Collaborative Drug Discovery Interview with Theresa Pauca,VP

“I think that right now there seems to be a really big push into research on rare diseases. All the rare diseases are collectively getting together and saying, “Hey, we’re here!” – combined together they make one big common type of genetic disease category. I think this is the day and age of rare diseases.” ~Theresa Pauca

Interview by: Whitney Smith, Director of Business Development, Collaborative Drug Discovery, June 2017:

This interview focuses on Theresa’s involvement with the Foundation and the work that we are doing to support research into Pitt Hopkins syndrome:

Spotlight Interview with Theresa Pauca, Co-founder and Vice President of the Pitt Hopkins Research Foundation

 

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We’re partnering with the Mighty!

We’re thrilled to announce a new partnership that will bring our resources in front of The Mighty‘s wide-reaching readership. We will now have our own growing homepage on The Mighty and appear on many stories on the site.

The Mighty is a story-based health community focused on improving the lives of people facing disease, disorder, mental illness and disability. More than half of Americans are facing serious health conditions or medical issues. They want more than information. They want to be inspired. The Mighty publishes real stories about real people facing real challenges.

Here’s an example of the kind of stories on The Mighty: What Does It Mean to Be ‘Rare’? You Told Us.

9 Oscar-Nominated Films That Got Disease and Disability (Mostly) Right

To the Person Who Called Me ‘the World’s Ugliest Woman’ in a Viral Video

6 Things to Remember as a Patient in the Undiagnosed Diseases Program

8 Things I Wish I Knew When My Child Was Diagnosed With a Rare Disorder]

We’re dedicated to helping people with Pitt Hopkins Syndrome in their lives. With this partnership, we’ll be able to help even more people.

We encourage you to submit a story to The Mighty and make your voice heard.

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2016: A YEAR OF UNPARALLELED GROWTH FOR THE PITT HOPKINS RESEARCH FOUNDATION

2016 has been a tremendous year for the Pitt Hopkins Research Foundation. We are now supporting 7 incredible research projects. When we started, just 4 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. Gene Therapy 

In the history books of science, 2016 will certainly be remembered as the year the hope and promise of gene therapy became a reality with successful trials in Batten’s Disease, Spinal Muscular Atrophy (SMA) and other rare diseases. Indeed, the SMA trial was so successful, it had to be discontinued as it was no longer ethical to continue giving placebo. The drug, Spinraza, was approved by the FDA just before Christmas.

The PHRF is wholeheartedly committed to staying abreast of the incredible progress in this arena. We were proud and grateful to fund our first gene therapy grant to Dr. Steven Gray at the University of North Carolina, Chapel Hill this year, the same Dr. who made the cutting edge breakthroughs in Batten’s disease possible.

2. Reversal

Reversal projects target the underlying cause of Pitt Hopkins and have the greatest likelihood of having a profound impact on symptoms. Our pioneer researcher, Dr. David Sweatt, left the University of Alabama Birmingham (UAB) this summer to head the prestigious pharmacology department at Vanderbilt University. Likewise, Andrew Kennedy, the primary post doc in the Sweatt Lab studying Pitt Hopkins, has moved on to start his own lab, dedicated primarily to Pitt Hopkins, at Bates College.  This team has found a drug therapy that reverses the symptoms of Pitt Hopkins in mice— and now they are spreading this important work to these stellar new labs across the country.

Read more about their work in this scientific article published, August 2016, in Cell. 

In 2017, we plan to test more compounds with similar mechanisms to see if other, more easily administered, drugs might offer a similar effect and begin the process of moving towards clinical trials.

3. Treatment

Treatment projects seek to improve the quality of life for those with Pitt Hopkins by addressing one or more symptoms. Last 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. While the mice did not show breathing issues, they did show reduced seizure threshold. This epilepsy study, out of the Powell Lab also revealed an important biomarker we are readying to explore in 2017. Biomarkers are essential for successful clinical trials, and much of our work in 2017 will be devoted to establishing effective biomarkers.

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.

4. New mouse models

Dr. Ben Philpot at UNC successfully created a third Pitt Hopkins mouse model — known as a “knock in”.  This mouse will help determine effective drug targets that affect TCF4 expression levels, as well as be able to alter TCF4 activity at different points in development—an important step to ascertain whether treatments will be beneficial at different stages of development. 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.

5. Clinics

The  two dedicated Pitt Hopkins Clinics, one at UCSF in San Francisco and one at UT Southwestern in Dallas, continue to grow their patient population and share treatment protocols which may benefit 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.

6. 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. We hope to publish a paper on this with Dr. Sailaja Golla from the Dallas Clinic this year.

Dr. Tonis Timmusk at the Talinn Institute of Technology in Estonia continues to investigate increasing the amount and/or activity of the functional TCF4 protein produced from the healthy allele. We believe that this 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.

Dr. Brady Maher, from the Lieber Institute also published his work, funded by the PHRF, in March of this year, an explosive report highlighting the important role of dysregulated calcium and potassium channels in Pitt Hopkins. This work offers important insight into drug targets we are pursuing in 2017.
Read more about Dr. Maher’s work here.

7. Family Support

The 2nd Science and Family Conference was held in November in Dallas, Tx. More than 200 people from around the world  joined together to hear from our scientists and clinics and to meet other members of our global Pitt Hopkins Family. We laughed, we cried, we cried some more, and we are already busy planning the next one, tentatively set for summer 2018. 

8. 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 continued our commitment to educating families about Augmentative Alternative Communication and held our second AAC conference at the Science and Family Conference.

9. Coriell Cell Bank

We grew and expanded the Coriell Cell Bank for Pitt Hopkins skin fibroblasts and plasma so that researchers all over the world will have easier access to skin and blood cells for research. More than 20 families participated in the blood draw at our annual conference. This important project is ongoing — please email Nahid Turan nturan@coriell.org if you are interested in starting the donation process.

10. Registry

We now have nearly 250 families in the global Pitt Hopkins Registry to gather information and help advance research more efficiently and faster. If you haven’t registered yet, you can do so here.

11. Mitochondrial assessment

Further pursuing the evidence of mitochondrial defects in our children, Dr. Michael Goldenthal at Drexel University and Dr. Richard Frye at the University of Arkansas launched a buccal swab collection. More than 20 families at the conference participated in this study aimed at revealing common mitochondrial defects in our children that may be able to serve as biomarkers in future clinical trials. This study is ongoing and you can still participate by e-mailing Michael.Goldenthal@DrexelMed.edu.

More families than ever were involved in making this the best year yet at the PHRF! We need your help–please contact us at phrf-fundraising@pitthopkins.org today! 

HERE’S TO A 2017 FULL OF HOPE AND DISCOVERY!

 

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Ann D. Bornstein Gene Therapy Grant

This year, The PHRF is deeply moved to award the “Ann D. Bornstein Gene Therapy Grant,” in honor of Ann Bornstein, aunt of PHRF president, Audrey Davidow Lapidus, and sister of PHRF board member Jeffrey Davidow, who passed unexpectedly earlier this year. The Bornstein family has been extremely generous to the Foundation over the years and without them, so much of our research would not be where it is today. When she passed, her family asked that donations be made to the Pitt Hopkins Research Foundation. The outpouring of love and support for this special woman was overwhelming. And a generous amount was raised in her memory.

So this year, in honor of Ann and her family, we are awarding a grant to Dr. Ben Philpot and Dr. Steven Gray at the University of North Carolina, Chapel Hill with the hope that the grief of her passing may in some way be countered by the promise they are creating for our families through Gene Therapy.

Grant summary

The laboratories of Dr. Ben Philpot and Dr. Steven Gray at the University of North Carolina at Chapel Hill are collaborating on a project to investigate the feasibility of a gene therapy approach for Pitt-Hopkins syndrome (PTHS). This collaborative study combines Dr. Philpot’s expertise in autism and neuroscience with Dr. Gray’s expertise in translational gene therapy for neurological disorders. The project will follow a platform gene transfer approach using AAV vectors taken by Dr. Gray to initiate a human Phase I trial for Giant Axonal Neuropathy. The approach uses an engineered virus, AAV, to carry a functional copy of the gene disrupted in PTHS into the body and distribute it across the nervous system. In this fashion, a single dose of this gene therapy could permanently restore the gene to cells across the nervous system, treating the disease at its source. This initial pilot study is meant to assess the potential of this as a treatment approach for PTHS, and identify any roadblocks that may exist.

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Pitt Hopkins Research Foundation appoints new board members, 12/5/16

FOR IMMEDIATE RELEASE

Media contact: Jessica Fletcher, Director of Communications, information@pitthopkins.org

Pitt Hopkins Research Foundation appoints new board members;
recognizing a continued commitment to fundraising and research

Los Angeles, Calif. (December 5, 2016) – Effective January 1, 2017, the Pitt Hopkins Research Foundation (PHRF) is proud to announce the appointment of three newly-elected advocates of the Pitt Hopkins Syndrome community to serve on the Foundation’s Board of Directors: Nicole Almond Anderson, MNLM (Phoenix, Ariz.); Corinne DePersis, Ph.D. (Denver, Colo.) and Will Eyres (New Brunswick, Canada).

The mission of the Pitt Hopkins Research Foundation is to support research dedicated to finding a treatment, and an eventual cure of Pitt Hopkins syndrome and other similar disorders. The PHRF is served by two boards; the Board of Directors, comprised of parents and professionals who volunteer their time, so that nearly 100% of all funds donated go to finding a cure, and the Scientific Advisory Board. Together, these individuals promote awareness of Pitt Hopkins Syndrome, dedicate their time to advancing research andbringing practical treatment into current medical practice, as well as support families of children and adults with Pitt Hopkins Syndrome.

“Each one of these individuals shown an incredible dedication to helping not only their own kids, but all kids with Pitt Hopkins and we feel incredibly lucky to have them join the team,” said Audrey Davidow, President of the Board of Directors for the Pitt Hopkins Research Foundation.

Anderson, DePersis and Eyres join current board officers and general members: Audrey Davidow Lapidus, President, Theresa Pauca, Vice President; Heather Maginn, Secretary; Diane Sellew, Treasurer; Jessica Fletcher, Director of Communications; Eric Lapidus, Director of Fundraising; Paul Pauca; Jack Maginn; Jeff Davidow; Diane Krell; Traci Green and Claudette Mirigliani.

Learn more about the newest board members below.

Nicole Almond Anderson, Mother to Alexandra, 22 mos. old

“Seven months ago Alexandra was diagnosed with Pitt Hopkins Syndrome and in an instant the dreams I had envisioned for her were crushed. As much as I grieved this news, I also vowed to never stop fighting for a better life for our daughter,” said Nicole Almond Anderson. “Just hours after getting the call from the neurologist, I found the Pitt Hopkins Research Foundation and was immediately welcomed into their courageous community by their president, Audrey. I remember telling her that night how ready I was to start fundraising for a cure. From that conversation (and from an immense fire burning within me), we launched Alexandra’s Pitt Crew to garner support from friends and family. Only 90 days after publicly announcing the news and beginning our fundraising campaign, we now have 175 active donors that have given nearly $20,000 to fund a cure. We are so incredibly grateful for their support,” she added.

Anderson believes her experience, education and dedication has equipped her with the essential skills needed to be a change-agent for her daughter and the greater Pitt Hopkins community. For nearly a decade, Anderson’s career at Arizona State University (ASU) has provided her with experience in nonprofit event planning, donor engagement and marketing and communications. Currently, she is the Manager of Marketing, Communications and Stakeholder Relations for the ASU Lodestar Center for Philanthropy and Nonprofit Innovation. Before coming to ASU, she was at the Health Industry Business Communications Council, a nonprofit that helps to ensure safe and efficient healthcare delivery via electronic communication devices. Anderson received a BA in Journalism and Mass Communication from the Walter Cronkite School of Journalism and Mass Communication at ASU, as well as Masters of Nonprofit Leadership and Management from the College of Public Service & Community Solutions at ASU. She also serves as President of the Sun Devil Club’s Young Professionals Group and previously she was the Vice President of the ASU Young Alumni Chapter, a member of the Young Nonprofit Professionals Network and a Class 36 member of Valley Leadership. She now looks forward to combining her passion to serve, along with advocating for those that are developmentally disabled, by getting involved in local pediatric disease advocacy groups.

“As devastating as getting the diagnosis was, we also were filled with hope after reading about the incredible research already being funded by the PHRF. I am beyond humbled and honored to join their board and I can say with certainty that Alexandra’s incredible Pitt Crew and her family and I look forward to making a positive impact on the organization and helping to continue this critical work,” she concluded.

Corinne DePersis, Mother to Madeleine, 2 years old

“When we received the call that Madeleine had been diagnosed with Pitt Hopkins Syndrome, my world shattered. We had been fighting for months and months to help Maddie ‘catch back up’ to the developmental milestones that kept passing us by. For a fleeting moment, the diagnosis felt like all that fighting was for naught, and her diagnosis predetermined her fate. But that night, with swollen, tear-filled eyes, I found the Pitt Hopkins Research Foundation and the members who had picked up the fight against this devastating genetic condition,” said Corinne DePersis, Ph.D. “Every parent wants to do everything they can for their children, to provide every opportunity to succeed which is why I felt so strongly about becoming a member of this board. I am dedicated to expanding the breadth and depth of research to help discover treatments and ultimately a cure for Pitt Hopkins Syndrome. I am so grateful for the relationships with the scientific community the foundation has already cultivated and I look forward to enriching these relationships,” she added.

DePersis’ background has also uniquely prepared her for the Pitt Hopkins Research Foundation board of directors. She received her Bachelors of Science degree in Biology from the State University of New York College at Geneseo. After which she received a Cancer Research Training Award for a year of research at the National Cancer Institute at the National Institutes of Health main campus in Bethesda, Md. DePersis then continued her scientific career by accepting a graduate student position at the University of Colorado Health Sciences Campus in Denver, Colo. where she studied Immunology, culminating in her Doctoral degree. When her daughter, Madeleine, started showing concerning symptoms, DePersis left her professional life to be a full-time Mom and manager of Madeleine’s health and therapy regimen.

“My formal scientific training provides me with the keen understanding of the challenges we face in research. I also understand the enormity of the financial burden required to fund research projects we need to advance the science towards a real breakthrough,” said Corinne DePersis, Ph.D. She has shown a strong commitment to fundraising and has hosted several successful fundraisers including ‘Madeleine’s 2nd Birthday Party’ which raised over $5,000 and the ‘Pitt Hopkins Awareness Day event’ in Denver which yielded several thousand more. “It is time to explore more substantial funding sources and I look forward to new opportunities doing such as part of the board,” she added.

Will Eyres, Father to Iris

“I am honored to be part of the Pitt Hopkins Research Foundation, an amazing organization that has accomplished so much in its short history, and look forward to contributing to the ultimate goal of finding a cure for all our kids,” said Will Eyres.

Eyres has worked around the world in the maritime industry for ten years and currently he and his family reside in New Brunswick, Canada. “Fundraising is one of the best things we can do for our kids and we are very fortunate to have the full support of our entire family,” he added.

“‘Rafa’s for Research’ has been a great event and we hope to make it better every year and find additional avenues of fundraising in the near future,” he added. Rafa’s Cafe raised an astounding $32,000 for research on November 5, 2016, during the Dallas Family Conference. Additional thanks to Raphael and Kathy Carreon, owners of Rafa’s, and the grandparents of Iris Eyres, who was diagnosed with PTHS last year.

For additional information regarding the Pitt Hopkins Research Foundation, visit https://pitthopkins.org. If you have questions, please email information@pitthopkins.org.

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ABOUT THE PITT HOPKINS RESEARCH FOUNDATION

Established in 2013 as a 501(c)3, the Pitt Hopkins Research Foundation (PHRF) exists to support critical research dedicated to finding a treatment, and an eventual cure of Pitt Hopkins syndrome and other similar disorders. Pitt Hopkins Syndrome (PTHS) is a rare, neuro-developmental disorder caused by a mutation/deletion of the TCF4 gene on the 18th chromosome. It is characterized by significant developmental delays, problems with motor coordination, breathing abnormalities and seizures. Most individuals with Pitt Hopkins do not develop functional speech. Pitt Hopkins affects all races and both genders equally. Since the gene that causes Pitt Hopkins was only found in 2007, currently there are approximately 650+ people in the world diagnosed with this incredibly rare syndrome. The Pitt Hopkins Research Foundation is dedicated to supporting the Pitt Hopkins community with resource recommendations, scientific symposiums and family conferences, parental support and the latest medical information. For more information, please visit: https://pitthopkins.org.

PDF File:  new-board-members_press-release_phrf_dec-2016_final

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Madeleine’s Endless Sunshine

Madeleine Amelia DePersis Zarlengo has not only a big name, but a big burden to carry. She has Pitt Hopkins Syndrome. Despite her diagnosis, she is so light, effortless in her ability to bring joy to all and a provider of endless sunshine. It seemed only fitting that in honor of her second birthday, August 3, she have a “Sunshine” themed party to raise awareness and funds for the Pitt Hopkins Research Foundation.

Threat of rain didn’t scare away guests who were all rewarded with perfect weather just as the party began. One hundred of her closest friends and relatives joined together in her backyard to celebrate all of her accomplishments over the past two years. Madeleine had a lot to celebrate! She had just become independently mobile as an official “crawler.” Standing was rapidly becoming a favorite pass time and attending school was a whole new adventure just starting.

Guests enjoyed the afternoon sipping on “Liquid Sunshine” (a pineapple and tequila cocktail) and sparkling pink lemonade. No one went hungry either with plenty of Madeleine’s Dad’s famous smoked pulled pork, Madeleine’s Grandmother’s inspired Mac ‘n Cheese and Madeleine’s favorite smokey bacon baked beans. Dessert satisfied everyone’s sweet tooth with many options including pink-chocolate dipped rice crispy treat pops, Madeleine’s Mom’s signature pineapple upside-down mini cupcakes and a two-tier strawberry lemonade birthday cake.

Never a dull moment, there was lots to do besides just eat! Thomas and Paker, Maddie’s friends and brothers to Henry, another little boy with Pitt Hopkins Syndrome, performed street magic and created balloon animals. Friends enjoyed splashing around in the water table and cooling down in the wading pool. The biggest hit, and possibly the most simple, were the endless supply of bubbles from the bubble machine that filled the yard with delight.

In lieu of gifts, Madeleine’s Mom and Dad requested donations be made to the Pitt Hopkins Research Foundation. There could be no better gift than a contribution to the scientific research seeking treatments and a cure for the rare syndrome that affects Maddie every minute of every day. Almost $5000 was collected in Madeleine’s honor that afternoon.

 

To say thanks, every child received a personalized gift bag with sunglasses and other goodies and every guest was sent home with sunshine shortbread cookies. But the smile on Madeleine’s face when she smashed her cake and then splashed in the pool was all anyone at that party needed to know how grateful she was for their support.

Madeline’s family has gone onto raise another 3K for Pitt Hopkins Awareness Day on September 18th, 2016, in honor of their sweet sunshine.  

 

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Press Release, 4th Annual Pitt Hopkins Syndrome Day 9/18/16

FOR IMMEDIATE RELEASE
PITT HOPKINS:

The Pitt Hopkins Research Foundation celebrates its fourth International Pitt Hopkins Syndrome (PTHS) Day to Raise Awareness and Funding for Pitt Hopkins Research

Los Angeles, California September 6, 2016 –The Pitt Hopkins Research Foundation (PHRF) is proud to announce the celebration of its fourth annual International Day of Recognition for Pitt Hopkins Syndrome, a rare neurodevelopmental disorder caused by a spontaneous mutation on the 18th chromosome.

To bring further awareness to the 18th chromosome, we have chosen the 18th of September as our annual awareness day. Families and friends around the globe will celebrate children affected by Pitt Hopkins Syndrome and begin to expand recognition for the disorder and help raise awareness and funding for research towards a cure.

GOALS FOR AWARENESS DAY

On Sept. 18th, as we celebrate our children and all they have achieved we want to take the opportunity to introduce more people to the beauty and trials of living with Pitt Hopkins.

  • We want to promote our reasons for research, our belief and dedication to finding a cure (see below) and encourage people to donate to our foundation.
  • We want medical professionals, in particular pediatricians, to learn more about the symptoms and features (see below) so that they can refer their patients for genetic testing in a timely manner.
  • We want families with undiagnosed, developmentally delayed children to perhaps see in the faces of our children, something familiar. We want them to know there is new testing available–Whole Exome Sequencing –that just might be able to help them find the answers they’ve been searching for.
  • We want other professionals that work with children and their families with special needs, eg kindergarten teachers, special needs teachers, OTs , physiotherapists to know the symptoms and features.
  • We want any families who have been diagnosed to find our support group at www.pitthopkins.org and join us!

WHAT IS PITT HOPKINS SYNDROME?

Pitt Hopkins is a severe neurological disorder caused by loss of function of the TCF4 transcription factor located on chromosome 18. PTHS is characterized by developmental delays, breathing problems of episodic hyperventilation and/or breath-holding while awake (55%-60%), recurrent seizures/epilepsy (40%-50%), gastrointestinal issues, and distinctive facial features. Most do not develop speech. Not all of these symptoms need to be present to warrant genetic testing.

PTHS was first described by D. Pitt and I. Hopkins in the Australian Pediatric Journal in 1978. The connection to TCF4 was not established until 2007 when it was found to play an essential role in the development of the nervous system and the brain. Any functional deficiency of TCF4 greatly affects how a child develops over time.

Currently about 650 people have been diagnosed with Pitt Hopkins. However, given the recent discovery of the gene in 2007, there are likely many more out there who remain undiagnosed. Overall prevalence of PTHS is unknown. However, one laboratory estimated that the frequency of chromosome 18q21 deletions associated with PTHS is between 1 in 34,000 and 1 in 41,000. An estimate from another researcher is 1 in 200,000-300,000. Researchers will need to recognize individuals with PTHS in all age groups first and molecular analyses should be more widely available too, before this estimate is more accurate. PTHS occurs in both males and females and is not limited to a specific ethnic background.

WHY WE BELIEVE IN A CURE

In the past, genetic syndromes like Pitt Hopkins and Down Syndrome, for instance, were thought to be incurable. But that tide is turning. In 2010, Tom Insel, Director of the National Institute for Mental Health said, “Just three years ago, I would have said that [intellectual disability] is a disability needing rehab, not a disorder needing medication. But it’s all changing.”

Right now, there are clinical trials for similar neurodevelopmental disorders like Rett Syndrome and Angelman Syndrome using compounds that have reversed the syndromes in mice. This has just happened in the last five years, and gives us a great deal of hope that a reversal, or at least amelioration of Pitt Hopkins symptoms, could be possible in humans, too.

We started The Pitt Hopkins Research Foundation with the singular goal of reversing Pitt Hopkins in people. In the last four years we have funded nearly $2,000,000 in research grants. Scientists at University of Alabama and University of North Carolina have created Pitt Hopkins Mouse models and neuronal stems cells and are testing them to see what drugs may help ameliorate symptoms. And this year, scientists discovered not one, but two therapeutics that have reversed the symptoms of Pitt Hopkins in the mice. We hope to bring these drugs to trial in 2017.

Although there are only 650 diagnosed, this research has far reaching effects into the science of memory and learning. Because we already KNOW the gene that causes PTHS- TCF4, we are in an important place to fund meaningful research, research that could possibly give insight to other learning, memory and motor disorders with no known cause like Alzheimers, Autism, Epilepsy and Parkinsons.

ABOUT THE PITT HOPKINS RESEARCH FOUNDATION

The Pitt Hopkins Research Foundation is an all-volunteer organization of families and professionals dedicated to finding a cure for Pitt Hopkins through the funding of an aggressive research agenda, education, and advocacy. Our goal is to bring practical treatment into current medical practice as quickly as possible. In just four years the PHRF will have raised and distributed nearly $2,000,000 in grants and fellowships.

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Gene Therapy Grant Awarded, Drs. Steve Gray & Ben Philpot, UNC-CH

Gene therapy success stories are not only a hope but now becoming a reality. We won’t let Pitt Hopkins fall behind in this exciting and promising research. In August of 2016 the Pitt Hopkins Research Foundation awarded its first gene therapy grant, to Dr. Steve Gray at UNC and one of our pioneer heroes and researchers Dr. Ben Philpot. Here’s to Pitt Hopkins heroes old and new… And to the promise of gene therapy!

Grant summary

The laboratories of Dr. Ben Philpot and Dr. Steven Gray at the University of North Carolina at Chapel Hill are collaborating on a project to investigate the feasibility of a gene therapy approach for Pitt-Hopkins syndrome (PTHS). This collaborative study combines Dr. Philpot’s expertise in autism and neuroscience with Dr. Gray’s expertise in translational gene therapy for neurological disorders. The project will follow a platform gene transfer approach using AAV vectors taken by Dr. Gray to initiate a human Phase I trial for Giant Axonal Neuropathy. The approach uses an engineered virus, AAV, to carry a functional copy of the gene disrupted in PTHS into the body and distribute it across the nervous system. In this fashion, a single dose of this gene therapy could permanently restore the gene to cells across the nervous system, treating the disease at its source. This initial pilot study is meant to assess the potential of this as a treatment approach for PTHS, and identify any roadblocks that may exist.

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Alexandra’s Pitt Crew

Every parent that has been on the receiving end of a diagnosis can relate to this. Alexandra is a sweet, beautiful 18 month old little girl who was recently diagnosed with Pitt Hopkins syndrome. Her mom and dad put together this beautiful video capturing their journey. Please take a few minutes to watch. Thank you Nicole and Matt Anderson, for putting into words what so many of us have felt in that moment of diagnosis and the worry of the unknown future for our kids. We are all in this together.

To follow along Alexandra’s journey, visit alexandraspittcrew.org and on Facebook at Alexandra’s Pitt Crew.

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HDACi meds may reverse effects of Pitt Hopkins, Drs. Kennedy & Sweatt

Dr. Andrew Kennedy and Dr. David Sweatt publish findings that show HDACi meds may reverse effects of Pitt Hopkins

The very first grant the Pitt Hopkins Research Foundation made back in 2012 was to the lab of Dr. David Sweatt at the University of Alabama Birmingham. He needed the money to hire the most promising young researcher he could find to devote his career to Pitt Hopkins. He found that in Dr. Andrew Kennedy. They are both scientists with hearts as big as their brains, and the more we learn about science, the more we know how incredibly lucky we are to have them both in our court. Dr. Kennedy just started his career as a professor at Bates College in Maine. Dr. Sweatt is now the chair of the pharmacology Department at Vanderbilt University. This paper is the culmination of their incredible work at UAB… and shows a very promising treatment for Pitt Hopkins. So what does that mean? It means there is an already FDA approved medicine reversing the symptoms of Pitt Hopkins in mice. It means there is increasing evidence we will be able to reverse symptoms in our children. It means we are actively pursing clinical trials. And it means, more than anything, that we will continue to fight for every little miracle.

Thank you Drs. Kennedy, Sweatt and UAB for doing this amazing work… and to all those who supported it, we cannot EVER thank you enough!

Read full article here:  http://www.cell.com/cell…/fulltext/S2211-1247(16)31036-1

 

Study suggests new way to treat rare autism disorder

by Bill Synder | Thursday, Aug. 25, 2016, 11:01 AM

A protein that plays a powerful role in learning and memory may be a key to improving treatment of a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), a new study suggests.

J. David Sweatt, Ph.D., the new chair of the Department of Pharmacology in the Vanderbilt University School of Medicine, has been studying the protein, called transcription factor 4 or Tcf4, for several years.

In a paper published this week by the journal Cell Reports, Sweatt and his colleagues at the University of Alabama at Birmingham (UAB) report that mice deficient in Tcf4 exhibit impairments in social interaction, vocalization, learning and memory characteristic of PTHS.

The impairments were “normalized” when the mice were given small-molecule drugs called HDAC inhibitors, which alter Tcf4-associated gene expression in the brain. The finding suggests that “broadly acting, epigenetically targeted therapeutics … might be particularly beneficial in PTHS patients,” the researchers concluded.

“We are quite excited by these findings, said Sweatt, a Vanderbilt University-trained pharmacologist who formerly chaired the Department of Neurobiology and directed the McKnight Brain Institute, both at UAB.

“Pitt-Hopkins Syndrome is an orphan disease that has not been extensively studied,” he said. “Having identified one potential avenue for possible therapeutics is an important step forward.”

Epigenetics refers to environmental factors that affect DNA transcription, the read-out of the genetic code, and thus gene expression. For example, histone deacetylase (HDAC) enzymes help regulate the way DNA is packaged and transcribed in part through acetylation, by adding acetyl groups to the histone proteins that coordinate gene structure.

Transcription factors like Tcf4 adjust the transmission of signals across the synapses, or gaps between nerve cells, a phenomenon known as synaptic plasticity. A type of synaptic plasticity called long-term potentiation, or LTP, is associated with the brain’s ability to learn, acquire language and lay down memory.

It’s been known for some time that Tcf4 exerts its effects on transcription by attracting HDACs. Drugs called HDAC inhibitors have been long used in psychiatry and neurology to stabilize mood and prevent epileptic seizures. More recently they have been studied as possible treatments for cancer, Alzheimer’s disease and depression.

Through their mouse model, Sweatt and his colleagues connected the observed effects of Tcf4 and HDACs on gene expression in the brain. Their study adds credence to the notion that chemical modification of DNA and DNA packaging can result in to long-lasting behavioral change, even post-developmentally.

Future studies are planned to further investigate the possible use of currently available FDA-approved HDAC inhibitors in the Pitt-Hopkins mouse model, Sweatt said.

The study was supported by the Defense Advanced Research Projects Agency (DARPA), the National Institutes of Health (grants MH57014 and MH104158), Civitan International, the Simons Foundation, McKnight Brain Research Foundation and the Pitt-Hopkins Research Foundation.

http://news.vanderbilt.edu/2016/08/study-suggests-new-way-to-treat-rare-autism-disorder/

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