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Annual Letter from the Chief Science Officer

January 05, 2012

The Year in Review

from Autism Speaks’ Chief Science Officer


January 5, 2012

Dear friends,

When I was a college student starting to explore autism research, one of the first studies I read provided strong evidence that autism was mostly a genetic condition. That study, by Michael Rutter and Susan Folstein, looked at 21 pairs of twins, at least one of each pair being affected by autism. It compared identical twins, who share all of their genetic makeup, with fraternal twins, who share around half their genes. It found that when one identical twin had autism, so did the other 83 percent of the time. By contrast, this was true of only 10 percent of the fraternal twins. For the next three decades, it was taken as fact that the causes of autism were almost completely genetic.

That changed this past year with the largest ever autism twin study. Joachim Hallmayer and colleagues at Stanford University found a significantly lower autism concordance between identical twins—just 70 percent. They also found a much higher than expected overlap between fraternal twins—around 35 percent, considerably higher than the 15 percent or lower concordance we know exists between siblings who are not twins. This strongly suggests that environmental influences play a significant role in autism -prenatal influences being among the most likely.

These findings have profound implications, and they would not have been possible without your support for Autism Speaks and its Autism Genetic Resource Exchange (AGRE). AGRE is the world’s largest private genetic database for autism. AGRE staff, who were co-authors on the study, helped recruit the twins for this research, flew to their homes and spent days with each family conducting evaluations and collecting DNA and then provided this information to the researchers for analysis. Their findings are already catalyzing further research on environmental contributions to autism spectrum disorder (ASD), an area of research in which Autism Speaks continues its considerable investments.

The influence of environmental risk factors on genes

Environmental exposures such as toxins, diet and hormones can turn genes “on” and “off,” in effect acting like a genetic mutation.

Among the areas we are investigating is the study of “epigenetics.” Scientists have discovered that environmental influences such as toxins, diet and hormones can turn genes “on” and “off.” Exposure to a chemical, for example, can act like a genetic mutation to essentially silence a gene.

This past year, Autism Speaks hosted the first symposium on Environmental Epigenetics of Autism, bringing together world experts on autism, environmental health research and epigenetics. Together, they explored new and promising avenues for studying environmental influences that may affect gene expression in ways that contribute to ASD risk.

Thanks to your support, we awarded a $450,000 grant to genetic epidemiologist Dani Fallin, of Johns Hopkins University, to study epigenetic changes in the DNA of individuals with ASD. Not only does this research have great potential for deepening our understanding of autism’s causes, it may guide our search for prevention strategies and treatments.

For example, a study published in 2011 by scientists from University of California, Davis, found that taking prenatal vitamins during the months before and after conception appears to lower the risk of having a child with ASD – if the mother or child carries certain genes that increase susceptibility to autism. Such studies highlight the interactions between genetic and environmental factors that are critical to understanding the causes of ASD. It is not “either-or” but research into “both” genes and environment that will provide the answers.

This year we are funding several studies that explore environmental risk factors, including early life exposures to infections and toxic metals with an emphasis on their impact on immune function, as well as studies on the effects of air pollutants and low birth weight/prematurity. (Explore the studies we are funding, here.)

In fact, Time magazine just named the association between low birth weight and autism as one of 2011’s top 10 “parenting” discoveries. The study establishing this link was one of Autism Speaks’ Top 10 Research Advances a year earlier. (See our Top Ten for 2011 here.) In 2011, we funded a study that will follow a large group of low-birth-weight infants to screen for early signs of autism. In the future, close monitoring of low-birth-weight infants for autism risk may become standard practice, and this study will help us identify early signs in this vulnerable group of infants.

In 2011, a study funded by Autism Speaks found that 1 in 38 South Korean schoolchildren has an autism spectrum disorder.

The rapidly increasing prevalence of ASD is another reason why we continue to fund and advocate for research on environmental risk factors. In 2011, we were stunned by the results of a study we funded to determine the prevalence of ASD in South Korean schoolchildren. The study found a prevalence of 1 in 38. Why the high number? It is possible, but unlikely, that the prevalence in South Korea is many times higher than here in North America. A more likely explanation is that the methods used in the South Korean study, which involved direct screening of a total population, identified many previously undiagnosed children. By contrast, the CDC’s current prevalence estimate of 1 in 110 children is based on children identified through therapy records, which may underestimate true prevalence.

To follow up on these findings, we are now supporting a total community autism screening study in the United States, through the CDC’s Autism and Developmental Disabilities Network. This research—again made possible through your support—promises to provide more accurate estimates of ASD prevalence in United States. Just as important, it will explore why some—perhaps many—children with autism are not being diagnosed and, so, not receiving the services they need. Indeed, our South Korean investigators found many undiagnosed children struggling in school and having difficulty forming friendships. These kids were not receiving the proper services and supports they needed, and we need to find out if a similar situation is occurring here in the United States.

If this turns out to be the case, we must then determine how we can help ensure that all children with ASD are getting the support they need. We know, for example, that children from ethnic minority backgrounds tend to be diagnosed at older ages and that doctors are less likely to provide an appropriate diagnosis when parents in this group express their concerns. We are investing in research to address these disparities in diagnosis and services.

Progress in understanding ASD biology points to new treatments

As we continue to sleuth the causes of ASD, we are also learning more about its underlying biology in ways that point toward potential new treatments for the core symptoms of ASD.  For example, this past year, Autism Speaks funded a landmark study looking at levels of inflammatory markers in the blood of young children with ASD. The researchers found elevated levels of these inflammatory markers in children with a history of regressive ASD, with increasing levels of inflammation associated with more impaired communication and repetitive behaviors. These findings suggest that ongoing inflammation—indicating immune activation —may play a role in some forms of autism. To guide research in this area, we hosted a think tank on Immunology and Autism—gathering leading immunologists who offered recommendations on promising new avenues of research. In the coming year, we are also funding research aimed at identifying biomarkers of immune dysfunction in children with autism and associated gastrointestinal (GI) disorders.

Each of these autism risk genes is rare, but most involve a handful of brain pathways and appear to affect how neurons communicate with each other.

Although we now understand that autism is not one condition but many, research is also revealing that many forms of autism share underlying biological similarities. In the last year, for example, scientists discovered numerous gene changes that increase risk for autism, most in the form of small DNA deletions. Though these autism risk genes were quite varied—and each by itself rare—most involved a handful of pathways in the brain. Most of these pathways affect the manner in which neurons communicate with each other.

Our scientists are now working to discover “biomarkers” that can identify subtypes of autism that may respond to different medicines.

Proper function of the junction, or synapse, between neurons requires a delicate balance between excitatory and inhibitory neurotransmitters. This balance appears to be disrupted in autism, with some forms of autism involving over-excitation at the synapse and other cases involving under-excitation. Now, researchers are using these insights in clinical trials to test how various medicines might restore normal synapse function in individuals with autism linked to specific genetic mutations, as well as in individuals with “idiopathic autism” where the cause of their autism is not known. We look forward to the results of these trials in the coming year.

An important part of the research we are funding is the identification of “biomarkers” that can distinguish subtypes of autism that may respond to different medicines. For example, we funded a project to develop a blood test that could be used to identify individuals who could potentially benefit from PI3K/mTOR targeted therapies. The “mTOR” cascade is one of the common pathways we see emerging from autism genetic studies.

In December of 2011, we announced the funding of studies that will test, in animal models, five new compounds designed to reduce core symptoms of autism, most of which aim to improve synaptic functioning.  We are also funding several postdoctoral fellowships to support the work of promising young scientists starting their career in this area of “translational medicine.” Each fellow is required to divide his or her time between the laboratory and the clinic.   

These fellowships are part of Autism Speaks Translational Medicine Research Initiative, a broad program devoted to developing new methods for preventing, diagnosing and treating autism. Translational medicine refers to research focused on moving basic science discoveries from the laboratory into the real world, or “bench to bedside.”

This past year, we hired two outstanding scientists with backgrounds in medicine development—neuroscientist Robert Ring and child-adolescent psychiatrist Joe Horrigan—to lead our translational medicine efforts. Already they are finalizing agreements to produce superior animal models for drug testing in the United States and to collaborate with the European Union and its pharmaceutical partners to speed the development of drug discoveries. This public-private partnership will provide $55 million over 5 years for the development of autism medicines, most of this funding coming from the European Union. This is the largest single research program in the history of autism science.  

Autism Speaks Translational Medicine Research Initiative focuses not only on the safe development of new medicines—a process that can take several years. It is also enhancing efforts to test medicines FDA-approved for other conditions for their ability to ease autism-associated medical issues such as anxiety and sleep disorders.

Our approach is to maximize our supporters’ investment by providing “seed” funding for promising new ideas that may be considered too “risky” for large-scale investment by the National Institutes of Health or for-profit interests. Such funding often produces a tremendous return on investment by enabling successful investigators to win further funding. As evidence, Autism Speaks investment of $16 million in completed research grants has already leveraged an additional $150 million in federal and other funding for autism research.

Improving lives today

Further leveraging your investment, physicians who are part of Autism Speaks Autism Treatment Network (ATN) garnered $12 million in federal funding to serve as the nation’s Autism Intervention Research Network on Physical Health (AIR-P). The ATN is a collaboration of 17 medical centers, which care for some 22,000 children with autism each year. The AIR-P funding supports the ATN’s clinical research on medical conditions associated with autism, the training of physicians and the development of guidelines and tool kits for both physicians and families.

Currently, over 4,000 children with autism are part of the ATN patient registry, and Autism Speaks recently received funding from the NIH to develop an ATN biorepository. This valuable collection of blood samples will be a vital resource that will allow tailoring new treatments to the distinct needs of different subgroups of children with autism.

In 2011, the ATN released five autism tool kits for families and clinicians, including a medication decision aid for families and guides for improving sleep habits and enhancing communication with visual aids. In the coming months, look for more ATN tool kits including a guide for dentists and others for physicians diagnosing and treating associated medical conditions such as gastrointestinal disorders.

Also of immediate benefit to our families were the important findings published in 2011 by Autism Speaks Baby Siblings Research Consortium. We learned that autism recurs in families at a much higher rate than previously realized: If one or more children in a family is diagnosed with autism, the chances that a baby sibling will develop the disorder is around 1 in 5, more than double previous estimates. This information underscores the importance of closely monitoring the development of infants and young children with older siblings on the autism spectrum and is already influencing such practices among pediatricians. Fortunately the past year’s research also delivered validation of a practical method for autism screening at the 1-year, well-baby checkup.

As we learn to recognize autism earlier and earlier, it becomes increasingly important to offer families effective early interventions appropriate for even young infants. Autism Speaks is investing in several clinical trials to develop toddler interventions. An additional challenge is ensuring that all families have access to an early diagnosis and intervention. Unfortunately, although we now have validated methods for recognizing autism symptoms in infants, the average age of ASD diagnosis in the US remains close to 5 years. Even after diagnosis, many families face obstacles such as lack of insurance coverage and appropriately trained professionals in their communities.

Our mission is to improve the lives of all those struggling with ASD. We cannot consider the job done until we see effective treatments implemented in the broader community.

These hard realities continually remind us that Autism Speaks’ mission is not simply to discover and develop improved methods for diagnosis and treatment. It is to “improve the lives of all those struggling with ASD.” This means that we cannot consider the job done until we see the broad implementation of the best practices that our researchers develop and validate. Our goal is to lower the age of diagnosis of ASD and increase the number of children receiving high quality services.

This is why we are now investing in studies, both in the United States and abroad, that will explore innovative ways to increase access to early diagnosis and intervention in low-resource communities. These methods range from web-based professional consultations to training parents to deliver home-based therapies.

A lifetime perspective: New initiative targets improving quality of life for adults with ASD

While early intervention can change the life trajectory of individuals with ASD, longitudinal studies of adolescents and adults with ASD show that a successful transition to adulthood requires appropriate services and support. Remarkably, there has been little research on transition services, successful employment and the promotion of physical health and positive adult social relationships. Indeed, we still know little about the health and quality of life of persons with autism as they reach middle and older ages.

This past year, a study conducted by Autism Speaks staff showed that mortality rates of individuals with autism are much higher than that of the general population, especially among those with autism and epilepsy. We are now exploring why this is so, with the goal of developing strategies for prevention.

We have launched an Initiative on Adults with ASD that includes advocacy for services, tool kits and research on adult services and outcomes. Later this month, we are bringing together a group of our funded researchers to share ideas about their work on improving quality of life for adults with autism. Their funded projects explore new methods for improving social relationships, health, and successful employment. 

I hope you are as excited as we are about the discoveries that are being made and the wide range of research we are funding, all dedicated to improving the lives of individuals with ASD and their families. The pace of discovery is rapidly increasing, and our fellowships are bringing some of the brightest scientists into the field.

None of this would be possible without the support of thousands of families who have donated to this effort. Thank you sincerely for the hope and help you are providing.

In closing I would like to invite you all to join me and our head of medical research, Joe Horrigan, in a new series of monthly webchats, “The Doctors Are In,” at 3 pm Eastern on the first Thursday of each month, beginning Jan 5th. Follow this link, or look for the webchat tab on the Autism Speaks Facebook page.

My very best wishes for the New Year!