Social Difficulties of Autism Improved with Anti-Cancer Drug

Autism social difficulties illustrated by girl sitting next to teddy, their backs to the camera

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Social difficulties may be the painful behavioral symptom we most associate with autism. But what if there were a drug that could correct this symptom and make it easier for people with autism to socialize? It seems that there may indeed be such a drug, according to the newest autism research published March 12, 2008. Researchers at the University of Buffalo found that brief treatment with very small doses of an anti-cancer drug, romidepsin, not only improved social skills in animals with autism, but that the effects lasted long-term.

Until now, it seemed impossible that such a drug could exist, let alone that a single such drug could be enough to make a difference. Now, however, there is evidence that the behavioral symptoms of autism spectrum disorder (ASD), can be improved by targeting groups of genes known to be involved in the disorder. In this study, mice missing the gene known as Shank 3 (the absence of which is a significant risk factor for ASD), were given a three-day, small-dose treatment with the anti-cancer drug, and the effects lasted a full three weeks.

Why is a three-weeks-long reprieve from social deficits (deficiencies) considered a triumph? Well, we’re talking mice here, not humans. In mice, three weeks is a long time, and spans childhood through late adolescence, a crucial time for developing communication and social skills. Three weeks in mice is the equivalent of several years in a human. Which is why the UB researchers believe that the effects of this brief, low-dose treatment may last many years in people with autism.

“We have discovered a small molecule compound that shows a profound and prolonged effect on autism-like social deficits without obvious side effects, while many currently used compounds for treating a variety of psychiatric diseases have failed to exhibit the therapeutic efficacy for this core symptom of autism,” said Zhen Yan, PhD, a professor in the Department of Physiology and Biophysics at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo, and senior author for this study.

Shank 3 and Social Deficits

This new research trial actually builds on earlier work dating back to 2015. At that time, researchers found that the missing Shank 3 messes up communication between neurons in the brain by affecting the function of a brain receptor known as NMDA (n-methyl-D-aspartate), a crucial factor in the regulation of cognition and emotion. Without Shank 3, the brain has difficulty understanding social cues. This results in the social skills difficulties that are common to those with autism.

In the latest study, UB scientists discovered that a very low dose of romidepsin could reverse these social deficits by restoring gene expression and function. Romidepsin works through epigenetics, which serve as a sort of on/off switch for genes. Dr. Yan notes that human genetics research suggests that epigenetic impairment plays a big role in autism. A number of genetic mutations seen in autism, explains Yan, are due to chromatin remodeling factors, which change the structure of chromatin, gene material contained in the cell nucleus that condenses into chromosomes.

“The extensive overlap in risk genes for autism and cancer, many of which are chromatin remodeling factors, supports the idea of repurposing epigenetic drugs used in cancer treatment as targeted treatments for autism,” said Yan.

Social Deficits/Missing Genes

The researcher and her team knew that chromatin regulators were crucial to treating the social difficulties of ASD, but the problem was how to target many of them at one time. “Autism involves the loss of so many genes,” explained Yan. “To rescue the social deficits, a compound has to affect a number of genes that are involved in neuronal communication.”

Yan and her colleagues decided to look at histone modifiers, a type of chromatin remodeler that modify proteins called histones. Histones help to organize the genetic material in the nucleus so that gene expression can be regulated. The UB reseachers knew that a histone modifier might be effective in targeting the many genes that are altered in autism.

Loosening Up (Those Social Skills)

The scientists focused on histone deacetylase (HDAC), a class of histone modifiers that play a critical role in remodeling chromatin structure regulating transcription in targeted genes. “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 Yan. “Once HDAC2 is upregulated, it diminishes genes that should not be suppressed, and leads to behavioral changes, such as the autism-like social deficits.”

As the researchers found, however, the anti-cancer drug romidepsin, suppresses HDAC, turning down the volume on the HDAC2, which allowed those genes needed for signaling between the neurons, to do their thing. “The HDAC inhibitor loosens up the densely packed chromatin so that the transcriptional machinery gains access to the promoter area of the genes; thus they can be expressed,” said Yan.

Lo and behold, Yan and team found that romidepsin rescued gene expression across the board, targeting all the risk factors/altered genes at once. In fact, when Yan and her co-authors mapped it all out, they saw that romidepsin restored function in most of the more than 200 genes that are suppressed in the autism animal model used by the researchers.

“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.” Yan explained.

How Long A Wait??

The scientist and her research team plan to continue looking into autism treatment drugs. Parents of children with autism, meanwhile, can only wonder how long it will be until romidepsin will be authorized as a safe treatment for human beings. The wait is bound to be long and painful.

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Journal Reference:

  1. Luye Qin, Kaijie Ma, Zi-Jun Wang, Zihua Hu, Emmanuel Matas, Jing Wei, Zhen Yan. Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibitionNature Neuroscience, 2018; DOI: 1038/s41593-018-0110-8

University at Buffalo. (2018, March 12). Autism’s social deficits are reversed by an anti-cancer drug: Using an epigenetic mechanism, romidepsin restored gene expression and alleviated social deficits in animal models of autism. ScienceDaily. Retrieved March 20, 2018 from


Author: Varda Epstein

Varda Meyers Epstein is a mother of 12, communications writer, and education blogger at the Kars4Kids blog.

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