January 8, 2009
On a sunny afternoon last June, the moving van arrived to our new home in North Carolina only to get stuck in the ditch while attempting to negotiate the driveway. Minutes later, a policeman arrived to direct traffic while a very large tow truck pulled the moving van out of the ditch. While we waited anxiously, I struck up a conversation with the young police officer who eventually asked what brought us from the Northwest to the Southeast. I explained that I had taken a new job with an organization called Autism Speaks whose headquarters are located on the east coast. His expression then became serious and he quietly stated
Chief Science Officer
that his first son had been diagnosed with autism and now he was concerned about his second child. For the next half hour or so, we talked about his concerns for his youngest child and his hopes and dreams for his first. That moment reaffirmed my decision to take my new job as Chief Science Officer at Autism Speaks – it captured what our work at Autism Speaks is all about: Making life better for individuals like that young police officer and his children.
It's not surprising that one of the first people I spoke with when I arrived in North Carolina was someone struggling with autism in their family. The high prevalence of autism means that autism touches virtually everyone. Fortunately, because of scientific research, increased awareness, and advocacy, this father was not only aware that his young son has autism and already understood that his second child was at higher risk for autism; he will also be armed with a road map for how to best help both of his children. Living in North Carolina, he can take advantage of the state-funded early diagnosis program available for free to all who live in this state. But, we still have a long way to go. The road map is still filled with detours, dead ends, and many bumps in the road. For some parents, the road map leads to a very positive outcome for their child, whereas for others, the road map seems to offer little help at all. Looking back on 2008, how far have we come? And what challenges lie ahead for 2009? Later, we will be highlighting the “Top 10 Autism Science Achievements” in our e-Speaks newsletter. For now, I offer one scientist's perspective on the scientific achievements of last year and a brief look forward to the year ahead.
What did we learn in 2008 about what causes autism? The year started out with a bang when Susan Christian, Ph.D. (from University of Chicago), Mark Daly, Ph.D. (from the Autism Consortium) and Steve Scherer, Ph.D. (from the Autism Speaks-funded Autism Genome Project) almost simultaneously reported that DNA deletions and duplications on chromosome 16 explain the cause of 1-2 percent of the cases of autism. Individuals who have deletions in this chromosomal region have a high likelihood of developing autism. Taken together with other known genetic
Mark Daly, Ph.D.
Assistant Professor, Harvard U.
disorders that cause autism, we now can account for the genetic cause of about 10-15 percent of cases of autism.
There are about 25 genes in this region of chromosome 16 that are related to brain function. The search is now on for which of those genes might be causing autism. Some hospitals are now regularly screening for these types of deletions and duplications as part of the standard diagnostic work-up of a child suspected of having autism.
Three lead scientists and their co-workers (Dan Geschwind, M.D., Ph.D., Matthew State, M.D., Ph.D., and Aravinda Chakravarti, Ph.D.) reported new evidence that a gene called Contactin Associated Protein-Like 2 (CNTNAP2) is a risk gene for autism, most likely influencing the development of neural circuitry for language development in males. Previous research had shown that a rare mutation in CNTNAP2 is associated with seizures, language delay, and autism. Children with this rare mutation typically have onset of seizures between 14-20 months of age, followed by regression in language, learning ability, and social skills. Dr. Geschwind, lead
Dan Geschwind, M.D., Ph.D. Professor, UCLA
author of one of these reports, is a member of Autism Speaks' Scientific Review Panel and Scientific Advisory Committee. The research on CNTNAP2 utilized the Autism Speaks-supported Autism Genetic Resource Exchange (AGRE) data. It's remarkable to realize that only a decade ago, we didn't even know where to look for genes related to autism. Now, scientists have identified several specific autism risk genes. This has happened, in large part, because scientists from around the world began pooling together their genetic data in large collaborative studies. The AGRE data base and AGP project –both large genetic data bases funded by Autism Speaks – have played a central role in these discoveries. As we learn more about autism susceptibility genes, we will be able to screen the second child in the family for these genes so that early intervention can begin as soon as possible. Furthermore, by understanding which genes are involved in autism, we will begin to understand the biological basis of autism.
2008 also witnessed several reports focused on possible environmental risk factors for autism. Among the environmental factors reported to be associated with risk for autism were mother's use of epileptic drugs during pregnancy, premature birth, prenatal exposure to high levels of pesticides or insecticides, seizures during infancy, living in regions that experience high levels of precipitation, and being born in April, June, and October. At first blush, some of these environmental factors are hard to understand. Why would there be a higher prevalence in regions that get more rain? One factor might be
Craig Newschaffer, Ph.D.,
Professor, Drexel University
a deficiency in vitamin D. There is ample evidence that vitamin D has an important role in both brain development and function. Last year, Autism Speaks funded a study to follow up on this hypothesis. How about being born in April, June, or October? This novel finding was reported in a paper by Andy Zimmerman, M.D. and Craig Newschaffer, Ph.D. and their colleagues. Dr. Newschaffer is an epidemiologist who is a member of Autism Speaks' Scientific Advisory Committee and Scientific Review Panel. Dr. Newschaffer and colleagues note that the presence of seasonal trends in autism spectrum disorder (ASD) supports a role for non-genetic factors operating during the pre- or peri-natal period. Such factors could be viral infections, temperature or hormonal fluctuations, and toxic environmental exposures, among others.
Perhaps no other report in 2008 made a bigger impact than the case of Hannah Poling, a child with mitochondrial disorder who developed autism after receiving multiple vaccinations. A vaccine injury compensation decision acknowledged that vaccines may have contributed to the development of autism in young Hannah. The case led to increased interest in the role of mitochondrial disorder as an underlying condition that might make a child more vulnerable to adverse effects of vaccines. Since the ruling, Autism Speaks has funded two of the world's experts on mitochondrial disorder, Doug Wallace, M.D. and Richard Haas, M.D. to conduct a large scale study of the prevalence and nature of mitochondrial disorder in autism. Dr. Wallace is a member of Autism Speaks' Scientific Advisory Board.
Like pieces of a jigsaw puzzle falling into place in one corner of a large and complex picture, the genetics research of the past decade or so is beginning to shed light on the biochemical basis of autism. Specifically, several findings suggest that autism and related developmental disorders that often result in autism, such as Rett Syndrome, are caused by abnormalities in the connections between neurons (synapses). There are several ways synaptic functioning can be affected. The goal is to eventually be able to intervene and correct the biochemical abnormalities so that synaptic functioning can return to normal. One of the exciting findings reported last year did just that in a mouse model of tuberous sclerosis. Tuberous sclerosis (TSC) is a genetic disorder caused by mutations in the TSC1 or TSC2 gene that results in mental retardation, autism, and seizures. By inactivating this gene in mice, it is possible to mimic the TSC syndrome. Such mice have learning and memory problems. Alcino Silva, Ph.D. and colleagues at UCLA showed that these learning deficits are related to hyperactivity of a biochemical pathway in the hippocampus, a brain structure involved in learning and memory. They then introduced a treatment that inhibited this pathway which eliminated the learning deficits in the mouse. This example of “recovery” from a genetic condition represents a true paradigm shift in our thinking about developmental disorders. It was previously thought that it would not be possible to reverse a developmental syndrome. These results suggest that the pathology is reversible – the brain circuits affected do not atrophy but rather remain in an immature state, and they can be later activated in such a way to repair the syndrome's consequences. This report, and others documenting similar results for Fragile X and Rett Syndrome, suggest that potentially functional brain circuitry is lying dormant that can be corrected through biochemical manipulation. Last year, Autism Speaks funded Adrian Bird, Ph.D. from the United Kingdom to extend this type of research in a mouse model of Rett syndrome. Although the translation from a mouse model to a treatment for humans will be extremely challenging, these findings are motivating scientists world-wide to pursue precisely that goal. In fact, human clinical trials for Fragile X syndrome and TSC, based on the mouse model work, were launched last year. Looking ahead in 2009, this area of research promises to be one of the most exciting.
There is currently no molecular marker or biological test that is capable of identifying autism at an early age. Last year, however, Jun Tan, M.D. Ph.D. and colleagues reported a potential biomarker for autism that can be measured from a blood spot. The biomarker is secreted amyloid precursor protein-alpha (sAPP). In their study, they found that 60% of children with autism showed elevated sAPP. Another potential early biomarker was reported by Judy Van de Water, Ph.D. and Lisa Croen, Ph.D. Dr. Croen is a member of Autism Speaks' Scientific Advisory Board. These scientists measured maternal antibody reactivity to the fetus
Judy Van de Water, Ph.D.,
Professor, University of California, Davis
during mid-pregnancy in mothers who had participated in a prenatal screening program in California. They found that mothers whose children developed autism had higher levels of this immune marker during pregnancy. Similar results were reported from a group at Johns Hopkins University. Autism Speaks continues to fund a wide range of research on early detection of autism based on both behavioral and biological markers, including how these immune markers interact with genes identified as risk factors.
Earlier detection and treatment will certainly result in better outcomes for individuals with autism. In 2008, the first peer-reviewed scientific articles were published on the topics of recovery from autism and prevention of the disorder through early intervention. Debby Fein, Ph.D., a member of Autism Speaks Scientific Advisory Board, has been documenting cases of recovery from autism for the past few years. Dr. Fein reviews evidence that between 3-25 percent of children no longer are diagnosed with autism and have normal cognitive, adaptive, and social abilities. Early predictors of recovery include higher IQ, and
Deborah Fein, Ph.D., Professor, University of Connecticut
improved receptive language and imitation skills, but not necessarily the severity of autism symptoms. Most cases of recovery are the result of behavioral intervention. The second article, which I wrote, was the first to describe a model of prevention of autism via early detection and early intervention. The model describes how environmental enrichment through early intervention can mitigate the influences of genetic and environmental risk factors and alter the trajectory of brain development such that a subgroup of children never develops the full blown syndrome of autism.
Autism Speaks efforts directed toward increased awareness and insurance coverage for autism services continue to be high priority at our organization. Increasingly, however, we are also focusing our efforts on diagnosis and increasing access to services across the life span. Families of individuals with autism continue to have difficulty gaining access to care, even when services are available, and the costs are prohibitive. A report published in 2008 found that health care expenses associated with autism rose 20 percent from 2000-2004. Another report noted that families who have a child with ASD have an annual loss of $6,200 or 14 percent of their income. In yet another 2008 report, Michael Kogan, Ph.D. and colleagues noted that, compared to children with other special health care needs, children with autism are more likely to have many unmet needs for health care and family support. Employment, health, and emotional well-being of parents are all negatively affected. Parents are often required to stop or reduce work to care for their child. Thus, it is crucial that Autism Speaks continues to advocate for improved care, access to appropriate services, and financial and other types of support for families.
As new methods for autism detection and treatment become available, it is essential that we consider how these new findings are going to be disseminated to the practicing clinician. Discovery of a biomarker for early detection or a new medical treatment for autism will only have impact if clinicians in the community are aware of this information and use it. For example, in 2008, it was reported that rates of mortality in individuals with autism are twice that of the general population. Epilepsy and infectious disease were found to be the most common cause of mortality. This suggests that mortality in autism could be reduced with appropriate access to care and physician training.
One of my goals as CSO at Autism Speaks is to facilitate the dissemination of scientific discoveries into general practice. Last year, we instituted at new research portfolio focused on dissemination and policy. The science team at Autism Speaks is already working on several efforts aimed at improving dissemination. The Autism Treatment Network (ATN), a network of autism treatment centers funded by Autism Speaks, is focused on improving medical care for children with autism. Each ATN site has a multidisciplinary team that includes a pediatric gastroenterologist, sleep specialist and metabolic
Daniel Coury, M.D.
Medical Director, ATN
specialist. The goal is to define best practices in medical care for autism and increase access to improved medical care by publishing guidelines and training practitioners. The ATN received a major boost in funding in 2008 when it was awarded a $12 million dollar grant from the federal government to investigate nutritional and sleep problems in children with autism and develop guidelines for medical care. Last year, the ATN also had the good fortune of hiring an outstanding medical director, Daniel Coury, M.D. Dr. Coury brings with him a wealth of clinical and administrative experience, having served as the chief of developmental and behavioral pediatrics at the Nationwide Children's Hospital and the Ohio State University. Other Autism Speaks efforts on dissemination have involved collaboration with the NIH and other professional organizations, and are focused on developing and implementing large scale models for training in screening, diagnosis, and treatment. To ensure that the results of all research funded by Autism Speaks is communicated world-wide, we now require all grantees to post their publications on PubMed Central, an on-line database that provides free access to biomedical publications. In doing so, Autism Speaks became the first US-based non-profit advocacy organization to require this of their grantees.
A look back on 2008 and look forward to 2009 would not be complete without noting the financial crisis that has affected the world economy. The crisis affects us all – families, individuals with autism, scientists, clinicians, businesses and nonprofit foundations. One of my biggest concerns is the loss of scientific momentum in the field of autism research. The last decade has witnessed a dramatic increase in the number of scientists who are turning their creative minds and efforts toward discovering the causes and effective treatments for autism. Many of these scientists are young people who are just starting their careers and rely on Autism Speaks to fund their fellowships and research. As a science, autism research is just now becoming mature enough to yield what promises to be truly ground-breaking discoveries. With the increased awareness of autism, government officials and universities are now paying attention to autism, devoting more resources, and investing in state-of-the-art autism centers of excellence. President-elect Obama has expressed his commitment to improving the lives of individuals with autism through research and improved access to high quality services. Now, more than ever, unifiedsupport for research and advocacy efforts has the potential to yield real change in the lives of individuals with autism and their families.
I fully recognize that, among the autism stakeholder community, there will always be real differences of opinion regarding what kinds of research are most important. I am reminded of another event of 2008 that occurred shortly after I started as CSO. I was delivering my first major talk on behalf of Autism Speaks, a bit chagrined because I had developed laryngitis. At the end of the talk, a man clearly agitated by my talk asked me why we wanted to cure people with autism. My talk was viewed as offensive to this man who was content to have autism and was proud of the unique and special gifts that people with autism bring to our world. Then, another man jumped up, equally agitated and began to angrily describe how his brother had suffered because of autism. He described how his brother had never learned to speak and how his brother's life had been greatly diminished by autism. In a whisper due to my laryngitis, I remarked that the very different and valid perspective that each of these men has reflects the tremendous heterogeneity among people with autism. Yet, both men have one thing in common – the desire to reduce suffering for people with this condition. Indeed, my email inbox is filled each day with a diversity of perspectives and opinions about what Autism Speaks should be doing. I read each of these emails with great interest. It is my belief, however, that we must strive to achieve one strong voice while, at the same time, allowing there to be a wide range of opinions and perspectives. I listen carefully to every voice, knowing that history has taught us that scientific truth is often what you least expect to find.
I believe we can maintain and accelerate the momentum we have achieved in autism science despite the economic challenges we face. I hope that every supporter of our efforts will stick with us through this difficult economic period, by whatever level of support is possible, and that every supporter will reach out to a friend or colleague to ask for their support so we can maintain our efforts by increasing the number of people who are devoted to these efforts.
Our promise to you is that our focus will remain unwavering. Scientific efforts will continue to focus on discovering the causes, treatments, and cure for autism, and disseminating that knowledge into the larger world to affect real change for all individuals with ASD and their families. Autism Speaks advocacy efforts will continue to focus on reducing stigma, improving quality of life, and increasing knowledge and awareness of autism. I hope you will join with us in that effort.
With best wishes for the New Year,
Chief Science Officer