New Treatment for Pitt-Hopkins Autism

Researchers as the Lieber Institute for Brain Development (LIBD) have, for the first time, identified a possible treatment for Pitt-Hopkins autism. Pitt-Hopkins syndrome (PHS) is a genetic type of autism, which is characterized by a developmental delay which causes an intellectual deficit, facial dysmorphia, epilepsy, and abnormal breathing among other symptoms. It is quite unknown, which is why talking about it and this new therapy gives hopes to the people and families suffering from PHS.

Causes of Pitt-Hopkins Syndrome

Pitt-Hopkins syndrome is a rare type of genetic illness with an autosomal dominant pattern, which means that we can get the disease or illness with only one copy of the altered gene.

This is caused by a mutation (or complete deletion) of the TCF4 gene. This mutation alters the ability of the TCF4 gene to join with the DNA and control certain genes related to cellular maturation and the processes of cell differentiation and apoptosis (auto-destruction of cells) which is produced during development.

Symptoms of Pitt-Hopkins Syndrome

• Along with the typical symptoms of autism, PHS includes:
• Intellectual disability
• Language and communication problems. Many people with PHS aren’t able to talk, but they can understand and communicate with gestures.
• Happy, but with some behavioral and anxiety problems.
• Epilepsy
• It’s common to have convulsions muscular hypotonia that can lead to difficulty swallowing.
• Repetitive movements
• Ataxia or unsteady gait
• Abnormal breathing. Many people with PHS breathe quickly and hyperventilate, or conversely have apnea.
• They usually have a smaller corpus callosum.
• Vision problems: strabismus and myopia are common.
• Scoliosis
• Gastrointestinal problems. Chronic constipation is most common, but they may also have reflux which causes pain, irritability, and vomit.
• Distinctive physical traits: they are usually shorter than others, microcephaly, undescended testicle.
• Distinctive facial traits: thin eyebrows, sunken eyes, prominent nose, wide mouth and thick lips, thick and cup-shaped ears.

Pitt-Hopkins Syndrome Treatment

Until now, doctors have only been able to treat the symptomatic problems of the patient. In fact, there is no pharmacological treatment to treat the cognitive and behavioral problems in these children.

The good news is that this study has opened new doors to autism treatment. Researchers have found proteins that represent potential therapies for PHS, but that could also help with other types of autism and neuropsychiatric illnesses like schizophrenia. They saw that by modifying these proteins, the abnormalities caused by the PHS gene can be reversed.

What did they do? Until now, other studies centered about the idea of correcting the TCF4 gene, which proved unsuccessful. However, the researchers at the Lieber Institute chose a new approach to understanding the cognitive and behavioral deficits seen in the disease. In genetically modified rats, they identified the anomalies in the brain cell functions that are responsible for these deficits. They found that a protein ion channel (regulates by the TCF4) was too active, which caused a cellular malfunction. When they administered the drugs to block these altered channels, cell function returned to normal.

While this study is in its early stages, it gives new hope to the search for treatments that are effective in treating PHS and other ASD syndromes. The best thing is that the medications that block the channels are already on the market, so moving the results from a lab to a clinic may happen earlier than we thought.