Anti-cancer drug may alleviate symptoms of autism
New study led by the State University of New York at Buffalo indicates an anti-cancer drug could have the ability to reverse social impairments related to autism.In a paper currently published in the journal Nature Neuroscience, the researchers report how low doses of romidepsin -- a drug approved in the United States for treating lymphoma -- "restored gene expression and reversed social deficits" in a mouse model of autism.
Autism spectrum disorder (ASD), which is a developmental condition, affects behaviour, social interaction, and communication.
Statistics which were compiled in the U.S. suggest that 1 in 68 children have ASD and it's around four to five times more prevalent in boys than in girls.
Although it'spossible to diagnose the disorder at age two, most diagnoses of ASD aren't confirmed before the age of 4.
The economic costsin the U.S. for kids with ASD are estimated to be in the range $11.5 billion to $60.9 billion.
Low doses 'reversed social deficits'
Of all the challenging and catastrophic symptoms which accompany ASD, difficulty interacting with other people and forming connections is especially upsetting and there'spresently no effective therapy.
The new study is regarded as the first to demonstrate that it may be possible to relieve this key symptom of ASD by targeting a large number of genes associated with the disorder.
"We have discovered," says senior study author Zhen Yan, a professor at the Department of Physiology and Biophysics, "a small molecule compound that shows a profound and prolonged effect on autism-like social deficits without obvious side effects ."
This, she considers, is especially important because "many currently used compounds for treating a variety of psychiatric diseases have failed to exhibit the therapeutic efficacy for this core symptom of autism."
In their analysis, Prof. Yan and her groupdiscovered that 3 days of therapy with low doses of romidepsin "reversed social deficits" in mice using a deficient SHANK3 gene, which is a known risk factor for ASD.
The reversal in social deficits lasted for 3 weeks, from juvenile into late adolescence -- thatcan be a vitalphase in mice to developing communication and social skills and is equal to several human decades.
This indicates a similar therapymay be long-lasting in humans, suggest the researchers.
This new study builds on previous work with mice by Prof. Yan and group that demonstrated how loss of SHANK3 disrupts the n-methyl-D-aspartate receptor, which helpsregulate emotion and cognition. The disruption caused difficulties in communication between brain cells and contributed to ASD-related social deficits.
To quantify social deficits in the mice, the scientists put them in controlled surroundings where they could evaluate their preference for social stimuli (such as interacting with another mouse) versus preference for non-social stimuli (for instance,investigating an inanimate object).
The research showed how romidepsin was able to undo the social deficits by restoring the role of genes via an epigenetic mechanism.
Epigenetic mechanisms are genetic processes capable of switching genes on and off and changing their expression without altering their underlying DNA code. Yan states that previous studies have implied that epigenetic alterations might have a largeimpact in ASD.
One of the critical outcomes of this new study is the fact that it proves that it may be possible to target a large number of ASD-related genes with only 1 medication.
Romidepsin is a histone modifier, which is a type of compound that changes the proteins, or histones, that help arrange the DNA in the nucleus.
The medication "loosens up the densely packed chromatin," Prof. Yan describes. The end result is to restore gene expression by making the genes accessible to the molecules whichtranslate their instructions.
With thehelp of genome-wide screening, the researchers found that romidepsin restored gene expression in the majority ofthose 200-andgeneswhich were silenced in the autism mouse model used in the research.
"The advantage of being able to adjust a set of genes identified as key autism risk factors may explain the strong and long-lasting efficacy of this therapeutic agent for autism."