|NEWSRoom | Source: University of Alabama at Birmingham|
Gift Enables UAB to Advance Research Efforts in Rare Pitt-Hopkins Syndrome
The greatest fear of many parents is that the health of their infant child might somehow be compromised. You always watch for those little milestones—the lifting of the head, the responding to sound, laughing, reaching for objects, grasping toys, recognition of voices.
When their then 6-month-old son Calvin started missing some of those common milestones last year, Audrey Davidow Lapidus and her husband Eric knew something wasn’t quite right.
Little Calvin was not sitting on his own. He didn’t roll, either—both milestones typically achieved by that age. The Lapiduses voiced their concerns to their Los Angeles doctors, and when their baby reached 8 months old, the physicians agreed that tests needed to be performed.
A five-month medical odyssey ensued, complete with an MRI and various genetic tests. Finally, a whole exome sequencing test revealed that Calvin had Pitt-Hopkins syndrome (PTHS), a disorder characterized by intellectual disability and developmental delays, which can range from moderate to severe. Breathing problems, recurrent seizures and distinctive facial features also are hallmarks of PTHS.
Audrey Lapidus immediately began a search for answers in an effort to give Calvin an opportunity to live the best life possible. Her pursuit recently led to UAB and the lab of David Sweatt, PhD, professor and chair of the Department of Neurobiology, and resulted in a $85,000 gift to Sweatt’s lab to advance research efforts in PTHS—a syndrome that is believed to have been diagnosed in fewer than 200 children worldwide.
As a result, Sweatt will become the first molecular neurobiologist in the United States investigating this disorder.
“Ethical and social imperative”
“I believe there is an ethical and social imperative for someone in the US basic neuroscience community to begin to investigate the molecular neurobiology of PTHS, and lay a cornerstone of research that will allow the hope of the development of a treatment for these patients in the future,” Sweatt says.
The Lapiduses clearly aren’t the type of people to sit back and wait for answers. They have been proactive from the start, and their journey from Calvin’s diagnosis to funding a gift to Sweatt’s lab took all of three months.
Of course there was a detour along the way. Early on, some doctors speculated Calvin had Angelman syndrome, a neuro-genetic disorder often misdiagnosed as cerebral palsy or autism. Audrey began looking into Angelman’s research and eventually stumbled across Sweatt’s biography online.
Audrey e-mailed Sweatt on a whim when the PTHS diagnosis of Calvin was confirmed even though the family had not raised a penny at that point. “I figured he wouldn’t respond,” Audrey says, “but he responded promptly with the kindest, most encouraging response we could have imagined. When many others were telling us it couldn’t be done, he wrote to me and said informed and proactive parents can be a very powerful force in helping propel scientific discovery in the area of rare diseases.”
The Lapiduses immediately started fundraising efforts after Calvin’s diagnosis was official. They launched an e-mail and Facebook campaign with the help of loved ones and raised $200,000 in just six weeks. “Our family and friends were amazing,” Audrey says. “People just came out of the woodwork to make donations.” Corporations like Bimbo Bread and Jose Cuervo also offered financial gifts.
Audrey and Sweatt continued to e-mail each other, with Sweatt submitting proposals for research projects to her.
In addition to this, the Lapiduses began meeting other families around the country who had children with PTHS. They became close with Paul and Theresa Pauca of North Carolina, whose 7-year-old son Victor has PTHS. The Paucas along with a number of other families already had established a fund of $30,000, raised in the past three years through 5K walks.
The Lapiduses ultimately decided to join forces with these families, who were all members of the Pitt Hopkins Foundation. After coming on board, the Lapiduses helped form a scientific review board for the foundation. The group voted to grant the $85,000 gift to Sweatt’s lab earlier this month at the suggestion of Princeton University Professor Rebecca Burdine, PhD, the acting head of the group’s scientific review board.
“I have learned a lot about Dr. Sweatt through all of this,” Audrey says. “It is clear he is an esteemed, world-class researcher, but he is also a very kind and decent man. We feel very grateful and excited to have him in our court. He doesn’t know this, but behind his back, I call him our angel genius.”
PTHS genetic cause identified
Two physicians first described Pitt-Hopkins syndrome in 1978. Until recently, the diagnosis of PTHS was based on a person’s medical history and a physical examination. However, new technology has enabled scientists to identify the genetic cause of PTHS, which researchers recently discovered is caused by either a mutation or complete deletion of the TCF4 gene, located on the long arm of chromosome 18. Now, diagnosis can be made with a simple blood test.
Currently, fewer than 200 cases of PTHS are known to exist around the world, and there is a profound lack of information concerning the molecular neurobiology underlying the syndrome, Sweatt says.
“It is imperative to investigate the molecular and cellular basis of nervous system dysfunction in PTHS,” Sweatt says. “We need a treatment for these patients. The identification of the dysfunctional TCF4 transcription factor gene as the genetic basis of the disorder is a critical step forward in beginning to understand the diagnosis, etiology and molecular biology of PTHS.”
The project to be undertaken by the Sweatt laboratory encompasses a set of studies to investigate the cognitive dysfunction associated with PTHS, focusing on mechanistic studies to understand the role of the TCF4 transcription factor in central nervous system function. Animal models and in vitro model systems will be used in the research.
“An ancillary goal of the project is to begin to develop a cadre of basic and clinical researchers who are working on this problem, in order to have at least a minimal critical mass of clinicians and scientists who are knowledgeable in this area,” Sweatt says. “I have never before worked on PTHS, but with the help and confidence manifested by the gift from the Pitt Hopkins Foundation, I am now initiating a PTHS research program in my laboratory in order to begin to undertake this important initiative.
“I feel that as a senior scientist in the field of learning and memory, with a track record of prior discovery related to intellectual disability, I may be able to catalyze scientific and clinical interest in this rare disorder.”
Like any parents, Audrey and Eric have big dreams for 17-month-old Calvin. PTHS doesn’t change that. It’s just that at the moment, their dreams are a bit more focused. They want to be that informed, powerful force of proactive parents Sweatt spoke of that continue to help drive scientific discovery and help their son become the highest-functioning PTHS child he can be.
“My hope for the next decade is that there will be a treatment,” Audrey says. “I always say there is a fine line between hope and too much hope. Of course my wildest hope—the hope that I have to keep in check at the back of my mind and tucked deep in my heart—is that there will be a cure. But my realistic hope is that there will be a treatment within the next decade that won’t necessarily cure our kids, but give them a much higher functioning, fuller life.”
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