrome (PTHS), a type of autism spectrum disorder.
There are currently no medications available to treat the cognitive and behavioral deficits associated with PTHS, which is characterized by intellectual disability, developmental delays and communication deficits. The Lieber Institute’s study is the first to identify specific proteins that represent potential therapeutic targets for Pitt-Hopkins and possibly other neuropsychiatric disorders, including other forms of autism and schizophrenia. Lieber Institute scientists show that by modifying these proteins, abnormalities related to the Pitt-Hopkins gene are reversed.
The study, published today in the journal Neuron, is titled “Psychiatric Risk Gene Transcription 4 Regulates the Intrinsic Excitability of Prefrontal Neurons via Repression of SCN10a and KCNQ1.” The paper can be found online here http://www.cell.com/neuron/fulltext/S0896-6273(16)00138-0.
In contrast to prior strategies for finding treatments for autism, which have mainly focused on trying to correct the genetic abnormality itself, Lieber Institute scientists took a novel approach to understand the mechanism responsible for the cognitive and behavioral deficits. In genetically modified rats, they identified abnormalities in brain cell function after birth that are potentially responsible for the cognitive and social abnormalities. Specifically, they found an ion channel protein not normally present in the brain to be overly active, disrupting nerve cell function. This particular ion channel is normally controlled by Transcription 4 (TCF4), the gene that is mutated in Pitt-Hopkins. When they administered drugs targeting this and another disrupted ion channel, or when they used genetic editing approaches to render the channels less active, the abnormal brain cells were restored to normal.
“These findings are a significant step toward developing effective treatments for Pitt-Hopkins and potentially other autism spectrum disorders,” said Brady J. Maher, Ph.D., the study’s lead investigator. “The results suggest that giving a drug that will block these ion channels in patients with Pitt-Hopkins could make their cells behave normally again.”
Pitt-Hopkins is caused by mutations of the gene TCF4. Because it is a monogenic disorder (caused by a single gene), scientists can effectively identify the underlying biology of the disorder in animal and cell models. Researchers at the Lieber Institute used CRISPR/Cas9 gene editing technology and short hairpin RNA to specifically target TCF4 function in an in vivo rodent model of Pitt-Hopkins. They also developed a novel technique called iTRAP to identify the culprit ion channels in the central nervous system, specifically SCN10a and KCNQ1, as candidate genes for targeted therapy.
“We are strongly encouraged by the results of this study and are moving forward with a series of experiments designed to further characterize the therapeutic target that we have identified at the cellular level,” said LIBD Director and CEO Daniel R. Weinberger, M.D. “We are exploring approaches for a therapeutic trial in individuals with this condition. Drugs that block these channels already exist, so this is a rare opportunity to go from the laboratory to the clinic in relatively short order.”
This work was supported by the Lieber Institute as well as NIH/NIMH grants (K01MH086050 and R56MH104593), a NARSAD Young Investigator Grant and a Pitt-Hopkins Research Foundation Grant awarded to Maher, the study’s lead investigator.
About the Lieber Institute for Brain Development
The mission of the Lieber Institute for Brain Development and the Maltz Research Laboratories is to translate the understanding of basic genetic and molecular mechanisms of schizophrenia and related developmental brain disorders into clinical advances that change the lives of affected individuals. LIBD is an independent, not-for-profit 501(c)(3) organization and a Maryland tax-exempt medical research institute affiliated with the Johns Hopkins University School of Medicine.
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Media Contacts
Amy Snow Landa or Aaron Blank, The Fearey Group for the Lieber Institute
The Pitt Hopkins Research Foundation is thrilled to announce our 2016 Grant Awardees. Three grants were given at 75K each by the PHRF, and two grants were given through the University of Pennsylvania, Million Dollar Bike Ride, at 50K each. A total of $325,000 was awarded for Pitt Hopkins research this year:
Tilly Hadlow Young Investigator Award:
Joseph Alaimo, Ph.D., Principal Investigator; Sarah Elsea, Ph.D., Co-Investigator/Mentor, Baylor College of Medicine, Awarded $75,000, PHRF
Delineating Therapeutic Targets using Global Metabolic Profiling in Pitt Hopkins syndrome: Defining the cellular defects due to alterations in TCF4 function is paramount in order to determine the proper molecular and biochemical targets for therapeutic intervention in Pitt-Hopkins syndrome. To identify and characterize the biochemical and molecular dysfunction due to altered TCF4 function, we plan to take a clinical and translational approach by recruiting a cohort of individuals with PTHS in collaboration with the Pitt-Hopkins Research Foundation and current PTHS clinics, phenotypically and molecularly characterizing the cohort, and employing state-of-the-art metabolomics screening to identify pharmacologically targetable molecular and biochemical pathways. Our unique approach will utilize a special type of biochemical genetic test called global metabolomics assisted pathway screening (Global MAPS). Global MAPS is currently the most comprehensive small molecule screen available in the clinical setting and is only available through Baylor College of Medicine’s Biochemical Genetics Diagnostic Laboratory. Global MAPS surveys greater than 1000 small molecules in human plasma, pinpointing defects in pathways unmeasurable by standard clinical testing methods, offering a comprehensive and in-depth analysis of patient samples and metabolic status. Our overall goal is to employ Global MAPS analysis in patients with PTHS to identify novel pathway alterations and to understand the basis of TCF4 function in cells. In addition, our proposal will serve as a functional confirmation of current molecular findings in PTHS research, including RNA-sequencing and gene expression profiling, thereby refining the molecular and biochemical targets that would benefit most from therapeutic intervention. Our novel but complementary approach will promote additional analysis to identify points of data convergence among other research groups thereby expediting the process toward targeted therapeutic intervention and clinical trials. Any Pitt-Hopkins families interested in participating in metabolomics profiling are highly encouraged to contact either Drs. Sarah Elsea or Joseph Alaimo at Baylor College of Medicine using the following information: email: Alaimo@bcm.eduPhone: 832-824-8936
Benjamin D. Philpot, Ph.D., Principal Investigator; Alexander D. Kloth, Ph.D., Co-Principal Investigator; Courtney L. Thaxton, Ph.D., Co-Principal Investigator, The University of North Carolina at Chapel Hill, Awarded $75,000, PHRF
Characterization and Generation of PTHS Model Mice for Rational Therapeutic Discovery:Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder characterized by intellectual disability, absent speech, seizures, ataxia, and breathing anomalies. In support for future therapeutic development for PTHS, we will pursue two independent aims: (1) to uncover the neural impairments that are common across multiple PTHS mouse models, and (2) to develop new tools to analyze TCF4 expression in neuronal subtypes throughout development and adulthood. In the first aim, we will follow up on our finding that long-term changes in synaptic function related to experience are enhanced in multiple PTHS-related mouse models. We hypothesize that this deficit is related to altered function of a glutamate receptor, the NMDA receptor, and we will rigorously test this hypothesis using electrophysiology, biochemistry and pharmacological methods in multiple PTHS-related mouse models. In the second aim, we will develop a unique mouse model toward determining effective drug targets that affect TCF4 expression levels, as well as be able to alter TCF4 activity in a spatiotemporal manner. This novel binary “reporter-reinstatement” mouse will not only allow for a stream-lined and genetically precise approach to drug discovery for PTHS, but also will allow us to determine the most efficacious time in which to reinstate TCF4 function to alleviate the pathophysiologies associated with PTHS. In all, the proposed project pursues incisive approaches that will provide guidance to the development of PTHS therapeutics.
Kindal Kivisto Award for Promising Young Researchers:
Andrew John Kennedy, Ph.D., Principal Investigator; J. David Sweatt, Ph.D., Co-Principal Investigator, Evelyn F. McKnight Brain Institute, The University of Alabama at Birmingham, Awarded $75,000, PHRF
Investigating Therapies for Pitt-Hopkins Syndrome:The central strategy of our research program consists of two goals: the near-term goal to identify FDA approved drugs as potential translatable therapies for Pitt-Hopkins Syndrome (PTHS) and the long-term goal to develop novel neuroepigenetic therapies that fundamentally reverse the effects of PTHS. Over the past three years, we have characterized a genetically engineered heterozygous deletion mouse model of PTHS (Tcf4 +/-), validated the histone deacetylase enzyme Hdac2 as a target to treat the cognitive deficits associated with PTHS, and undertaken a drug screening program. This grant will investigate the efficacy of Fingolimod (trade name Gilenya), as well as other FDA approved therapeutics that target Hdac2, to improve learning, problem solving, and associative memory in PTHS mice. These experiments will focus on identifying a plausible drug candidate that can be translated to a clinical setting and effectively improve cognition in PTHS patients. Additionally, more advanced epigenetic therapies will be developed to address the genetic cause of PTHS. Every person has two functioning copies of Tcf4 with the exception of individuals with PTHS, who have a mutation or deletion that yields only one functioning copy. Epigenetic therapies, which alter the epigenetic states at specific genes within the genome, are being designed to allow PTHS models to use their one functioning copy of Tcf4 twice as much, hopefully restoring full Tcf4 function and reversing the cognitive deficits associated with Pitt-Hopkins. Taken together, these approaches investigate already-available FDA approved drugs and cutting edge genetic techniques to identify potential therapies that improve cognition in the near-term and attempt to address and compensate for the underlying cause of Pitt-Hopkins Syndrome.
Brady Maher, Ph.D., Principal Investigator; Huei-Ying Chen Ph.D.; Stephanie Cerceo-Page, Ph.D.; Lieber Institute for Brain Development, Johns Hopkins School of Medicine, Awarded $50,000, UPenn, MDBR
Exploring the impact of a TCF4 mutation on the physiology of inhibitory neurons of the prefrontal cortex:PTHS is a neurodevelopmental disorder due to mutation or deletion of one copy of the TCF4 gene. TCF4 is a transcription factor that can regulate the expression of many downstream genes and therefore regulates the genetic programs necessary for normal brain development. We measured the expression of TCF4 mRNA across the lifespan in humans and rodents and observed a peak in TCF4 expression occurs during the formation of the cerebral cortex, a region of the brain important to higher cognitive functions including learning and memory. Using a mouse model of PTHS that has a mutation in one copy of the TCF4 gene, we observed that TCF expression is blunted during the developmental peak in expression compared to control animals, and we believe this indicates a causal time period for the development of PTHS. Unfortunately, this critical period occurs in utero and prior to when diagnosis is currently made, thus complicating our ability design treatment strategies during this causal phase of the disorder. Therefore, our research group is focused on understanding the underlying pathophysiology that produces symptomatology in PTHS so that we can normalize this pathophysiology in children and adults. Using our animal models of PTHS, we have identified a sodium channel that is normally expressed in the peripheral nervous system, but is ectopically expressed in the central nervous system when TCF4 is mutated. Experiments are currently underway to determine if blocking this Na channel with drugs can lead to improvement on behavioral tests in our PTHS mouse model. In our current proposal, we would like to follow up a preliminary result that suggests inhibitory transmission onto excitatory neurons in the cortex is decreased in the PTHS mouse compared to control littermates. In addition, using RNA sequencing of the PTHS mouse model we observed that many genes that are specific to inhibitory neurons show decreased expression compared to control animals, and we identified a specific population of inhibitory neurons (cortistatin positive) that normally show high levels of TCF4 expression. These cortistatin positive interneurons are known to release a neuropeptide called cortistatin that has been shown to inhibit the generation of seizures and regulate sleep states. Given the prevalence of seizures and sleep disturbances in PTHS, we believe this population of inhibitory neurons may underlie clinical aspects of the disorder. Therefore, we propose to breed the PTHS mouse with another mouse that allows us to visualize cortistatin positive interneurons and we will use electrophysiology and microscopic imaging to determine if these cells are disrupted in the PTHS mouse model compared to control littermates. If deficits are observed in this population we will determine the cellular and molecular mechanism using pharmacological rescue and/or molecular phenocopy. Identified molecular mechanisms will then be deemed potential therapeutic targets and these targets will be tested for their ability to normalization of behavioral deficits in the PTHS mouse.
Tõnis Timmusk, Ph.D., Principal Investigator; Mari Sepp, Ph.D., Co-Investigator, Tallinn University of Technology, Estonia, Awarded $50,000, UPenn, MDBR
Regulation of TCF4 transcriptional activity in neurons: Transcription factor TCF4 (alias ITF2, SEF2 or E2-2) is a broadly expressed protein involved in the development and functioning of many different cell types. Recent studies point to important roles for TCF4 in the nervous system. Specifically, human TCF4 gene is implicated in susceptibility to schizophrenia and mutations in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare developmental disorder characterized by severe motor and mental retardation, typical facial features and breathing anomalies. The mutation may be in different parts of the gene, but it appears in only one allele. Whereas in many other genes the other, unaffected allele would be able to compensate for the defect, this is not the case in TCF4. This indicates that the protein encoded by the TCF4 gene is essential for the development of the nervous system, and that human development depends significantly on the amount of this protein in the brain and body. Our previous data have suggested that synaptic activation of nerve cells, that is the basis of brain function, leads to activation and phosphorylation of TCF4 protein. Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation turns many proteins on and off, thereby altering their function and activity. The current project is aimed to find out how the activity and phosphorylation of TCF4 protein is regulated inside nerve cells of the brain, and to characterize the phosphorylation pattern of activated TCF4. Additionally, we want to determine which genes are targeted by TCF4 in nerve cells after synaptic activation. Since Pitt-Hopkins syndrome manifests itself at an early stage, there are better chances for its treatment due to the greater plasticity of children’s brains. Increasing the amount and/or activity of the functional TCF4 protein produced from the healthy allele is among possible approaches to develop drugs for Pitt-Hopkins syndrome treatment. We believe that our project could lead to the discovery of novel possibilities for increasing the activity of TCF4 in nerve cells that could be useful to develop treatments for therapeutic intervention of Pitt-Hopkins syndrome.
This year, The PHRF is deeply moved to award the “Kindal Kivisto Award for Promising Young Researchers,” in honor of Kindal Kivisto a young woman who died far too soon, at the age of 29 this past October. Kindal did not have Pitt Hopkins, but was close friends with the Sandiford family whose daughter, Finley was diagnosed in 2014. In light of this, her family asked that all donations at the funeral be made to the Pitt Hopkins Research Foundation. The outpouring of love and support for this special young woman was overwhelming. A total of $25,000 was donated to the Pitt Hopkins Research Foundation in memory of Kindal. Her family wrote to us during this time, and we will never forget them saying that hoped some good could come of this tragedy.
So this year, in honor of Kindal and her family, we are awarding a grant to Dr. Andrew Kennedy of the The Sweatt Lab at The University of Alabama, Birmingham in her name, with the knowledge that the promise taken from her may in some small way be countered by the incredible hope and promise this young researcher creates for our families every day.
Kindal and Family… Thank you for making this possible for our children. You will not be forgotten.
https://pitthopkins.org/wp-content/uploads/2020/05/27574.png00PHRFhttps://pitthopkins.org/wp-content/uploads/2020/05/27574.pngPHRF2016-01-16 13:31:262018-06-02 02:05:18Kindal Kivisto Award for Promising Young Researchers
Thanks to everyone who helped make 2015 our best year yet. Let’s make 2016 even better!
2015 Fundraising totals are in, and they are Bigger Than EVER: $460,000
That’s $60 K more than last year and, this year we didn’t even have those amazing EASTSIDE high school kids (who brought in $130K) helping! So that means, as a group we brought in nearly$200K more than last year. More and more new families joined the effort and with a 75 percent increase in family involvement over last year!
2015 Accomplishments
There is a tremendous amount going on at PHRF; we are now supporting 7 research projects. When we started, just 3 years ago, there was virtually no laboratory research being done on this exceedingly rare disorder. This growth means more scientists are focusing on Pitt Hopkins; more labs are working together and sharing knowledge, ideas, and resources; and we are spurring a range of approaches to developing treatments and a cure for Pitt Hopkins. In short, it means we have more scientific momentum than ever towards what we all want—to change the lives of those who live every moment of every day with the debilitating symptoms of Pitt Hopkins.
Here are a few specifics on progress we have made this year in several key areas:
1. Reversal: Reversal projects target the underlying cause of Pitt Hopkins and have the greatest likelihood of having a profound impact on symptoms. Our lab at the University of Alabama Birmingham (UAB) has found a drug therapy that reverses the symptoms of Pitt Hopkins in mice! There is a similar, less toxic drug, currently being tested in the mice that may be contender for trials in the near future.
2. Treatment: Treatment projects seek to improve the quality of life for those with Pitt Hopkins by addressing one or more symptoms. This year the PHRF supported two studies at top labs (the Powell Lab at University of Texas Southwestern and the Katz Lab at Case Western University) looking at epilepsy and breathing issues. Currently our mouse models are being tested for seizure activity and hyperventilation. Once these studies are done we will know whether or not we have a legitimate target for testing treatment-centered therapeutics in the mice.
The Katz Lab at Case Western also studies breathing issues in Rett Syndrome mice, and they have brought a drug called Ketamine to trial this year in Rett Syndrome. This may be a possible target drug for our children as well. It’s too early for results on these trials, but we will share news as soon as we get them.
3. Clinics: The PHRF launched two dedicated Pitt Hopkins Clinics, one at UCSF in San Francisco and one at UT Southwestern in Dallas. We are also working with the National Institute of Mental Health to launch a Pitt Hopkins study site (Summer, 2016) where children from all over the world will be able to be seen at no cost. We hope to continue building this network of clinics around the world where doctors will share and update each other regularly on the latest and most effective medical practices for our children. These clinics and study sites will also be essential in helping develop a comprehensive natural history of Pitt Hopkins, a must for moving forward with clinical trials.
4. Basic science: To inform all our approaches for treating and hopefully curing Pitt Hopkins Syndrome, we must continue expanding our understanding of the neurobiology behind PTHS and the mutated Tcf4 gene that causes it. Our funded labs are doing exactly this and have made several discoveries, including the finding of dysregulated glutamate receptors. This led us to convince our Dallas clinic to try Amantadine, an already FDA approved NMDA receptor antagonist on some patients, and we are seeing some positive results, including increased focus and reduced hyperactivity.
5. Family Support: We held the first ever Science and Family Conference this September in Washington D.C. Families from all over the world joined together for the first time to hear from our scientists and clinics and to meet other members of our global Pitt Hopkins Family. We had no idea the impact this one weekend would make. We laughed, we cried, we cried some more, and we knew at the end of it all we could not wait TWO more years to see our Pitt Family again. We had originally thought the conference would be biannual. But it was clear, that as a fledgling and growing organization, we needed to do it again, as soon as possible.
MARK YOUR CALENDARS FOR Nov 5-7, 2016 Dallas, Texas!
6. AAC: We often hear from parents that one of the hardest parts of Pitt Hopkins is the lack of communication, particularly when our kids are suffering. This year we dove into learning more about Augmentative Alternative Communication and held our first AAC conference at the Science and Family Conference. Stay tuned for more of these in 2016.
7. Give Rare champions: We were crowned THE 2015 GIVE RARE CHAMPIONS. We raised $23,000 in ONE DAY and won 15K more in matching grants, beating out organizations far bigger than us!
WHO’S IN FOR GIVE RARE 2016? Email us at: phrf-fundraising@pitthopkins.org
8. Pinterest: We launched a Pinterest page to share ideas on everything from therapy to gluten free and dairy free desserts to what to buy for Pitt Christmas presents. Join us here.
9. Coriell Cell Bank: We launched the Coriell Cell Bank for Pitt Hopkins skin fibroblasts and plasma so that reseachers all over the world will have easier access to skin and blood cells for research. Email Nahid Turan nturan@coriell.org to start the donating process.
10. Registry: We created the global Pitt Hopkins Registry to gather information and help advance research more efficiently and faster. We have over 200 people registered so far! If you haven’t registered yet, you can do so here.
More families than ever were involved in making this the best year yet at the PHRF! If you are interested in getting involved, contact us at phrf-fundraising@pitthopkins.org.
The Pitt Hopkins Research Foundation hosted our second Scientific Symposium and first ever Parent Conference at American University in Washington D.C. September 10-12, 2015. It was a fantastic event, full of great information and a wonderful time for families to spend together. Thursday, September 10, researchers presented on their research including talks on Discovery of Compounds & Signaling Pathways Regulating TCF4 Expression in Human Stem Cell-Derived Neuronal Cell Models and Tcf4 regulates synaptic plasticity, DNA methylation, and memory function. The researchers were able to have open collaboration to develop strategic aims for the coming year. It was a very exciting and encouraging!
Friday researchers gave lay talks to parents and family members, the clinics and study site gave an update, and Dr. Kathleen Holton gave a talk on Potential Dietary Implications for Pitt Hopkins Syndrome. In the afternoon parents had break out sessions where we discussed the triumphs as well as frustrations that go along with Pitt Hopkins Syndrome. Speaking with other parents is an invaluable resource that we all were very grateful to experience.
Saturday was the AAC conference. Dr. Caroline Ramsey Musselwhite and Dr. Gretchen Hanser definitely did not disappoint! Many resources were shared and parents walked away with a wealth of knowledge on how to get started using AAC with their Pitt Hopkins children. A parent described this day as “life changing!”.
– 70+ PTHS family members
– 30+ scientists/researchers/doctors
– 5 pitt hopkins children/adults
– 4 different countries represented
To sum up the week, I love this quote from a parent who attended the conference…”These days with you guys were awesome and worth every penny, every minute in the air and all the logistic planning with people taking care of (our child) while we were gone. Thank you for the warm welcome and for having us, to be a part of the PTHS-community during these days was so great, to finally belong somewhere and finding hope, information and new friends who will understand. And although you are very far from us in distance, you are close to our hearts.” SCHEDULE: Wednesday evening, September 9th:
6:00pm-7:00pm: Meet and greet happy hour, Omni Shoreham Hotel — Marquee Bar and Lounge
2500 Calvert St NW, Washington, DC 20008
Thursday, September 10th: Full Day: Scientific talks from all six of our PHRF funded researchers.
8:30 – 9:15 a.m Breakfast in atrium of Mary Graydon Center of American University
9:00 – 9:10 a.m. Welcome, Audrey Davidow Lapidus, President, Pitt Hopkins Research Foundation
9:10 – 9:15 a.m. Opening Remarks, J. David Sweatt, Ph.D., Professor SESSION I, Session Chair: Krista Hennig, PhD
9:15 – 9:40 a.m. Meeting challenges in Pitt-Hopkins Syndrome and other neurodevelopmental disorders, Hazel Sive, PhD
9:40 – 10:05 a.m. Tcf4 regulates synaptic plasticity, DNA methylation, and memory function, Andrew Kennedy, Ph.D. (Sweatt Lab)
10:05 – 10:30 a.m. Identification of genetic and molecular targets for Pitt-Hopkins therapeutics, Courtney Thaxton, Ph.D. (Philpot 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, Session Chair: Andrew Kennedy, PhD
11:00 – 11:25 a.m. Uncovering altered gene expression pathways during neuronal development in Pitt-Hopkins syndrome, Sarah H. Elsea, PhD, FACMG
11:25 – 11:50 a.m. Toward Novel Therapeutics for Pitt-Hopkins Syndrome: Discovery of Compounds & Signaling Pathways Regulating TCF4 Expression in Human Stem Cell-Derived Neuronal Cell Models, Krista Hennig, Ph.D. (Haggarty Lab)
11:50 – 12:15 p.m. Transcription factor 4 (TCF4) Isoforms Regulate the Expression of Different Genes in Neuroblastoma cells, Daniel R. Marenda, PhD
12:15 – 12:30 p.m. Questions for Session 2 Talks
12:30 – 1:15 p.m. Lunch SESSION III, Session Chair: Courtney Thaxton, PhD
1:30 – 1:55 p.m. Transciption Factor 4 (TCF4) regulates the intrinsic excitability and spatial distribution of pyramidal neurons in the prefrontal cortex, Brady J. Maher, Ph.D., Assistant Professor
1:55 – 2:15 p.m. A Study of the Anatomical differences in the TCF4 Mouse Model of Pitt Hopkins Syndrome, Sofia Pauca
2:15 – 2:30 p.m. Questions for Session 3 Talks
2:30 p.m. Closing Remarks to the General Audience, Theresa Pauca, PHRF Vice President SESSION IV Break Out Collaboration Session, Session Chair: David Sweatt, PhD
3:00 – 4:15 p.m. Open collaboration session for all funded researchers to develop strategic priorities for Pitt Hopkins research. Interested researchers not funded by PHRF are encouraged to attend as well.
4:15 – 4:30 p.m. Brief presentation of experimental priorities and strategic aims for coming year
5:30 – 7:30 p.m. Hosted Cocktail Reception for families and researchers at Ardeo + Bardeo Restaurant–rooftop, 3311 Connecticut Avenue, Washington, DC 20008
Friday, September 11th:
Morning: Nontechnical (lay) talks by PHRF Researchers for families, updates by physicians from Pitt Hopkins Clinics, and parent question and answer session with researchers and physicians. Afternoon: Breakout sessions for parents.
8:30 – 8:40 a.m. Welcome, Audrey Davidow Lapidus, President, Pitt Hopkins Research Foundation SESSION I
8:45 – 9:05 a.m. Introduction to Genetics: The genetics of PTHS and genetically engineered mice, Andrew Kennedy, Ph.D. (Sweatt Lab), Department of Neuroscience and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham
9:05 – 9:15 a.m. Pitt-Hopkins Syndrome Stem Cell Models: From Families To The Future, Stephen Haggarty, PhD and Krista Hennig, Ph.D.
Massachusetts General Hospital, Harvard Medical School
9:15 – 9:25 a.m. Understanding gene expression pathways in Pitt-Hopkins syndrome, Joseph Alaimo, PhD (Elsea Lab), Department of Molecular and Human Genetics, Baylor College of Medicine
9:25 – 9:30 a.m. Questions
9:30 – 9:40 a.m. New views on genetic disorders: helpful lessons from the zebrafish, Jasmin McCammon, PhD (Sive Lab), Whitehead Institute
9:40 – 9:55 a.m. Questions
9:55 – 10:05 a.m. Searching for Seizures and Biomarkers of Brain Function in Pitt Hopkins Syndrome, Craig Powell, MD, PhD, FAAN, FANA, Departments of Neurology & Neurotherapeutics, Psychiatry, University of Texas Southwestern Medical Center
10:05 – 10:15 a.m. Using models of Pitt-Hopkins Syndrome to identify therapeutic targets, Brady Maher, PhD, Lieber Institute for Brain Development, Johns Hopkins Medical School
10:15 – 10:25 a.m. Questions
10:30 a.m. Break
10:45 – 11:00 a.m. Making Sense of Cognitive and Behavioral Testing in Pitt-Hopkins and other Neurogenetic Disorders, NIMH Pitt Hopkins Study Site, Drs. Audrey Thurm and Armin Razanahan, National Institute of Mental Health
11:00 – 11:30 a.m. Clinic Update/Q.A. Dr. Sailaja Golla, UT Southwestern
11:30 – 12:00 p.m. Potential Dietary Implications for Pitt Hopkins Syndrome, Kathleen Holton, PhD, MPH, Department of Health Studies, Center for Behavioral Neuroscience, American University
12:00 p.m. Lunch
1:00 – 1:50 p.m. Discussion, Q&A
1:50-2:00 p.m. Cyber Support, Sue Routledge
2:00 – 4:00 p.m. Parents’ Breakout Groups
4:00 p.m. Close
8:00 p.m. Cocktails at Bethesda Doubletree Hotel Bar
Saturday, September 12th:
Full Day: An incredible Literacy and Augmentative and Alternative Communication (AAC) conference taught by two of the best communication people in the business, Dr. Caroline Ramsey Musselwhite, Ed.D, CCC/SLP and Dr. Gretchen Hanser, PhD, OTR! This day is open to the general public at the speakers typical conference price of $100 per day. Saturday’s Topic: Literacy for All! Get Ready – Get Set – Read, Write, GO! When we say “all,” we mean “ALL.” ALL students can make progress with learning to read and write – including students who cannot talk and those who cannot hold a book or a pencil. Exciting research in the past two decades has found that with the right instruction and the right tools, students with significant disabilities can develop as readers and writers. This workshop will provide a broad overview of the “how.” A variety of meaningful reading and writing activities will be shown, with an emphasis on early literacy development. Augmentative & alternative communication (AAC), appropriate books, “alternative pencils” that don’t require hand use, and other forms of assistive technology will be highlighted throughout. Videos and work samples will be shown of real students. Sample goals and ways of assessing change will be shared.
A second day of AAC is offered on Sunday, at the same location, with Dr. Caroline Ramsey Musselwhite, Ed.D, CCC/SLP and Dr. Gretchen Hanser, PhD, OTR. The topic for this day is: Emergent Balanced Literacy And AAC – Apps Included.
EARN FREE REGISTRATIONS AND HOTEL STAYS **
All Pitt Hopkins families are invited to FUNDRAISE for the PHRF, to help offset some of the costs for the Symposium and/or Conference. In order to earn these rewards, email phrf-fundraising@pitthopkins.org by August 30, 2015 to register your qualified fundraiser. If you participate in another PHRF fundraising event and raise or donate a minimum of $1500 on your family’s behalf, you are eligible for these rewards, but you are responsible for tracking and submitting the donation receipts in one spreadsheet. The event organizer should not be held responsible. If multiple families are holding a joint event, the rewards for the amount raised will be split fairly among the families. Events including Give Rare or MDBR can be used to earn rewards, too. In the instance that one PTHS family holds a fundraiser to support another PTHS family and donates to the second families page, the fundraising dollars should go to the family who actually raised the money. Fundraising dollars are non-transferable. After the conference, please submit your receipts for registration and/or hotel room by October 1, 2015, and you will be reimbursed for these charges within one month, to phrf-fundraising@pitthopkins.org. If you have any questions at all, please feel free to email Audrey or Theresa at phrf-fundraising@pitthopkins.org.
• $1,500 – $2,499 raised earns one free registration day, and one night hotel stay
• $2,500 – $4,999 raised earns two free registration days, and one night hotel stay
• $5,000 – $7,499 raised earns one free registration day and two night hotel stay
• $7,500 – $9,999 raised earns two free registration days and two night hotel stay
• $10,000 and over raised earns three free registration days and three night hotel stay
**This applies to any fundraisers held in the 2015 calendar year.
https://pitthopkins.org/wp-content/uploads/2020/05/27574.png00PHRFhttps://pitthopkins.org/wp-content/uploads/2020/05/27574.pngPHRF2015-09-16 21:33:512018-06-02 02:08:282015 PHRF Symposium and Family Conference
September is such a big month for our community. Our third annual Pitt Hopkins Awareness Day was celebrated September 18, 2015. We have people from 28 different countries across the globe in our Pitt Hopkins family. On the 18th we honored our precious children together!
UCSF Benioff Children’s Hospital San Francisco has opened the third Pitt Hopkins Syndrome (PTHS) clinic in the world, giving patients with this rare genetic condition access to an interdisciplinary team of specialists, including neurologists, clinical geneticists, gastroenterologists and pulmonologists, and establishing a new platform-for advancing research on the disease.
The clinic, which will be conducted in collaboration with the Pitt Hopkins Research Foundation, exemplifies UCSF Medical Center’s mission of treating patients, working to identify new therapeutic approaches as they emerge, and conducting clinical research using patients’ genetic information to advance the field.
The clinic will be led by Elliott Sherr, MD, PhD, professor of pediatrics and neurology at UC San Francisco.
PTHS affects a specific gene in chromosome 18, and is associated with developmental delays, breathing problems, recurrent seizures and distinctive facial features. Children with PTHS often present a happy, excitable demeanor, with frequent smiling, laughter, and hand-flapping movements. However, they can also experience anxiety and behavioral problems, as well as cognitive disabilities.
“Bringing patients together with this rare condition will allow observations to come to the forefront that wouldn’t be able to if we didn’t have the opportunity to treat several dozen children with Pitt Hopkins simultaneously,” said Sherr. “Creating a specialty clinic enables our physicians to recognize the subtle details of this syndrome and develop a comprehensive plan for each patient with a focus on improving quality of life.”
The TCF4 gene that causes Pitt Hopkins Syndrome wasn’t discovered until 2007, when it was found to play an essential role in the development of the nervous system and the brain. Since 2007, genetic testing has become available, allowing doctors to diagnose patients with PTHS whose conditions were previously unexplained, and finally giving some parents answers after searching for a diagnosis for their children for years.
While the number of identified PTHS patients worldwide is approximately 500, experts believe that number is actually higher and many individuals remain undiagnosed.
Children and adults who are suspected of having a genetic syndrome, such as Pitt Hopkins, or a disorder with a genetic component are offered genetic screening at UCSF, including whole exome sequencing, a blood test that looks at more than 20,000 genes. The test focuses on exomes, the protein-coding portions of genes that account for only 1 percent of DNA but nearly 85 percent of the glitches known to cause human diseases.
The Pitt Hopkins clinic offers fully coordinated interdisciplinary care. Additionally, patients and families who elect to participate in research will be able to provide information regarding their conditions that will populate a large database enabling researchers to analyze genetic information and use this information as a starting point for the development of potential therapies. “Because we’re actively conducting research in the lab, as we make discoveries those advances get immediately applied to the patients in the clinics,” said Sherr.
“We are thrilled to have Dr. Sherr and his multidisciplinary team at UCSF leading our third clinic,” said Audrey Davidow, president of the Pitt Hopkins Research Foundation. “The UCSF staff care deeply about helping improve quality of life for individuals with rare disorders and we are extremely grateful that they are teaming up with our other clinics to bring the best level of care possible to individuals with Pitt Hopkins syndrome.”
UCSF is a leading university dedicated to transforming health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. Founded in 1864 as a medical college, UCSF now includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with world-renowned programs in the biological sciences, a preeminent biomedical research enterprise and top-tier hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals.
https://pitthopkins.org/wp-content/uploads/2020/05/27574.png00PHRFhttps://pitthopkins.org/wp-content/uploads/2020/05/27574.pngPHRF2015-09-07 16:04:042018-04-13 20:41:12Univ. of California-San Francisco opens Pitt Hopkins Clinic
Our Foundation’s motto is “We don’t just hope for Miracles. We fight for them.” So proud and gratified to have so many joining our fight. The University of Texas Southwestern Dallas clinic is now officially open — furthering our dream of a clinical consortium focused on Pitt Hopkins care.
Children’s Health opens new clinic specifically focused on treating and researching rare Pitt Hopkins Syndrome (PTHS)
DALLAS – Children’s Health announced today the opening of the second Pitt Hopkins Syndrome (PTHS) clinic in the nation. PTHS is a rare genetic condition affecting a specific gene in chromosome 18, called TCF4. PTHS is characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features.
The number of identified PTHS patients worldwide is approximately 500, however there are many who are believed to remain undiagnosed. The new clinic will be part of the Center for Autism and Developmental Disabilities (CADD) at Children’s Health.
“We are honored and privileged to launch the second clinic, solely devoted to PTHS in the nation at Children’s Health. The real aim of opening this clinic is to make life better for children living with this condition and to provide much-needed resources to their families as we continue to research the root of the condition and its impact,” explained Dr. Sailaja Golla, pediatrics, neurology and neurotherapeutics specialist at Children’s Health and assistant professor at UT Southwestern Medical Center.
Under the direction of Dr. Golla and the CADD and supported by the Pitt Hopkins Research Foundation, the clinic will focus on providing knowledge-based medical care and serving the comprehensive medical needs of children with PTHS. With the creation of the clinic, patients and their families will have access to multiple specialists and medical resources.
The Pitt Hopkins Research Foundation will provide its administrative structure, such as meeting planning and referrels, to the new Dallas clinic. Additionally, Children’s Health will be part of a group of medical institutions and clinicians devoted to learning more about Pitt Hopkins through the foundation’s devlopment of the Pitt Hopkins Clinic & Research Consortium.
“Our goal is that all families will have access to quality evaluation, treatment recommendations and care within a reasonable geographic distance from their homes. The Dallas clinic’s central location in the U.S. will hopefully allow families greater access to care from around the globe,” said Audrey Davidow, president of the Pitt Hopkins Research Foundation.
The first clinic was set up at Massachusetts General Hospital in Boston under the direction of Dr. Ronald Thibert and Dr. David Sweetser, and generously supported by Nancy LeGendre and Walter Herlihy, parents of two young women living with Pitt Hopkins Syndrome.
The new Children’s Health CADD clinic will provide coordinated care with access to a clinical geneticist, neurologist, psychologist, gastroenterologist and pulmonologist. Children’s Health is seeking to improve the health and quality of life for children with PTHS and to begin collecting a natural history of patients to further research the condition with the opening of the clinic.
Individuals living with PTHS may suffer from developmental delays, limited speech, low muscle tone, extreme breathing problems, seizures, gastrointestinal issues, and autistic or hyperactive behaviors including great excitability. Affected individuals have distinctive facial features, and many have limited mobility.
Genetic testing became available after discovery of mutations in the TCF4 gene as the cause of Pitt Hopkins Syndrome in 2007, but clinical suspicion for testing was limited to the most profoundly affected patients.
While most sequels disappoint, the second annual Million Dollar Bike Ride for Rare Diseases proved to be a huge success. A beautiful sunny day in Philadelphia was enjoyed by our incredible team of Pitt Hopkins Pedalers racers. And $40,000 was raised for scientific research! The icing on the cake — all will be matched dollar for dollar by the UPENN Center for Orphan Diseases. Thank you so much for everyone who rode, supported, volunteered or cheered from the sidelines — this was another amazing team effort!
https://pitthopkins.org/wp-content/uploads/2020/05/27574.png00PHRFhttps://pitthopkins.org/wp-content/uploads/2020/05/27574.pngPHRF2015-05-11 21:39:532018-06-02 02:10:53UPenn Million Dollar Bike Ride 2015
