On a day to day basis, I can get so immersed in the mechanics, data and details of what I do that I sometimes forget to step back and see the bigger picture: The tremendous value of the research information systems that Autism Speaks has created within its Autism Genetic Resource Exchange (AGRE).
I am feeling particularly sensitive to this “big picture” with this week’s announcement of the historic addition of AGRE information to the National Database for Autism Research (NDAR), which is supported and maintained by the National Institutes of Health.
I’m reminded that the goal of all my work is to increase the availability and usefulness of the vital information that we collect—information that can advance the scientific understanding of autism and speed the development of better treatments.
I promise to spare you the technical details. Suffice it to say, our role is to take the anonymous information (de-identified data) we gather from our participating families and put it in an easy-to-use format that autism researchers can use to increase the power and accuracy of their scientific findings and insights.
In joining our data with NDAR’s, we are making more comprehensive data available to the broader scientific community and also linking data collected on participants within AGRE with additional data on the same participants across a variety of other research studies (all anonymous). This is adding significantly to the autism field’s body of scientific knowledge. And this is our obligation to our families: To maximize their contributions and make sure their de-identified data will always be available to qualified scientists who are working to improve the lives of those who struggle with autism. We take pride in providing researchers with the most comprehensive and highest quality of data possible, so that they can do what they do best: science.
Special thanks go to Reinis Berzins, our AGRE data projects coordinator, whose position was made possible by the $1 million National Institutes of Health grant we received to integrate the AGRE and NDAR databases. To learn more about AGRE, please visit its website. To learn more about the AGRE-NDAR federation, please see this week’s related news item.
Read more science news and perspective on the Science Page.
Thank you to all our supporters, whose funding made the following discoveries possible in November. Explore more of the studies we’re funding with our Grant Search.
* Empathic Responding in Toddlers at Risk for an Autism Spectrum Disorder. McDonald NM and Messinger DS. J Autism Dev Disord. 2011 Nov 1. [Epub ahead of print]
* Association of GTF2i in the Williams-Beuren Syndrome Critical Region with Autism Spectrum Disorders. Malenfant P, Liu X, Hudson ML, Qiao Y, Hrynchak M, Riendeau N, Hildebrand MJ, Cohen IL, Chudley AE, Forster-Gibson C, Mickelson EC, Rajcan-Separovic E, Lewis ME, Holden JJ. J Autism Dev Disord. 2011 Nov 3. [Epub ahead of print]
* An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males. Chung RH, Ma D, Wang K, Hedges DJ, Jaworski JM, Gilbert JR, Cuccaro ML, Wright HH, Abramson RK, Konidari I, Whitehead PL, Schellenberg GD, Hakonarson H, Haines JL, Pericak-Vance MA, Martin ER. Mol Autism. 2011 Nov 4;2(1):18.
* Epigenetic Signatures of Autism: Trimethylated H3K4 Landscapes in Prefrontal Neurons. Shulha HP, Cheung I, Whittle C, Wang J, Virgil D, Lin CL, Guo Y, Lessard A, Akbarian S, Weng Z. Arch Gen Psychiatry. 2011 Nov 7. [Epub ahead of print]
* Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13. Tobiasova Z, Lingen KH, Scahill L, Leckman JF, Zhang Y, Chae W, McCracken JT, McDougle CJ, Vitiello B, Tierney E, Aman MG, Arnold LE, Katsovich L, Hoekstra PJ, Volkmar F, Bothwell AL, Kawikova I. J Child Adolesc Psychopharmacol. 2011 Nov 9. [Epub ahead of print]
* Neuron Number and Size in Prefrontal Cortex of Children with Autism. Courchesne E, Mouton PR, Calhoun ME, et al. JAMA.2011;306(18):2001-10.
* Behavioral and Physiological Responses to Child-Directed Speech of Children with Autism Spectrum Disorders or Typical Development. Watson LR, Roberts JE, Baranek GT, Mandulak KC, and Dalton JC. J Autism Dev Disord. 2011 Nov 10. [Epub ahead of print]
* Sex differences in repetitive stereotyped behaviors in autism: Implications for genetic liability. Szatmari P, Liu XQ, Goldberg J, Zwaigenbaum L, Paterson AD, Woodbury-Smith M, Georgiades S, Duku E, Thompson A. Am J Med Genet B Neuropsychiatr Genet. 2011 Nov 16. [Epub ahead of print]
* Diagnostic Yield of Chromosomal Microarray Analysis in an Autism Primary Care Practice: Which Guidelines to Implement? McGrew SG, Peters BR, Crittendon JA and Veenstra-Vanderweele J. J Autism Dev Disord. 2011 Nov 17. [Epub ahead of print]
* Participation in Social Activities among Adolescents with an Autism Spectrum Disorder. Shattuck PT, Orsmond GI, Wagner M, Cooper BP. PLoS One. 2011;6(11):e27176. Epub 2011 Nov 14.
* Exploring the Relationship Between Autism Spectrum Disorder and Epilepsy Using Latent Class Cluster Analysis. Cuccaro ML, Tuchman RF, Hamilton KL, Wright HH, Abramson RK, Haines JL, Gilbert JR, Pericak-Vance M. J Autism Dev Disord. 2011 Nov 22. [Epub ahead of print]
* Normal Rates of Neuroradiological Findings in Children with High Functioning Autism. Vasa RA, Ranta M, Huisman TA, Pinto PS, Tillman RM, Mostofsky SH. J Autism Dev Disord. 2011 Nov 22. [Epub ahead of print]
* QTL replication and targeted association highlight the nerve growth factor gene for nonverbal communication deficits in autism spectrum disorders. Lu AT, Yoon J, Geschwind DH, Cantor RM. Mol Psychiatry. 2011 Nov 22. [Epub ahead of print]
* Very Little High-quality Evidence to Support Most Medications for Children with Autism Spectrum Disorders. Coury D. J Pediatr. 2011 Nov;159(5):872-3.
This blog post is by Richard Fauth
It didn’t come from me. I have to admit I could never pull it off like he does. It must be because he’s half-French (his mother’s half.) Last Sunday, we had a cook-out with a family of friends at Fort Wilderness in Disney World. My 8-year-old son Lucas was at it again. Smooth. It didn’t take him long to catch the eye of a college-age girl. He took her shoes off. Before long he was riding around the campground in a golf cart with the other kids. She was driving; he was riding shot-gun. That’s my boy. The cutest little boy on the planet. Although he can say only a few words, I knew he couldn’t be happier.
Lucas has autism and some researchers find him interesting. A sample of Lucas’ DNA was tested by a commercial lab a few years ago for three autism suspect genes. Sequencing tests for the genes (CDKL5, Cntnap2 and Shank 3) were among the first to be performed. The results are what researchers find interesting — unusual variants or mutations in two of the genes-Shank3 and Cntnap2. These results also changed our lives — we left a world where things were increasingly desperate and entered a world of new found hope. Some now say Lucas may be one of the most researched children with autism in the country.
Like many parents, Marie and I spend a lot of effort trying to get the best for our child. Like many kids, Lucas’ day is filled with “activities,” although if he could speak well enough, I think he would call it “work.” He puts in a tough week – long hours of special education, speech therapy, occupational therapy, and applied behavioral therapy. But he also has some fun — “special kids” dance class on Saturday and some gym classes.
As I write this, skin cells from Lucas, Marie and me are being converted to Pluripotent stem cells at a laboratory at Stanford University. From these stem cells, the researchers will grow neuronal tissue. The research is aimed at developing drugs to improve the outcomes of many children. Another study, a paper concerning a variant in Lucas’ Shank3 gene, has already been published. We have been invited to join another study and there is other interest-full Exomic sequencing of autism suspect genes in Lucas.
Lucas has been to Boston Children’s Hospital-Harvard, Stanford University, Mt. Sinai Hospital in New York, and the Dan Marino Center in Miami. We have visited the Kennedy Krieger Center in Baltimore. Every time I see one of those “my kid made the honor roll at…” bumper stickers, I want to put a sticker on the back of my car listing all the places my kid has been to, followed by “so there!”
He’s my boy and I’m proud of him. Daddy knows; I tell him so when he gets real frustrated because he can’t speak. As hard as it is on Marie and me, it is incredibly difficult for him. We fear that this will not get any easier for him. What we know is that without effective research, it likely won’t.
Lucas can swim in our pool here in Orlando. He also loves his trampoline. The “It’s a small world after all” ride at Disney World is now second on Lucas’ list of cool things to do. First is going to the beach -especially during a “Surfers for Autism” event. These are closely followed by long airplane flights and jumping on hotel beds. The last time we went for a weekend at the beach, he threw a fit when we left-he’d just as soon hang out there indefinitely. I know the feeling.
But it is another feeling that stays with me most days. It is the feeling that when the day comes when I leave this world, I will have not done enough to make the difference needed for Lucas. This has got to be every parent’s worst nightmare — failing to be a good enough advocate. At 52, I already believe that I will never retire. I could spend my time fighting for insurance reform so that Marie and I wouldn’t have to come up with $25,000 to $35,000 each year for Lucas’ therapies and someday I could retire. Or I can spend more time doing what I can to advocate for the bigger agenda: finding effective therapeutics for children with autism.
So Marie and I pour over autism research. As part of the ongoing research concerning Shank 3 mutations, I am a proud member of the Phelan McDermid Syndrome (PMS) Research Support committee along with a group of very smart parents fighting with me to find help for our kids. Lucas does not have the deletion in chromosome 22 that causes PMS, but rather mutations in the Shank3 gene which researchers believe may cause autism.
I only wish that more parents would push for research into the dozens, if not hundreds, of autism suspect genes and the pathways that variants in these genes disrupt. I also have hopes. Hopes that more sequencing will be available and affordable in the near future. That Pluripotent stem cell, brain imaging and genetics research will answer many of the questions needed to move into effective drugs. And that research concerning speech, occupational and ABA and other psychological therapies yields improved outcomes for our children.
After watching a WWII movie last Memorial Day, I began pondering the notion of “the greatest generation.” I also recently read The Immortal Life of Henrietta Lacks about He La cells and the Herculean effort our country undertook to beat polio. I believe it is this generation’s challenge to beat the developmental disability that is autism. We are on the cusp of major findings into the causes and potential treatments for autism. Trials are underway using experimental drugs to combat Fragile X and Rett syndromes. Research is implicating mutations in many of the same genes affected in other disorders with disrupted chromosomes, disorders in which classic autism exists- such as PMS. Common pathways are emerging in the literature. For a segment of the population, we now know what causes autism. The first studies concerning children and multiple autism suspect gene mutations have been published.
It matters. What we know, where we go, how we get there. That is the sentiment on the faces of parents we meet involved in research and support for their children on the spectrum. Parents who would move heaven and earth to help their kids. A hope that comes with research.
This month has been a tremendously exciting time in autism research, as our blog posts make clear. Naively, I’ve been waiting for a pause in the torrent of news to introduce myself. That’s not looking likely, so allow me to shoehorn a quick intro—and a couple questions for you.
Three weeks ago, I stepped into the newly created position of Autism Speaks’ director of science communications. It’s now my privilege to suds and squeegee your window onto the science that donor dollars are funding. I’ll also be enlisting our science staff to answer your questions and generally provide perspective on some of the splashy—and sometimes confusing—headlines in the national news.
By background, I’m a science journalist and medical writer. For the last 20 years, I’ve been a regular contributor to national magazines such as Discover, Popular Science, Parents, Parenting, and Prevention. I’ve also written a few science books for the general reader, the most recent being Good Germs, Bad Germs.
The science staff at Autism Speaks has always been passionate about communicating with families affected by autism and with everyone who cares about enhancing the lives of the remarkable individuals on the spectrum. I’m here to facilitate their conversation with you—in both directions.
Perhaps you’re a volunteer and want resources that can help you explain the nature and importance of the research we fund. Perhaps you have a child affected by autism and would consider participating in research. Perhaps you are a parent who is looking forward to answers and new treatment approaches that will help your child. Or perhaps you are a high-functioning teenager, college student, or other adult on the spectrum and want to know more about studies that relate to you (the link goes to just one example).
In whatever way you’re comfortable, we want to involve you in our scientific mission: To improve the lives of all who struggle with autism. To that end, I’d love your input on some of the new avenues of communication we’re considering. Would you please take a moment to answer our two-question survey? Please feel free to provide additional feedback in the comments section. Thanks!
A new report was released yesterday in the journal Pediatrics that questions the value of uniform early screening for autism spectrum disorders. The premise behind the report titled, “Early Autism Detection: Are We Ready for Routine Screening?” was a desire to evaluate the usefulness of universal screening for infants at 18 to 24 months of age given what is known about the quality of screening tools, the availability of effective treatments, and other considerations.
The authors argue that there have not been enough quality studies comparing screening tools. The availability of effective treatments for those who screened positive is also far from wide or uniform causing the authors to question the value of screening overall.
Autism Speaks remains in support of American Academy of Pediatrics recommendation that all infants be screened for autism spectrum disorders.
The sense of urgency of our mission to create a world in which suffering because of autism no longer exists demands identification and intervention as early as possible, where we do, in fact, have data for the effectiveness for intervention. Dr. Geraldine Dawson, chief science officer of Autism Speaks says, “Early intervention has been shown to result in significant increases in cognitive and language abilities and adaptive behavior, allowing children the best chance for a positive outcome.
Instead of closing the door to an opportunity to guide the development of an infant who is headed toward struggles with an atypical development, we must create new opportunities for those infants to thrive. Indeed, the path to obtaining effective treatments that target the unique needs of your child is still shadowy, but it is something to which are bringing light together. Autism Speaks supports research on effective early screening methods as well as finding best ways to deliver interventions that were shown to be effective to all those who need them today.
This is a guest post by Shelley Hendrix, the Director of State Based Advocacy at Autism Speaks.
The military has a weapon in the war on autism that few people know about even in our own community – a Congressionally Directed Medical Research Program specifically focused on research of previously overlooked medical issues, including autism spectrum disorder.
As a taxpayer, you contribute your two cents to this program – literally – every year.
The Department of Defense Autism Research Program (ARP) was established in 2007 after parents lobbied Congress for years. Lucky enough to be selected as a stakeholder, I participated in shaping the vision and mission of the program in March 2007.The program has a two-tiered review process with proposal evaluation by both a Scientific Review Panel (SRP), which reviews scientific method and validity,and Integration Panel (IP), which primarily focuses on programmatic impact to the community and issues final recommendations for funding projects. My service on the IP has allowed me to be intrinsically involved in funding scientific proposals for projects ranging from those designed to gather preliminary data that may lead to new breakthroughs one day up to complex clinical trials for new treatments or therapy modalities.
Since its inception, ASDRP has funded 66 projects investing $31.9 million in autism research.
What makes this program unique is my ability to contribute my two cents in other ways. In this program, consumers participate throughout the entire process – shaping the program and reviewing the scientific proposals with an equal, respected voice regarding innovation and impact. More importantly to me, consumers fully participate in distribution of funds – advocating expenditure in areas the community wants to be researched – now. Furthermore, if the SRP that a member of the IP believes has promise of significant impact, an IP member can rescue and champion it.
While science keeps plodding along trying to determine the etiology of autism, many parents simply want to find basic answers the quality of our children’s lives now by addressing their behavioral and physical health gastrointestinal, sleep and seizure issues can change the whole family’s life.
Comprised of scientists, clinicians and consumers from a variety of backgrounds, the integration panel has a unique opportunity for candid, civil conversation about the research direction of this program. Everyone has learned to appreciate different perspectives. For example, robotic technology is cool. But most parents don’t want precious research dollars expended on robots to work with our children – at least not while there are still humans around.
The main thing I’ve learned on this panel is that the march of scientific progress not only requires significant money – it also takes a lot of time.
On April 7, 2000, I attended a meeting at the National Institutes of Health with around 250 parents – most had very young children. Fifteen minutes into the presentation, a brave mom stood asking when we could expect some answers. The speaker proudly announced from the podium that we could expect some good answers in 25-30 years.
All 250 of us got up and walked out of the meeting. I walked out because my son Liam was four at the time. The fact that they would not have answers for him until he was 34 seemed ridiculous. They didn’t need to waste time telling me what autism was. They needed to get back to work.
Eleven years later, after serving on the DOD panel, now I understand what she meant. Doesn’t make it easier but now I know firsthand the grant funding process takes years. The actual research takes years after that and then potentially waits even longer for acceptance for publication.
Fall of 2009 – $7.1 Million allocated to the ARP by United States Congress.
December, 2009 – IP meets to review vision and mission of program, research area focus and funding mechanisms.
February, 2010 – Program announcements and requests for proposals posted.
Late April, 2010 – Pre-proposals received from investigators seeking funding.
Late May, 2010 – Pre-proposals screened by IP determining invitees for full proposal submission.
June, 2010 – Invitations for full grant submission mailed.
July, 2010 – Full grant proposals received, prepared by program staff for review by SRP.
September, 2010 – SRP meets to review grant applications.
Late October, 2010 – Program staff organizes and prepares SRP reviews for IP
November 30, 2010 – IP approves $7.1 Million in funding on accepted grant proposals.
January, 2011 – Grant recipients are notified of award and must advise program staff if they accept funding or another source was found. If recipients turn down grants, alternates are contacted in rank order for funding opportunities so every dollar is effectively spent.
February, 2011 – All money is invested. Grant recipients must then demonstrate that approval at their institutional levels to work with human subjects or on human tissues.
September, 2011 – Grantees are anticipated to receive their first funding – funding that was first allocated in 2009.
September 20** - **Wait two, three or four years for the research projects to conclude and another couple for researchers to publish their findings in a paper and it’s easy to see why the process begun on that cold wintery day in Annapolis in December, 2009 might not finish until December 2015, or beyond.
As frustrating as this glacial pace is to parents watching their children suffer day in and day out, just because you cannot see it does not mean research isn’t being done. It does not mean that researchers are not working every day to validate treatments and therapies that have come from your complaints or ideas you developed in your own homes.
I am very proud of the science that the ARP has funded. We have stayed true to areas of research initial stakeholders expressed interest in 76% of the time. Only 12% of funding approved is for scientific proposals replicated in other research programs and the remaining 12% of the funded proposals are highlynovel ideas that are not currently funded by governmental, private or non-profit agencies.
The CDMRP has a number of other research programs in it that have not only provided the world with cutting edge research but have grown exponentially since their inception. For example, Congress appropriates over $100 Million annually to the Breast Cancer Research program.
Congress appropriated another $6.4 Million to the ARP in April 2011. As a community, we could grow that figure for this innovative program if we just act. Learn more about the ARP and register at Autism Votes so you can be first to contact your Congressman and Senator to let them know we want their support to increase funding next year.
In honor of Autism Awareness month, the National Institutes of Health in conjunction with the Department of Health and Human Services held an hour-long lecture and live videocast with two seasoned autism researchers. The talk series was titled “Advances in Treatment Research” and addressed the current state of treatment research in autism including promising new areas and the barriers to getting to effective treatments faster.
Susan Swedo, M.D., a board-certified pediatrician and the Chief of the Pediatrics & Developmental Neuropsychiatry Branch at the National Institute of Mental Health (NIMH), spoke about empirically-supported treatment options in autism, including behavioral and medical treatments. She noted that methods of behavioral intervention have been the most studied. A recent review published in Pediatrics highlighted the positive effects demonstrated in randomized controlled trials of early intervention, including the UCLA Lovass model and the Early Start Denver model of early intervention.
For medical interventions aimed at addressing core symptoms of ASD, such as social and communication impairments, the challenge of evaluating treatments has been greater. Objectively measuring improvements in social and communication is challenging because these impairments differ widely across individuals with ASD. For example, for some the difficulty may be establishing eye contact whereas for others it might be learning how to carry on a conversation. Thus, defining what makes a treatment successful has been surprisingly elusive. For medical conditions where someone became acutely ill, a return to that individual’s former health status would be considered a success. However, autism spectrum disorders are developmental in nature, and difficulties in meeting milestones and acquiring new information about the world tend to compound. For these reasons, it is not clear what the “baseline” is or could be for each individual and that makes the definition of success less clear-cut. This is an even greater concern when considering the costs of treatment, including monetary and potential side effects. For an intervention with a high probability of unpleasant side effects, the likelihood of substantial gain in function must be greater than for an intervention with little risk of negative effects.
Secondly, there appears to be a surprisingly strong placebo effect in autism studies. For some individuals, the psychological effect of receiving “treatment”—even if it is not an active substance– is beneficial in some way. For this reason, small and uncontrolled trials of interventions can be misleading. Large, randomized, controlled trials are considered to be the gold standard method for evaluating effective treatments. Another challenge is that, given that ASD is not one condition but a group of different conditions, what will work for one person may not work for another. When individuals are studied in groups, such as in clinical trials, it might obscure the positive effects of a treatment for a small subgroup of people with ASD.
Dr. Swedo offered the historical example of secretin as a case-in-point. Secretin is a hormone that was claimed to be a successful treatment for autism in many “open label” (ie. uncontrolled) trials. The hormone was both very expensive and difficult to administer. When placebo-controlled trials were completed, it was clear that there weren’t beneficial effect of the drug, but valuable treatment time and dollars were spent on something ineffective in the interim.
Dr. Swedo collaborates with Autism Speaks’ Autism Treatment Network, a group of 17 hospitals offering a comprehensive model of medical care for children on the spectrum. The well-organized network of sites offers an excellent platform for studies of medical effectiveness where the children’s medical needs are well-attended and followed over time.
Dr. Swedo’s talk ended by discussing some new data from her research group at NIMH showing that the sleep EEG patterns of children with autism are different in a surprising way. Young children with autism in her study spend much less time in rapid eye movement (REM) sleep and much greater time in slow wave sleep instead. This is an interesting finding because REM sleep has been hypothesized as important for consolidating memories made during waking hours. Dr. Swedo’s group is currently engaged in the beginning phases of a study using a low dose of Aricept, a drug indicated for dementia associated with Alzheimer’s disease that has the side effect of increasing REM sleep. Autism Speaks is currently funding a study that is examining the relationship between REM sleep and other aspects of sleep and memory in children with ASD. We look forward to hearing the results as they emerge.
Rebecca Landa, Ph.D., CCC-SLP, is an Associate Professor of Psychiatry and Johns Hopkins School of Medicine and Director of the Center for Autism and Related Disorders and of the REACH research program at the Kennedy Krieger Institute. Dr. Landa explores the early signs and interventions for autism during the infant-toddler period.
Dr. Landa views early intervention as “an investment of a lifetime”, because it is during this early time that children set expectations and learn what they are capable of, and the dynamic of the parent-child relationship is established. Her objective in all interventions is to “thwart the spiraling effects” of developmental disorders by improving functioning as quickly as possible.
“I like to think of intervention experience as nourishment for the brain”, says Dr. Landa. New experiences help young children learn how to functionally interact with the world. As young children, the sensory and motor abilities are primary and help set up more complex cognitive and social skills. A good example is in the ‘sticky mittens’ Dr. Amy Needham uses to help young infants learn to grasp. With the special mittens, the young infants had success at a motor skill that they could not previously perform, and this provided a scaffold for building other behaviors. Dr. Landa’s interventions are influenced by the perspective that the mind develops in a manner compelled by the physical abilities and actions of the body.
Dr. Landa also described a randomized controlled behavioral intervention for 16 month old children who have autism or were at high risk for developing autism. Some of the children were randomized into an intensive parent education class to help the parents have more effective interactions with their infants. Other children were enrolled in a full experimental treatment group, involving a classroom-based gathering of one year olds and their parents twice a week. In the experimental group parents learn to observe and implement strategies for engaging their children socially, with toys, and in adaptive routines that help parents generalize to the home through weekly home visits. The children in the experimental group made substantial improvements in their gaze behavior, spending more time engaged in the sort of joint attention interactions that precede more complex social interactions. Meeting these early milestones offer the scaffold for the development of later and more complex social and communicative behaviors.
In addition to their prepared talks, both investigators answered questions from the live audience. The videocast will be archived and available for viewing in the next few days.
On Monday April 11th Suzanne and Bob Wright, Founders of Autism Speaks, were interviewed by MSNBC’s Andrea Mitchell in recognition of April as the nation’s month for autism awareness. Key points discussed – funding for research and adults with autism.
The Science Webinar and Podcast Series is a new service from Autism Speaks to help keep our community informed about the latest in autism research. Each month we will feature a leading expert to share with us the exciting progress being made and what it means for individuals and families affected by autism. Our goal is to help our community better understand all the new and exciting science being supported by Autism Speaks and other funders. We plan to be comprehensive in our coverage, including everything from genetics and environmental sciences to medical care and clinical trials. Occasionally, we will also feature special topics, like awareness and family support, that while not part of the Autism Speaks science program, are informed by our research and development efforts.
We are very pleased that our inaugural episode of the Autism Speaks Science Webinar and Podcast Series features Autism Speaks’ Chief Science Officer, Dr. Geri Dawson. Dr. Dawson will share with us two new exciting science initiatives at Autism Speaks aimed to deliver better medical care and develop novel treatments for our community.
Please find the webinar video below this post, or you may access the audio-only podcast here:
Guest Blogger Geraldine Bliss is the Chair of the Research Support Committee for the Phelan-McDermid Syndrome Foundation.
Six years ago, my son, Charles, was diagnosed with Phelan-McDermid Syndrome (PMS), a rare genetic condition caused by damage to chromosome 22 (22q13). Charles has a chromosome break in the middle of the SHANK3 gene, which codes for the crucial post-synaptic protein, Shank3, mutations of which cause autism. Charles has a rather small deletion by PMS standards, and he was one of the first patients to be diagnosed with PMS through chromosomal microarray.
Once we learned the diagnosis, our family quickly connected with the Phelan-McDermid Syndrome Foundation (PMSF), where we met, both on-line and in person, other families facing the same challenges. Just as in the larger autism community, some individuals with PMS were “just like Charles,” while others were very different. The foundation members were quick to embrace us and make us feel like extended family. Through PMSF’s biennial conference, regional get-togethers, newsletters, family discussion group, and social networking, our 600+ families are able to stay connected and support each other.
PMSF has grown quickly, but our membership numbers reflect only the very tip of the PMS iceberg. In the U.S. alone, we estimate there are about 8,000 children with PMS. Many of these children have never been tested with a chromosomal microarray (the most common test for PMS), either because their doctors have not referred them or because the cost is not covered by their health plans.
Charles is now 12 years old. Just before his 9th birthday, he started having seizures. As his seizures spiraled out of control, and we began to exhaust one treatment option after another, I promised Charles to do whatever I could to help him get better. I became the chair of the PMSF’s Research Support Committee. Our family crisis, and my new role in the Foundation, occurred at a critical juncture in autism research. There has been growing scientific interest in SHANK3, a gene on chromosome 22 along with several other autism-related genes, which portend a new era of understanding and medical treatment.
While only about 1% of people with autism spectrum disorders (ASD) have SHANK3 mutations, Shank3 research has broad implications for many people with ASD. It plays an important and central role in synaptic structure, learning, and memory in autism. It interacts with many other proteins critical to neurological functioning, and some of these proteins are already implicated in other genetic forms of autism. A number of researchers have developed mouse knockout models that turn off different parts of the Shank3 protein. These models have led to behavioral, chemical and physiological assays to study the underlying molecular problems in ASD and to rapidly test candidate drugs for future clinical studies. Unlocking the mystery of Shank3 will open the door to understanding its partner proteins, providing a research path towards effective drug treatments for many ASDs.
While Shank3 research is very promising, laboratory science by itself will not lead to effective treatments. In January 2010, the PMSF’s Research Support Committee met to develop its first strategic plan for science. As a result, we prioritized several initiatives aimed at promoting all of the steps needed to ensure that research will lead to clinical gains. One of the most exciting initiatives is the Phelan-McDermid Syndrome International Registry. The Registry will collect and catalog information about the developmental, behavioral, and health profiles of individuals with PMS. The Registry will better characterize PMS, inform clinical care guidelines, and facilitate the discovery and development of therapeutics for PMS.
Our Foundation is also organizing the First International Phelan-McDermid Syndrome Symposium, which will be held on March 3 and 4, 2011. Our co-investigator is Joseph Buxbaum, Ph.D., Mt. Sinai School of Medicine. Our goal is to bring together our stakeholders to develop a plan to maximize scientific resources through coordinated efforts and to find the fastest pathways from bench to bedside. The discussions from the symposium will inform PMSF’s funding decisions as we begin to award grants and fellowships.
Charles’ seizures continue to be poorly controlled. He has social, behavioral, and communication challenges that affect every aspect of his life. After all these years, you might think I would have come to terms with all of this, but every day I feel grief. Sometimes I wonder how much more fear and heartache I can take, but Charles inevitably straightens me out! Charles has retained a joy that seems incompatible with the suffering he has endured. Every day his smile and great big dimples tell me he wants to live life and live it joyfully. How could I not pledge myself to accelerating translational PMS research? Now that I am involved, I truly appreciate the role that patient advocates can have in both supporting research and helping to steer its course.
We are now at the beginning of a very exciting time for research related to disorders like PMS and other genetic causes of autism. Advances in science, including the mapping of the human genome, new research tools, and new high-throughput drug discovery paradigms, are reshaping expectations about understanding and treating genetic conditions. Our group’s goal is not just finding medications to treat some of the manifestations of PMS, but having therapeutics that will target the underlying molecular causes. Just a few years ago, I had little reason to expect significant help from medical science, but promising new scientific work on Shank3 is inspiring hope that perhaps we will one day have a cure for PMS and related ASDs.
To learn more about the Phelan-McDermid Syndrome Foundation, please visit: http://www.pmsf.org