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10 HEALTH AND LABORATORY MAGAZINE

A POTENTIAL CURE FOR AUTISM:

GENE THERAPY COULD TREAT

PITT-HOPKINS SYNDROME

A new study has shown that gene
therapy may be able to prevent or

reverse many deleterious effects of

Pitt-Hopkins syndrome.

New research from the 34.000 and 1 in 41.000. The scientists, who pub- the father. Pitt-Hopkins – but it hasn’t yet been
UNC Neuroscience Center The disorder affects both lished their findings in the syndrome arises in a child tested.
lab of Ben Philpot, Ph.D., men and women and is not journal eLife, created an when one copy of the gene
finds restoring lost gene restricted to a single ethnic experimental, gene-ther- TCF4 is missing or mutat- Philpot’s team, led by first
activity prevents many group. apy-like technique to ed, resulting in an insuffi- author Hyojin (Sally) Kim,
disease signs in an animal restore the normal function cient level of TCF4 protein. Ph.D., a graduate student
model of Pitt-Hopkins syn- Pitt Hopkins syndrome is of the gene-deficient in Typically, this deletion or in the Philpot lab during
drome, a rare, single-gene classified as an Autism people with Pitt-Hopkins mutation occurs spontane- the study, developed a
neurodevelopmental Spectrum Disorder, and syndrome. The medication ously in the parental egg or mouse model of Pitt-Hop-
condition. some people who have it prevented the onset of sperm cell prior to con- kins syndrome in which the
have been diagnosed with disease indicators such ception, or in the earliest level of the mouse version
Pitt-Hopkins syndrome is Autism, ‘atypical’ autistic as anxiety-like behavior, stages of embryonic life of TCF4 could be reliably
a rare genetic condition characteristics, and/or memory impairments, and following conception. halved. This mouse model
caused by a mutation in Sensory Integration Dys- abnormal gene expression showed many typical signs
the TCF4 gene on chro- function. Many researchers patterns in afflicted brain Only about 500 cases of of the disorder. Restoring
mosome 18. Pitt-Hopkins believe that treating Pitt cells in newborn mice that the syndrome have been the full activity of the gene
syndrome is characterized Hopkins syndrome will lead would otherwise model the reported worldwide since it from the start of embryon-
by developmental de- to treatments for similar syndrome. was first described by Aus- ic life fully prevented these
lay, potential respiratory disorders because of its tralian researchers in 1978. signs. The researchers also
concerns such as episodic genetic link to autism and “This first, proof-of-prin- But no one knows the syn- found evidence in these
hyperventilation and/ other conditions. ciple demonstration sug- drome’s true prevalence; initial experiments that
or breath-holding while gests that restoring normal some estimates suggest gene activity needed to
awake, recurrent seizures/ For the first time, research- levels of the Pitt-Hopkins that there could be more be restored in essentially
epilepsy, gastrointesti- ers at the University of syndrome gene is a viable than 10.000 cases in the all types of neurons to
nal difficulties, a lack of North Carolina School of therapy for Pitt-Hopkins United States alone. prevent the emergence of
speech, and distinctive Medicine have shown that syndrome, which otherwise Pitt-Hopkins signs.
facial features. Children postnatal gene therapy has no specific treatment,” Since TCF4 is a “tran-
diagnosed with Pitt-Hop- may be able to prevent or said senior author Ben scription factor” gene, a Next, the researchers set
kins syndrome often have reverse many of the nega- Philpot, Ph.D., Kenan Dis- master switch that controls up a proof-of-concept
a happy and lively attitude tive effects of Pitt-Hopkins tinguished Professor of Cell the activities of at least experiment modeling a
with frequent smiling and syndrome, a rare genetic Biology and Physiology at hundreds of other genes, real-world gene therapy
laughing. disorder. Severe develop- the UNC School of Medi- its disruption from the start strategy. In engineered
mental delay, intellectual cine and associate director of development leads to mice in which roughly
The prevalence of disability, respiratory and of the University of North numerous developmental half the expression of the
Pitt-Hopkins syndrome movement abnormali- Carolina (UNC) Neurosci- abnormalities. In principle, mouse version of Tcf4 was
in the general popula- ties, anxiety, epilepsy, and ence Center. preventing those ab- switched off, the research-
tion is unclear. However, moderate but distinctive normalities by restoring ers used a virus-delivered
some estimates place the facial abnormalities are all Most genes are inherited normal TCF4 expression enzyme to switch the
frequency of Pitt-Hopkins symptoms of this autism in pairs, one copy from as early as possible is the missing expression back
syndrome between 1 in spectrum disorder. the mother and one from best treatment strategy on again in neurons, just