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.
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.
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.
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.
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.
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 firstname.lastname@example.org if you are interested in starting the donation process.
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. Metabalomics profiling
Numerous families participated this year in the metabalomics profiling study out of Baylor University. In addition to giving families increased information about their child’s personal metabolic profile, the study, conducted by Dr. Sarah Elsea and Dr. Joseph Alaimo, revealed specific areas of metabolism and mitochondrial deficiencies which will be further pursued in 2017.
This study is ongoing. If you’d like to participate please contact Dr. Joseph Alaimo, email@example.com.
12. 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.