In a breakthrough, A* scientists have successfully unravelled secrets of autism, which can possibly pave the way for finding drug to cure this complex disease. Scientists studying autism applied a novel epigenomic sequencing approach to find possible causes of the disorder. This finding has been published in the scientific journal Cell.
The team led by scientists from the Agency for Science, Technology and Research's (A*Star's) Genome Institute of Singapore (GIS) along with scientists from the United States and Europe completed the project in about six years.
The scientists found certain chemical changes in the brain tissue samples they took from patients of autism and compared with those of non-autistic individuals. They found that there were 5,000 changes in the epigenome or DNA packaging of people with autism. What surprised the scientists was that these changes were mostly consistent across the tissue samples taken from individuals with autism. The discovery could pave the way for developing a drug to treat the disease in the future.
Although autism is generally believed to be a heterogeneous collection of distinct diseases, the scientists found that epigenomic aberrations in the brain cells of autistic individuals were surprisingly homogeneous, thus opening new avenues for treatment.
Autism is an umbrella term for several brain disorders that have three symptoms in common: altered thought and imagination processes, social impairment and communication deficits. Despite massive worldwide DNA sequencing of autism patients, the causes of this disorder are still poorly understood due to its complexity. With no common disease mechanism known, it has been difficult to develop effective drugs that could treat majority of autism patients.
Dr Shyam Prabhakar, study’s senior author and Associate Director of Integrative Genomics at the GIS said, “In this study, the researchers used a method, known as epigenome profiling, to characterise thousands of gene control elements across the genome in both healthy individuals and autism patients. Uniquely, they focused on epigenomic changes to DNA packaging molecules in specific regions of the brain. By comparing these two groups, the team discovered for the first time that thousands of control regions behave differently from those of healthy subjects. These elements act as an autism-specific signature and could explain how autism develops in majority of patients. Importantly, this finding opens the possibility of treating autistic individuals with “epigenetic drugs” that alter the epigenomic profiles of cells.
He further informed, “ For this study, we had to combine deep knowledge of the biology of autism with cutting edge experimental techniques and highly precise data analysis methods.”
In response to a specific query from Connected to India regarding introduction of genomics into medicine, Dr. Shyam Prabhakar said, “Genomic medicine is still new, but it is rapidly making its way into the clinic. Some leading academic medical centres in the US, for example, routinely use genomic tests. Our study is research rather than clinical genomics. Our goal is to achieve a better understanding of autism at the molecular level, because you need that to design new treatments.
On another query regarding talk of a new method being available to study any disease and can these be used to cure diseases like cancer, diabetes, Dr. Shyam replied, “Our method is a research tool – it does not cure autism . The method can be used to understand the molecular basis of other diseases as well. This research will, we hope, pave the way for developing new cures.”
The study on the autism project also involved researchers at the University of California at Los Angeles (UCLA, US), the University of Exeter (UK) and King’s College London (UK). The US team was led by Prof Daniel Geschwind, Director of the UCLA Center for Autism Research and Treatment, and the UK team was led by Jonathan Mill, Professor of Epigenetics at the University of Exeter.
GIS Executive Director Prof Ng Huck Hui said, “This is a major breakthrough for the research community because the method can now also be applied to other diseases. This work on epigenomics clearly illustrates the importance of epigenetic signatures in linking the critical genome regulatory loci to disease states."
Dr. Shyam Prabhakar is presently Associate Director, Integrative Genomic at the Genome Institute of Singapore. He obtained his PhD from Stanford University. His research focuses on gene-regulatory mechanisms of human diseases. Dr. Shyam’s research laboratory at the Genome Institute of Singapore uses a combination of high-throughput omics assays (wet-lab) and data analytics (dry-lab) to study gene-regulatory mechanisms of human diseases. Major achievements include the first large-scale study of disease-causing genetic variants that affect histone acetylation and the first unified signal-processing method for peak detection in whole-genome profiling data.