Top Ten Autism Research Findings of 2010 - Autism Speaks

[Autism Speaks] Documents Progress to Discover Causes and Treatments for Autism Spectrum Disorders

NEW YORK, N.Y. (January 25, 2011­) – Autism Speaks, the world's largest autism science and advocacy organization, has released its annual list of the 10 most significant science achievements to have impacted autism during the previous year. Every year, Autism Speaks documents the progress made toward its mission to discover the causes and treatment for autism spectrum disorders, and identifies the 10 most significant research achievements to have impacted autism during the previous year. The 2010 list contains important results from clinical and epidemiological research together with advances in gene discovery and effective treatments which will combine to shape the future of autism research for 2011 and beyond. “Not only has the research community continued to make significant findings on the underlying causes of autism spectrum disorders, work has progressed on effective treatments to improve the quality of life of people with autism,” explained Autism Speaks Chief Science Officer Geraldine Dawson, Ph.D. “While we are indeed making progress, progress is not nearly fast enough and we need more answers.”

“It is imperative that the federal government increase funding for autism research, and reauthorize of the Combating Autism Act so we understand the causes of autism andhow best to help individuals with autism lead productive and independent lives,” stated Autism Speaks President Mark Roithmayr. “I applaud the thousands of families nationwide who joined Autism Speaks Walks and raised funds to support autism research efforts, enabling us to move forward,” Roithmayr added. “Working together – families, scientists, professionals, government officials – we are making progress through science and advocacy.”

With input from Autism Speaks' Scientific Advisory Committee (SAC), Autism Speaks science staff culled through thousands of publications to arrive at these choices. The 2010 compilation is designed to be considered in its entirety and is not arranged to suggest a ranking. “We will remember 2010 as a tipping point in autism research,” stated Autism Speaks SAC member Gary Goldstein, “The papers selected here demonstrate the power of advanced technologies in molecular biology, brain imaging and patient evaluation to provide new insights into the biology of autism. These achievements give great hope for moving the frontiers forward for treatment and prevention of autism.”

As 2010 opened, autism science was the focus at the highest levels of the American research establishment with a landmark meeting hosted by Francis Collins, M.D., Ph.D., Director of the National Institutes of Health. The meeting fostered a spirit of respectful collaboration for autism advocacy groups working together to achieve a common goal of supporting the research that will improve the lives of those living with autism spectrum disorders (ASD). The pool of significant advances in autism science in 2010 suggests that scientists and clinicians are indeed up to the challenge. Here, we highlight 10 of those advances, which include improved treatments and better means of screening for ASD, new clinical care guidelines and a greater insight into the underlying biology of autism.

Technological Advances in Measuring Language Development
Easy to use devices could be helpful in autism screening

Children's early language development has always been a challenge to measure. So, therapists have historically relied on their trained ears and the use of paper-based assessments. A recent technological advance may hold the key to future language assessment. A group of researchers from the U.S. and Austria has been using an all-day recording device (see image above) to make naturalistic recordings of children's vocalizations. They have been recording and analyzing syllable patterns and found that they can reliably distinguish groups of children with autism, children with language delay and typically developing children.

The device itself weighs about one eighth of a pound, can be worn on the child's clothing and makes recordings of the child's natural speech across a whole day. The data the study team collected included 1,486 all-day recordings, from 232 children with more than 3.1 million child vocalizations. The rhythm of the vocalization and the pattern of syllables were analyzed. The study team looked at whether the vocal patterns predicted later language development and also whether the speech pattern could reliably differentiate the three different groups of children.

Vocalization patterns of children with autism were characteristically different from those of typically developing children, and to a lesser degree the analysis also differentiated children with autism from children with language delay. The characteristic that most reliably differentiated the groups was the ability to break down the vocalization into syllables. The ability to form syllables was a significant predictor of future language development.

This technology offers an exciting opportunity to identify children whose language development may be atypical and could be at risk for autism. If further independent studies demonstrate its efficacy, the portability of this technology and its relative ease of use may offer another helpful screening tool for autism. This technology also has potential to be used alongside traditional methods of screening and diagnosing children with autism to increase the reliability of diagnostic assessments. Therapists may use this information to augment their current clinical practice and knowledge and assist them in monitoring a child's everyday vocalizations in natural settings. It will also help therapists predict children's later language development which can inform the type and timing of interventions.
1. Oller DK, Niyogi P, Gray S, Richards JA, Gilkerson J, Xu D, Yapanel U, Warren SF. (2010) Automated vocal analysis of naturalistic recordings from children with autism, language delay, and typical development.Proc Natl Acad Sci U S A. Jul 27;107(30):13354-9. Epub PMID: 20643944

Do You See What I See?
Trial demonstrates that caregivers can effectively teach joint engagement skills

The ability of very young children to engage others and communicate socially using non-verbal cues such as pointing, smiling, or making eye contact is critical to social and language development. Children learn to relate and communicate nonverbally long before they learn to communicate using words. Numerous studies show that children who engage their parent or caregiver in sharing communications such as pointing to things of interest or directing another's attention to objects, learn language faster. These skills, referred to as joint attention skills, are significantly impaired in very young children with autism and therefore have been the targets of early intervention programs.

A lack of reciprocity or joint engagement is often a red flag for parents. Given that children are being diagnosed with autism at much younger ages, there is a need to develop early interventions that target these skills. In this study, researchers asked parents/caregivers rather than clinicians to deliver an intervention aimed at increasing social communication outcomes of young children with autism. Thirty-eight caregivers and their toddlers with autism who were 21-36 months of age were randomly assigned to either the treatment group or a waitlist control group. The study focused on toddlers who had the least amount of language based on previous findings that these children benefit most from the joint engagement intervention.

The 8-week intervention focused on the development of play routines during which the parent/caregiver would actively participate, maintain, and expand upon the child's play activities. The goal was to keep the child engaged on the shared play activity for longer periods of time during which the child's social communication and language behaviors could be facilitated.

The results showed that children in the treatment group developed strong joint attention skills. These gains in joint engagement, joint attention and play were either maintained or improved one year following termination of the intervention. Children in the treatment group spent less time focused solely on objects and significantly more time engaged with parents during play compared to children in the control group.

This is one of the first randomized controlled trials to demonstrate that a relatively brief caregiver-mediated intervention can improve social interaction, joint attention and play skills in toddlers with autism. While the benefits of parent-mediated versus therapist-mediated interventions have not been studied directly, parent-mediated models may prove to be a cost effective way to widely disseminate effective interventions to young children with ASD.

1. Kasari C, Gulsrud AC, Wong C, Kwon S, Locke J. (2010) Randomized controlled caregiver mediated joint engagement intervention for toddlers with autism.J Autism Dev Disord. Sep;40(9):1045-5

Prematurity as a Risk Factor
Longitudinal studies describe developmental trajectories of low birth weight and premature infants

As advances in medicine and discoveries in health sciences have lead to increased survival of infants born prior to 33 gestational weeks, there is a greater interest in understanding the later health and development of these children as they develop. This year, multiple studies reported findings of increased risk of autism in cohorts of infants born prior to 33 weeks or with very low birth weight (less than 3 lbs, 5 ounces). Researchers studied cohorts from across the globe and screened for multiple behavioral outcomes from age 4-14 years of age, including ADHD, autism, conduct disorders, phobias, cognitive delays and emotional problems. These findings expand and complement previous reports using cross sectional designs that have identified low birth weight and gestational age as risk factors for autism.

One set of studies followed a cohort in the United Kingdom. Investigators recruited all babies born prior to 26 weeks who were admitted to the neonatal intensive care unit (NICU). During follow-up at 2.5, 6 and 11 years, they were compared to classmates born at term. About 23 percent of children born preterm had one of the conditions studied; one of the most common conditions was ASD, which was found in 8% of the children born prematurely by age 112. In a follow up report based on questionnaire data3, it was found that extremely preterm children are especially at risk for ASD behaviors and cognitive delay.

In another study4, very low birth weight children of age, the children were reexamined and assessed for autism behaviors, attention and emotional problems. Children with low birth weight were more likely to have behavioral difficulties, including problems with attention and social behavior. Another group examined the behavioral development of children who spent time in the neonatal intensive care unit5 after birth. While the prevalence of ASD in NICU graduates was no different than that in the general population, the researchers found that NICU graduates were compared to those who were small for gestational age. At 14 years who were diagnosed with ASD were more likely to be preterm or have low birth weight. Children who were later diagnosed with ASD show differences in attention as early as four months of age, suggesting an early marker of later development.

What mechanism can explain why and how prematurity or low birth weight is a risk factor for ASD? Given the wide range of symptoms later found in children who are born extremely premature, influences of prematurity on brain development appear to be variable. The neurobiological impact of preterm birth may be part of a larger profile of cognitive, attention and functional impairments. On the other hand, premature birth may also be associated with greater sensitivity to a number of environmental factors.

1. Schendel D and Bhasin TK. (2008) Birth weight and gestational age characteristics of children with autism, including a comparison with other developmental disabilities.Pediatrics, 121: 1155-1164.
2. Johnson S, Hollis C, Kochhar P, Hennessy E, Wolke D and Marlow N (2010) Psychiatric disorders in extremely preterm children: longitudinal finding at age 11 years in the EPICure Study.Journal of the American Academy of Child and Adolecent Psychiatry, 49: 453-463.
3. Johnson S, Hollis C, Kochhar P, Hennessy E, Wolke D and Marlow N (2010) Autism spectrum disorders in extremely preterm children.Journal of Pediatrics, 156: 525-531,
4. Indredavid MS, Torstein V, Evensen KAI, Skranes J,Taradsen G and Brubakk A-M (2010) Perinatal risk and psychiatric outcome in adolescents born preterm with very low birth weight or term small for gestational age.Journal of Developmental and Behavioral Pediatrics, 31: 286-294.
5. Karmel BZ, Gardner JM, Meade LS, Cohen IL, London E, Flory MJ, Lennon EM, Miroshnicknko I, Rabinowitz S, Parab S, Barone A and Harin A (2010) Early medical and Behavioral Characteristics of NICU infants later classified with ASD.Pediatrics, 126: 457-467.

New Evidence for Neuronal Network Imbalance in ASD
A new study links the gene that causes Rett syndrome to reduced levels of the inhibitory neurotransmitter GABA in brain cells

Our understanding of many aspects of ASD biology has come from studying single gene disorders that have a high incidence of autism, such as Fragile X, Tuberous Sclerosis and Rett Syndrome (see also iPSC Top 10 story). Based on these types of studies, a current theory posits that autism is associated with over-excitation in the brain. The proper balance between excitation and inhibition in the brain is critical for normal function. Previous research has revealed that there is often too much of the excitatory neurotransmitter, glutamate, released between communicating neurons, causing overexcitation in local networks.

This November, in the journal Nature, Huda Zoghbi, M.D. and colleagues showed that a dearth of an inhibitory transmitter, GABA, in a new animal model also leads to over-excitability in neuron networks.1 Too little GABA in the network of neurons is somewhat like having faulty breaks in a car. In the mouse model, the over-excitability of the circuit leads to the repetitive behaviors associated with Rett syndrome. Obsessive hand-wringing behavior is a classic symptom of girls with Rett syndrome. In the mouse these symptoms include over-grooming and paw-clasping.

The traditional model for studying Rett syndrome is a mouse that is carrying an ineffective copy of the gene MeCP2. The Zoghbi lab research, led by postdoctoral fellow Hsiao-Tuan Chao, used a twist on this approach. Using molecular tools, the research team removed MeCP2 from specific cell types in the brain, in this case only cells that released GABA. The results were surprising. First, MeCP2 was found in great quantities in neurons that released GABA. Second, MeCP2 was shown to have a previously undiscovered role in producing GABA, as seen by a 30 percent drop in GABA measured when MeCP2 was “knocked-out”. Third, although the knock-out was restricted to only cells containing GABA, these mice mirrored most of the autism-like symptoms observed in girls with Rett syndrome.

The GABA-specific MeCP2 mutation was also made brain-region specific, so only parts of the brain would have the mutation. Although removing MeCP2 from all GABA-producing cells led to the late-stage breathing abnormalities and premature death that is unfortunately common in Rett syndrome, restriction of the MeCP2 knockout to GABA-producing cells in the front of brain resulted only in the types of behavioral symptoms familiar to autism.

The demonstration that MeCP2 is involved in the production of GABA is a new finding with great implications. “These findings reveal for perhaps the first time that subtle impairments in the function of GABA-releasing neurons, from any of a variety of causes, could lead to neuropsychiatric disorders like autism,” said Dr. Chao. Importantly, identification of a biological pathway opens the doors for treatment possibilities and drawing links to treatments that are already in the testing pipeline.

1. Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, Neul JL, Gong S, Lu HC, Heintz N, Ekker M, Rubenstein JL, Noebels JL, Rosenmund C, Zoghbi HY. (2010) Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.Nature. Nov 11;468(7321):263-9.

New Imaging Techniques Shed Light on Autism Speaks
A new set of imaging measures helps characterize brain differences in ASD

Despite several decades of research effort, autism remains a behaviorally-defined disorder without any biological markers. New imaging methods aim to bring us closer to the goal of a biologically-based screening test for ASD.

A study1 from Declan Murphy, Ph.D. and colleagues used magnetic resonance (MR) structural brain imaging in combination with sophisticated machine learning methods designed to classify based on small differences in five different local measures of brain size, such as thickness of the cerebral cortex. In their study of adults with ASD and individuals with ADHD or normal development, this method was found to classify the individuals with ASD in their study with as much as 90 percent accuracy, which is impressive given that the scan only takes 15 minutes.

Although the literature is full of reports of specific brain areas being larger, smaller, more or less active in individuals with autism compared with typically developing peers, this report offers a different message. The researchers did not find, nor do they believe one should expect to find, one thing that distinguishes the brains of those with autism. The reason is that we are learning that there are many different paths that lead to what we behaviorally define as ASD and each of those paths may correspond to distinct differences in the brain.

This report, as well as those of other groups performing similar image-based diagnostics later in the year, garnered considerable media attention. The authors caution that the technology is still far from substituting for traditional diagnostic measures. It is possible that early changes in brain anatomy might serve as subtle markers of risk for ASD, however. Scientists are currently using brain imaging to assess young infants who are at risk for ASD to see if these measures can provide a new method for early detection. Given the speed and availability of scanners, perhaps methods such as these (and others, see voice analysis story) can assist in screening for ASD.

There is also the hope for imaging as a concrete method of measuring therapeutic success. Will behavioral improvements also lead to measureable changes in MR images? Time will tell, but 2010 should be remembered as a year when imaging biomarkers for ASD made their mark.

1. Ecker C, Marquand A, Mourão-Miranda J, Johnston P, Daly EM, Brammer MJ, Maltezos S, Murphy CM, Robertson D, Williams SC, Murphy DG. (2010) Describing the brain in autism in five dimensions--magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. J Neurosci. Aug 11;30(32):10612-23.

Mitochondrial Disorder More Common than Expected in ASD
New findings and methods relating cellular energy production and autism

Last year's Top 10 featured a report on regression in children with both autism and mitochondrial disorder. This year has had its share of mitochondria in the news as well, especially recently with Cecilia Giulivi, Ph.D. and colleagues reporting in the Journal of the American Medical Association (JAMA) a greater incidence of mitochondrial dysfunction in young children with autism.

Mitochondria are the cells' main provider of fuel. With the tens of billions of neurons in the brain, each actively receiving electrical signals and converting them to chemical messages to pass along to neighboring neurons, the brain is a very energetically expensive organ. Although there are hints in previous research that autism is associated with abnormal energy metabolism in autism, studies of mitochondrial dysfunction in autism are still relatively few. One challenge is that the gold standard method of assessing mitochondrial function involves an invasive muscle biopsy. Dr. Giulivi wanted to test whether mitochondrial dysfunction could be tested using a much less invasive method.

Giulivi and colleagues used blood samples from children aged 2-5 years old with autism who were enrolled in the CHARGE study. Mitochondria aren't typically obtained from blood samples because it was believed that there weren't enough to analyze – there are no mitochondria in red blood cells. However the white blood cells, specifically lymphocytes, do have reasonable quantities of mitochondria. Giulivi developed methods for isolating these mitochondria and measuring the function of the enzyme chain that convert nutrients into energy.

The researchers found evidence of mitochondrial dysfunction in the enzyme chain in 8 of the 10 children with autism but none of the typically-developing children. Mitochondrial DNA mutations were also observed in the children with autism. Curious at first blush, the children with autism appeared to have more copies of mitochondrial DNA. This makes sense if each individual mitochondrion is functioning imperfectly and so more are needed to fill the energy demands of the cells.

The advantage of identifying mitochondrial dysfunction is that there are ways to support better function. Through diet, exercise and in some cases, supplements, individuals with mitochondrial dysfunction can improve significantly (see the United Mitochondrial Disease Foundation for more information). We look forward to next year to see how this research develops.

1. Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. (2010) Mitochondrial dysfunction in autism.JAMA. Dec 1;304(21):2389-96.

New Pathways for Autism Genetics
Autism Speaks' Autism Genome Project identifies new genes and pathways involved in ASD

When the Autism Genome Project (AGP), an international autism genetics research consortium, published results from their analysis of a large sample of individuals with autism in June, the occasion attracted a lot of attention from popular media as well as the scientific community. The excitement was due to both the discovery of new genetic causes and biological mechanisms for autism and the promise that these discoveries hold for the development of new diagnostics and treatments.

Co-funded by Autism Speaks with other international public-private funding agencies, the AGP found several new autism risk genes by identifying copy number variants (CNVs), rare tiny insertions and deletions in the genome, which appear to disrupt more genes in individuals with autism than in the general population. Some of these CNVs are considered “highly penetrant” or sufficiently disruptive to cause autism on their own, while others only raise the risk for autism and may interact with other genetic and/or environmental risk factors to cause the disorder. Furthermore, while many CNVs are inherited, some are “de novo” meaning that they are found only in the child but not the parents.

Like other genetic risk factors reported in recent years, some of the new genes, such as SHANK2 and SYNGAP1, work at the synapse, the communication hub between neurons. Others, however, appear to cluster around specific biochemical pathways in the brain, including those involved in cell growth and motility. This novel finding suggests new biological mechanisms that could shed light on how autism develops.

Interestingly, some of the affected genes have also been implicated in intellectual disabilities, furthering the idea previously proposed by other researchers that at least some of genes are shared by different developmental disorders.

The new risk genes also support the idea that autism is caused in part by a number of “rare variants” or genetic changes found in less than one percent of the population. While each of these variants may only account for a small fraction of the cases, collectively they appear to account for a substantial percentage of individuals with ASD.

Taken together, the AGP findings point to new and exciting opportunities to develop clinical solutions for our community. Some doctors have already begun looking for the risk genes identified by the AGP and others as part of their diagnostic assessment of a child with ASD. Identification of the novel biochemical pathways involved in autism increases the chance of finding drugs that target these pathways to help recover pathway function. As part of this important effort, Autism Speaks will be co-sponsoring a research meeting in early 2011 to explore the translation of these genetic discoveries into potential therapeutics.

1. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C. (2010) Functional impact of global rare copy number variation in autism spectrum disorders.Nature. Jul 15;466(7304):368-72.

Researchers Create Neurons from Skin Cells of Individuals with ASD
“Disease in a dish” technology comes to ASD to further understanding of autism biology and screen novel drug treatments

For a decade researchers have heralded the promise of stem cells as the basis of medical breakthroughs-to-come. With the discovery of new stem cell reprogramming techniques in 2006, creation of stem cells taken directly from living people finally became a reality, and scientists all over the world started the race to create stem cells from individuals with a variety of specific conditions. For autism, stem cells made their mark in October 2010 when scientists in California generated stem cells (called inducible pluripotent stem cells, or iPSCs) from skin samples of people with a condition associated with autism spectrum disorder, Rett syndrome. The stem cells offered some of the first clues to what autism may look like at a cellular level, and provide a remarkable new way to test autism treatments.

Stem cells are primitive cells that serve as the supply source for mature cells in our body. Stem cells are able to do this because of two special properties – they can self-renew, meaning they can divide over and over to create more stem cells just like themselves, and they are multi-potential, meaning that the daughter cells they give birth to can adopt different fates depending on the signals they receive. For the public, stem cells are perhaps best known as a means to directly supply replacements for cells lost due to disease, such as in Parkinson's or spinal cord injury. However, stem cells are having perhaps a bigger impact not by becoming the actual treatment itself, but by providing researchers with the opportunity to study unlimited quantities of cells associated with different conditions. Thus, stem cells provide an invaluable resource by creating new laboratory models, and for screening drugs. For example, such “diseases in a dish” have already been made using stem cells from patients with Lou Gerhig's disease and Spinal Muscular Atrophy.

Researchers from Salk Institute and UCSD have now published their initial successes creating, studying, and treating iPSC-derived neurons from patients with Rett syndrome. The investigators, led by Alysson Muotri, Ph.D., found striking differences in the iPSC-Rett neurons. They had smaller cell bodies and fewer points of communication, or synapses, between them. The neurons also functioned differently, showing fewer spontaneous bursts of activity.

Carol Marchetto, Ph.D., the paper's first author, took the power of iPSCs further. She applied two drugs that compensated in different ways for the effects of the mutated gene, MeCP2, that causes Rett syndrome. Application of insulin-like growth factor 1 (IGF1) has previously been shown to delay the onset and even reverse the neurological symptoms in a Rett syndrome animal model. The addition of IGF1 to Rett-derived neurons resulted in more synapses. Similarly, a type of antibiotic (Gentamicin) causes cellular error-correction mechanisms to effectively turn a blind eye to mutations when creating proteins. By altering the effects of mutations that would normally have stopped the creation of MeCP2, this drug also produces more synapses in the Rett-derived neurons.

The stem cell field is in its infancy, but with new techniques making this complicated process easier and easier, stem cell researchers all over the world are beginning to model autism and its related disorders. In 2010 scientists also published initial stem cells findings on Fragile X, Angelman and Prader-Willi syndrome, all conditions that have autism as a feature. The significance of having these stem cells is not just that we are now closer to revealing the biological mysteries of autism but, as the California researchers showed, that the stem cells can directly be used as a way to screen for therapeutics based on the specific deficit found in a person's cells. This opens the future to design of individually-tailored treatments and makes personalized medicine for autism no longer only a dream.

1. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR. (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.Cell.Nov 12;143(4):527-39.PMID: 21074045
2. Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. (2010) Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells.Cell Stem Cell. May 7;6(5):407-11. . PMID: 20452313
3. Chamberlain SJ, Chen PF, Ng KY, Bourgois-Rocha F, Lemtiri-Chlieh F, Levine ES, Lalande M. (2010) Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes.Proc Natl Acad Sci U S A.Oct 12;107(41):17668-73. Epub 2010 Sep 27.PMID: 20876107

A Closer Look at Early Autism Symptoms That Emerge in Infancy
A groundbreaking study examines the earliest signs of autism in siblings of children on the spectrum

For the first time, researchers have been able to directly observe how the earliest signs of autism emerge in a prospective study of infants who were later diagnosed with autism. Before this type of study, our understanding of the early symptoms of autism relied either on parents' recollection or home videotapes. Many parents have expressed concerns about their infant well before a formal diagnosis could be made. But, it has been difficult to systematically study what symptoms show up during the infant period.

Sally Ozonoff, Ph.D., and her colleagues at UC Davis have been following a large group of infants who are at risk for autism because they have an older sibling with autism, making careful observations at 6, 12, 18, 24, and 36 months of age. This report focuses on a subgroup of 25 high risk infants who later developed autism who were compared to 25 low risk infants. Dr. Ozonoff and colleagues found that infants who later developed autism did not show any observable symptoms at 6 months of age. At this early age, the infants were making eye contact, vocalizing and smiling at others. Between 6 and 12 months of age, however, these infants gradually lost their social skills. By 12 months of age, they were clearly different than the low risk infants who continued to gain in their language and social skills. Although this gradual loss of social skills can be viewed as a type of regression, most parents did not report that their child had regressed, perhaps because the loss of skills was so gradual. The researchers also assessed whether the infants lost skills in other areas, such as visual skills. They found that the loss was specific to the area of social communication.

This study provides us with a closer look at the first observable symptoms of early onset autism. The results suggest that it should be possible to detect autism symptoms before one year of age, at least for children with early onset autism. Screening tools should focus on the social communication skills that infants display between 6-12 months, such as looking, vocalizing, and smiling at others. Dr. Ozonoff noted that it might be necessary to screen infants several times because the loss of skills can be very gradual. By paying attention to these early social communication skills during a well-baby check-up, pediatricians may someday be able to refer infants at risk for autism for interventions that can help promote the development of these skills. Autism Speaks is currently funding several clinical trials aimed at developing interventions that can be used with infants and toddlers with autism.

1.Ozonoff S,Iosif AM,Baguio F,Cook IC,Hill MM,Hutman T,Rogers SJ,Rozga A,Sangha S, Sigman M, Steinfeld MB, Young GS. (2010) A prospective study of the emergence of early behavioral signs of autism.JAm Acad Child Adolesc Psychiatry. Mar;49(3):256-66.e1-2.

Gastrointestinal Concerns Addressed with New Clinical Guidelines
New guidelines help parents advocate for their children with GI problems

Gastrointestinal (GI) problems are a commonly expressed concern of parents of children with ASD, but there remains a significant need for clinical guidance and research in this area. In January 2010, a consensus statement and recommendations for the evaluation, diagnosis, and treatment of GI disorders in children with ASD were published in Pediatrics.These recommendations are an important step in advancing physician awareness of the unique challenges in the medical management of children with autism and will be another step towards the development of evidence-based guidelines that will standardize care for all children with ASD. The reports highlighted the crucial need for information to guide care, and emphasized the importance of fostering more research in this area to support the development of these guidelines.

The consensus statement highlights several important themes, the first emphasizing that GI problems are a genuine concern in the ASD population and that these disorders exacerbate or contribute to problem behaviors. The need for awareness of how GI problems manifest in children with autism and the potential for accompanying nutritional complications and impaired quality of life were also emphasized. In the second paper, the authors make consensus recommendations providing guidance for current general pediatric standards of care that can and should be used by those treating children with ASD.

Autism Speaks is already engaged in the next step which is to move beyond these consensus-based recommendations to develop evidence-based clinical guidelines through the work of the members of its Autism Treatment Network (, a program addressing co-morbid medical conditions in the ASD population. George Fuchs, M.D., a co-author on the two papers and chair of Autism Speaks' ATN GI Committee remarked, “The recommendations provide important guidance for the clinician to adapt the current practices of care (for abdominal pain, chronic constipation and gastroesophageal reflux) for the child with autism. The recommendations complement the ATN's on-going work to develop evidence-based, ASD-specific guidelines. The ATN is currently piloting newly created guidelines and monitoring their effectiveness. We anticipate this data will contribute to an evidence-based foundation to support best practices for GI problems in ASD.”

1. Buie T, Fuchs GJ 3rd, Furuta GT, Kooros K, Levy J, Lewis JD, Wershil BK, Winter H. Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. (2010)Pediatrics. Jan;125 Suppl 1:S19-29.
2. Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. (2010) Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. Jan;125 Suppl 1:S1-18

About Autism
Autism is a complex neurobiological disorder that inhibits a person's ability to communicate and develop social relationships, and is often accompanied by behavioral challenges. Autism spectrum disorders are diagnosed in one in 110 children in the United States, affecting four times as many boys as girls. The prevalence of autism increased 57 percent from 2002 to 2006. The Centers for Disease Control and Prevention has called autism a national public health concern whose cause and cure remain unknown.

About Autism Speaks
Autism Speaks is North America's largest autism science and advocacy organization. Since its inception in 2005, Autism Speaks has made enormous strides, committing over $142.5 million to research through 2014 and developing innovative new resources for families. The organization is dedicated to funding research into the causes, prevention, treatments and a cure for autism; increasing awareness of autism spectrum disorders; and advocating for the needs of individuals with autism and their families. In addition to funding research, Autism Speaks has created resources and programs including the Autism Speaks Autism Treatment Network, Autism Speaks' Autism Genetic Resource Exchange and several other scientific and clinical programs. Notable awareness initiatives include the establishment of the annual United Nations-sanctioned World Autism Awareness Day on April 2, which Autism Speaks celebrates through its Light it Up Blue initiative. Also, Autism Speaks award-winning “Learn the Signs” campaign with the Ad Council has received over $258 million in donated media. Autism Speaks' family resources include the Autism Video Glossary, a 100 Day Kit for newly-diagnosed families, a School Community Tool Kit and a community grant program. Autism Speaks has played a critical role in securing federal legislation to advance the government's response to autism, and has successfully advocated for insurance reform to cover behavioral treatments in 23 states thus far, with bills pending in an additional 14 states. Each year Walk Now for Autism Speaks events are held in more than 80 cities across North America. To learn more about Autism Speaks, please visit

About the Co-Founders
Autism Speaks was founded in February 2005 by Suzanne and Bob Wright, the grandparents of a child with autism. Bob Wright is Senior Advisor at Lee Equity Partners, Chairman and CEO of the Palm Beach Civic Association and served as vice chairman, General Electric, and chief executive officer of NBC and NBC Universal for more than twenty years. He also serves on the boards of the Polo Ralph Lauren Corporation, RAND Corporation and the New York Presbyterian Hospital. Suzanne Wright has an extensive history of active involvement in community and philanthropic endeavors, mostly directed toward helping children. She is a Trustee Emeritus of Sarah Lawrence College, her alma mater. Suzanne has received numerous awards, such as the CHILD Magazine Children's Champions Award, Luella Bennack Volunteer Award, Spirit of Achievement award by the Albert Einstein College of Medicine's National Women's Divisionand The Women of Vision Award from the Weizmann Institute of Science. In 2008, the Wrights were named to the Time 100 Heroes and Pioneers category, a list of the most influential people in the world, for their commitment to global autism advocacy. They have also received numerous awards such as the first ever Double Helix Award for Corporate Leadership, NYU Child Advocacy Award, Castle Connolly National Health Leadership Award and The American Ireland Fund Humanitarian Award. In May of 2010 they received Honorary Doctor of Humane Letters Degrees from St. John's University in Queens and delivered the commencement address as the first married couple to be bestowed such an honor.
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