Why is brain tissue donation vital to advancing autism treatment?

This week’s “Got Questions?” response is from Autism Speaks Senior Director for Environmental and Clinical Sciences Alycia Halladay.

I read about BrainNet and your new push to increase postmortem brain donations. Why? What has brain tissue research done for the autism community?

Thanks for the important question. As you know, Autism Speaks helped launch BrainNet to advance the donation and careful management of postmortem brain tissue for autism research. In fact – at the International Meeting for Autism Research (IMFAR) – we joined in announcing the launch of Autism BrainNet’s new donor-registration website.

Why is this so urgent? We have many theories about what causes autism spectrum disorder (ASD) and how early brain development goes awry in affected individuals. Understanding which theories are correct is crucial for the development of treatments as well as identification of practical steps for prevention. Because autism is a neurological disorder, the only way to gain this understanding – definitively – is to study actual brain tissue.

Here are a couple recent discoveries that would not have been possible without studying human brain tissue:

When and where in the brain does autism develop?

No one is saying that all types of autism develop in the same way. But research is uncovering some important commonalities. Earlier this year, an in-depth study of brain tissue by Eric Courchesne and his colleagues found that autism-associated brain changes consistently arise in specific layers of the cerebral cortex during a specific window of prenatal development.

What’s more, the researchers found that the defects occurred in patches rather than across the entirety of the cortex– giving hope that early intervention or other therapies may help children’s brains “rewire” around the problem areas. Further research may advance understanding of how to best enhance such improvement.

The physical evidence of early brain changes also backs a growing body of research linking increased risk for autism to a combination of genetically controlled processes and environmental influences that affect prenatal brain development. Autism Speaks continues to invest in research to identify avoidable environmental risk factors.

Dr. Courchesne’s study also complements earlier brain-tissue research identifying other areas of the brain involved in autism. These include areas of the cerebellum, hippocampus and amygdala.

Using new technologies, researchers are now combining the findings of these brain-tissue studies to build three-dimensional images of the developing brain. These models suggest that multiple brain areas and networks of brain activity are not functioning properly in autism.  Much of this research was made possible by Autism Speaks Autism Tissue Program, which has now become an integral part of been folded into BrainNet.

How might genes and the environment affect risk?

Still other brain-tissue studies provide important evidence of how environmental exposures can affect brain development in ways that may increase autism risk. Examples of these exposures include certain chemicals, stress and the mother’s diet. 

The brain-tissue connection? Analysis of brain tissue has shown that certain genes associated with autism appear to be “methylated” in brain cells. Methylation is an “epigenetic” mechanisms for turning genes on and off at crucial times during development. Importantly, we know that environmental exposures can affect methylation and, so, alter the expression of these pivotal genes.

In a recent study, researchers found that DNA in brain cells from individuals who had autism were methylated, while cells in the same brain areas in individuals who did not have autism were not methylated. This is further evidence that epigenetic mechanisms may put certain individuals at greater risk for ASD under certain environmental circumstances.

While methylation patterns can be studied using blood, the patterns in brain tissue appear to differ in important ways. This is another reason why it’s so important that research be done with actual brain tissue.

Can we turn these findings into treatments?

We’re very hopeful that further research can turn these discoveries into treatments. For example, yet another study looked at methylation of genes associated with ASD.  The researchers focused on a gene called SHANK3, which is the known cause of Phelan McDermid syndrome.  Most children with this syndrome also have autism. In their study, the researchers found that they could control the SHANK gene’s activity with an experimental drug treatment that affected the gene’s methylation.  As we mentioned earlier, methylation is a way that   genes get turned on and turned off. The findings suggest the possibility of reversing the symptoms of autism and Phelan McDermid syndrome with a medication that can “turn on” the SHANK gene. It’s too early to tell. For answers, we need more studies on brain tissue in conjunction with better animal models and eventually clinical studies.

Going forward, donations to BrainNet may be included in President Obama’s unprecedented BRAIN Initiative through a partnership with the Allen Brain Project. The BRAIN Initiative promises to revolutionize our understanding of both typical brain development and the altered development that results in developmental disabilities such as autism.