Hope for A Cure: A Gene-Therapy Approach for Pitt-Hopkins Syndrome

By Yue Yan

Image by Marta D. [CC-BY-4.0]

Fror most people, reciting the ABC’s and 123’s is a neurodevelopmental disorder. It is caused by a mutavery simple task. For most people, their faces are tion in the chromosome 18 gene Tcf4, which creates just an average of their parents’ faces and noth- a protein when expressed. Symptoms of this disorder ing more. However, many men, women, and children include epilepsy, trouble breathing, developmental in the world find learning even the simplest of con- delay, digestive issues, impaired speech, and distinccepts to be a challenge. For many men, women, and tive facial features (Figure 1). Since Pitt-Hopkins Synchildren, their entire lives were changed the moment drome is rare, it is not well-understood, so researchers they were born. These individuals all have one thing like Sally Kim are working hard to better understand in common: Pitt-Hopkins Syndrome, a form of autism it. that causes breathing problems, epilepsy, developmental/intellectual delays, and facial deformities. It can lead to social isolation and, in extreme cases, can even be fatal. Consequently, many researchers around the world are trying to understand this condition better to possibly treat or even cure it. One such researcher is Sally Kim. Sally Kim is a Ph.D. student working in Dr. Ben Philpot’s lab at UNCChapel Hill. Under Dr. Philpot, her study focuses on developing a gene Figure 1. A photo of the facial features caused by Pitt-therapy approach for Hopkins Syndrome. Image courtesy of Wikimedia. Pitt-Hopkins Syndrome. Pitt-Hopkins Syndrome To start, the researchers first identified which is an extremely rare but cells expressed the protein. By doing so, they would

Sally Kim, Ph.D student very serious genetic and be able to locate in which cells Pitt-Hopkins Syn22

Carolina Scientific medicine & health drome patients are missing the fully-functional gene. rus particle...think of this virus as a delivery truck… They also wanted to determine when Pitt-Hopkins and then we’re going to add a genetic material into Syndrome should be treated: the disease changes as the truck and then we’re going to put this entire virus affected individuals grow older. into the human system.”1 By researching which cells The researchers discovered all of this informa- and parts of the brain express these genes, Sally Kim tion by developing a green fluorescent protein re- hopes to be able to develop a virus that only targets porter mouse. The green fluorescent protein only places where the protein is needed. She goes on to glows if the gene of interest (in this case, Tcf4) is also mention that because Pitt-Hopkins “develops early expressed, to better see which cells were expressing in life...we don’t know whether all the phenotypes the Tcf4 gene. They then used this protein reporter on (symptoms) can be treated.”1 Due to this uncertainty, the brains of mice of varying ages to see where in the and the fact that Pitt-Hopkins is a rare and understudbrain Tcf4 is expressed. ied disorder, Kim predicts that it will take about 5-10 As a result, Sally Kim and the other researchers years before a treatment can be developed. Working found out that protein expression was prominent in under Dr. Philpot, Sally Kim has discovered which cells the parts of the brain that focus on processing the are affected by the mutated Tcf4 gene in individuals senses and memory. They also discovered that the with Pitt-Hopkins Syndrome through the use of mice. non-electrical cells focused on maintaining and sup- Their research has the potential to develop a gene porting the nervous system also have prominent lev- therapy treatment that targets the correct cells and els of the protein. However, their research is still on- discover exactly when doctors should treat patients going. Sally Kim and her colleagues plan on using a with the disorder. By using these findings, Sally Kim group of mice with a Tcf4 mutation, causing lowered hopes to contribute to developing a treatment soon levels of the protein, and then bringing the protein to to ease the worries of the parents of those affected. normal levels at different ages. Afterwards, they will With this hope, Sally Kim and the many others perform a behavioral assessment to see how effec- researching Pitt-Hopkins continue to do their part to tive the treatment was at different ages to determine try and give those affected a normal life. They hope when it is best to treat Pitt-Hopkins Syndrome. that one day, their parents can finally rest easily, Sally Kim hopes to use this information to de- knowing that their child’s life is no longer in constant velop a treatment for Pitt-Hopkins with gene therapy danger. They dream that those kids can grow up and (Figure 2). She describes gene therapy as “using a vi- fulfill their goals, just like everyone else. Perhaps one day, their hopes and dreams can come true. Although, there is still a long way to go before they can without a doubt save the lives of the many men, women, and children that have been affected by Pitt-Hopkins Syndrome.

References

1. Interview with Sally Kim. 09/15/20