A mice study revealed low doses of romidepsin, an FDA-approved drug used to treat lymphoma, restores the genes associated with social and communication skills.
People on the autism spectrum usually have difficulty establishing and maintaining relationships, however there is currently no treatment for this primary symptoms.
‘We have discovered a small molecule compound that shows a profound and prolonged effect on autism-like social deficits without obvious side effects,’ said Dr Zhen Yan, professor in the department of physiology and biophysics at the University of Buffalo.
For the study, Dr Yan and her colleagues randomly assigned mice to drug and placebo groups. They then conducted experiments on mice’s social preference and self-grooming behaviours.
Researchers also found that the effect of the three-day treatment lasted for three weeks in mice – from the juvenile to late adolescent period. In humans, this is equivalent to several years, researchers said.
These findings build on Dr Yan’s previous research in 2015 which found Shank 3 disrupts how neurons communicate by reducing the function of the NMDA (n-methyl-D-aspartate) receptor, a protein that regulates cognition and emotion.
This causes people to be anti-social, a symptom that is common in people on the autism spectrum.
The new study shows that romidepsin reverse those social deficits by restoring gene expression and function.
Dr Yan said many of the cell mutations that occur in people with autism are a result of chromatin remodelling factors, which are involved in changing the structure of genetic material.
‘The extensive overlap in risk genes for autism and cancer, many of which are chromatin remodelling factors, supports the idea of repurposing epigenetic drugs used in cancer treatment as targeted treatments for autism,’ said Dr Yan.
‘Autism involves the loss of so many genes,’ Dr Yan explained. ‘To rescue the social deficits, a compound has to affect a number of genes that are involved in neuronal communication.’
To do so, the team needed to target histone modifiers, a type of chromaton remodeller that alters proteins called histones that help regulate gene expression.
The anti-cancer drug romidepsin, inhibits histone modifiers.
“In the autism model, HDAC2 is abnormally high, which makes the chromatin in the nucleus very tight, preventing genetic material from accessing the transcriptional machinery it needs to be expressed,” said Dr Yan. “Once HDAC2 is up regulated, it diminishes genes that should not be suppressed, and leads to behavioural changes, such as the autism-like social deficits.”
Romidepsin loosened the chromatin in the nucleus, allowing the genetic material to gain access to the transcriptional machinery so they can be expressed.
Dr Yan and her team found that romidepsin restored the majority of the more than 200 genes that were suppressed in the autism animal model they used.
People with this developmental disability have significant social, communication and behavioural challenges.
Source: Daily Mail