A New Study Finds That Gene Therapy May Prevent or Reverse Pitt-Hopkins Syndrome

In normal development, genes are usually inherited in pairs – with one copy from the father and one inherited from the mother. When one copy of the TCF4 gene, which is located on chromosome 18q 21.2, is mutated or absent the result leads to Pitt-Hopkins syndrome and a deficiency in the TCF4 protein. The deletion typically occurs in the egg or sperm just before conception or in the early embryonic stages following conception.

According to a recent article in SciTech Daily, Pitt-Hopkins was identified in 1978 by Australian researchers. There are estimates of about five hundred cases in the world, yet other estimates have been as high as 10,000 or more in the United States.

People who have Pitt-Hopkins, a neurodevelopmental disorder, have been misdiagnosed as having Autism or ‘atypical’ (abnormal) autistic characteristics.

Symptoms may include:

  • Difficulty speaking
  • Developmental delay
  • Episodic hyperventilation
  • Epilepsy or recurrent seizures
  • Gastrointestinal (GI) difficulties
  • Unique facial features

Note that these symptoms are also symptoms of autism spectrum disorder.

Young Pitt-Hopkins patients may appear to be smiling or laughing frequently. The disorder is not limited to a specific ethnic group, and it is found to affect both males and females.

About the Research

The research was conducted at North Carolina University in the neuroscience lab of Dr. Ben Philpot. The team developed a gene-therapy technique that restored the gene deficiency in Pitt-Hopkins patients. The study found that restoring gene activity in animal models of Pitt-Hopkins can prevent various symptoms of the disease.

Is Postnatal Gene Therapy the Key?

Researchers at NCU demonstrated that postnatal gene therapy is capable of reversing or preventing many harmful effects of Pitt-Hopkins. The medication used in the study prevented memory impairment, anxiety, and abnormalities in gene expression in the brain cells of newborn mice.

Dr. Philpot emphasized that currently there is no treatment for Pitt-Hopkins. He stated further that consideration should be given to the importance of restoring the Pitt-Hopkins gene to normal levels as a viable treatment option for the disorder.

About TCF4

TGF4 is known as a “transcription factor” gene, similar to a master switch controlling hundreds of genes. Disruption of TCF4 causes developmental abnormalities. Restoring TCF4 appears to be the highest and best use to treat Pitt-Hopkins syndrome. Note, however, that the treatment has not been tested.

Dr. Philpot and his associates then created a Pitt-Hopkins mouse model which exhibited typical symptoms of Pitt-Hopkins. But when the team restored the TCF4 gene to a normal level, starting from embryonic life, symptoms did not appear.

The studies provide evidence of restoring gene activity in every type of neuron in order to prevent Pitt-Hopkins symptoms.

State of the Art

The team then created an experiment that was modeled on state-of-the-art gene therapy. About fifty percent of TCF4 expression was turned off in engineered mice. It went like this:

A virus enzyme was delivered to the neurons. It was used to reset the expression at birth. The researchers analyzed the brains of the mice during the next few weeks. The mice that received treatment were noticeably smaller with smaller brains when compared to the untreated mice. However, that group did not exhibit the abnormal behavior observed in the Pitt-Hopkins mice that were untreated.

Dr. Philpot and the team plan to further investigate the efficacy of their novel strategy in mouse models.

In addition, the team is planning a gene therapy that utilizes the human TCF4 gene for the eventual testing of children with the disorder.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

Follow us