Archive
Infectious Behavior: The Brain-Immune Connection
The interconnectedness of the brain and immune system has become a fascinating new field of research, not only in autism but also schizophrenia and even depression. It can be complex stuff. But neurobiologist Paul Patterson, PhD, has produced a remarkably accessible and enjoyable book that intertwines history, case studies and laboratory science. He calls his slim but insightful volume Infectious Behavior: Brain-Immune Connections in Autism, Schizophrenia and Depression.
Patterson is a professor of biological sciences at the California Institute of Technology and a research professor of neurological surgery at the University of Southern California’s Keck School of Medicine. Readers of this blog may find his name and research interests familiar. Last month, we published a guest post from one of our Weatherstone Fellows who is launching her autism research career in his lab. There, Patterson and his junior colleagues are using mouse models to study how some types of maternal infection during pregnancy can increase the risk that a future child will develop autism. The research holds the potential for both deepening understanding of autism and leading to ways that pregnancy-related risks might be reduced.
Infectious Behavior explores new discoveries about the powerful biochemical communication that takes place between the brain and the immune system (which protects our bodies from infections and cancer). Patterson lets us listen in on some of this brain-immune “crosstalk,” and he explains how it can provide clues to the nature and causes of common but mysterious disorders of brain development and function. Some of this research, he argues, may shed light on today’s autism epidemic.
“Paul Patterson is attempting to describe a new field of study of which he himself is the leading pioneer,” writes Robert Freedman, MD, chair of psychiatry at the University of Colorado. “[His] efforts are unique in that they bridge the basic science and clinical world in a way that no other researcher in this field has done.”
It’s an engaging and thought-provoking read for nonscientists and scientists alike.
…More autism research news and perspective on the Science page.
I am a 26 years old with autism and many attention-seeking behaviors. What causes them? I am verbal.
Today’s “Got Questions?” answer comes from Autism Speaks Chief Science Officer Geri Dawson, PhD
Thanks so much for your question. There are many reasons why a person with autism would engage in many attention seeking behaviors. Perhaps you would like to socially interact and make friends with others, but aren’t quite sure the best way to do this. If you are being ignored by others, this might lead you to repeat your attempts to interact again and again.
If you are engaging in a behavior that is ritualized (exactly the same each time) and repetitive, it might reflect a general tendency to engage in repetitive behaviors, which is a symptom of autism. With appropriate guidance, you can learn more appropriate ways of seeking attention and this will help you develop more satisfying relationships with others. Seeking the help of a psychologist or behavior analyst may be particularly beneficial.
For more information and resources, you can follow these links to our pages on Applied Behavioral Analysis, Adults with Autism and Adult Services.
Got more questions? Send them to GotQuestions@autismspeaks.org, and join Dr. Dawson for her next “Office Hours” webchat with co-host, Joe Horrigan, MD, Autism Speaks assistant vice president and head of medical research (first Thursday of every month at 3 pm Eastern).
Thank You for Supporting our Pioneering Research
Guest post by epidemiologist Daniele Fallin, PhD, of Johns Hopkins Bloomberg School of Public Health
My work focuses on autism and understanding how genes and environments interplay to cause this developmental disorder. Much of this work is funded by federal grants, but there can be gaps in what these grants can support, especially in new fields of research. Support from Autism Speaks has been amazing in helping fill these gaps.
In particular, Autism Speaks provided important support for two of my current projects. The funding is allowing us to study families with autism and, so, gain insights into interactions between autism risk genes and environment exposures.
The Early Autism Risk Longitudinal Investigation (EARLI) is a national study of families that have at least one child on the autism spectrum and anticipate having more children. By following these high-risk families we seek to identify causes and risk factors—be they genetic, environmental or a combination of both. Information is regularly collected from mothers enrolled in the study, and their newborns receive free developmental assessments until 3 years of age.
The second study is a genome-wide investigation of DNA methylation, or epigenetics. It will allow us to investigate how various environmental exposures can affect gene expression in ways that increase—or potentially decrease—the risk of autism. This study will place special focus on environmental exposures during crucial periods of prenatal brain development.
Autism Speaks realizes the importance of these new areas of research and has put forth great effort to ensure we can explore and, hopefully, uncover risk factors for autism that, over the long term, may lead to prevention and improved treatments.
We continue to recruit study participants. Specifically we are enrolling mothers who have one or more children with autism and who may become pregnant or who are currently less than 28 weeks pregnant. They must live near an EARLI research site (California, Maryland or Pennsylvania). For more details, please visit www.EARLIstudy.org or our Facebook page.
On behalf of the EARLI research team, I want to extend a special thanks to Autism Speaks supporters for helping make this pioneering research possible.
Explore more of the studies our supporters are funding with our Grant Search Engine. And read more autism research news and perspective on the science page.
All Children Deserve Access to Communication
Guest post by Connie Kasari, Ph.D., Center for Autism Research & Treatment, UCLA Semel Institute
ABC 20/20 recently aired a tragic story that brings up anew the controversy surrounding the intervention called Facilitated Communication (FC). Faced with a lack of success with prior efforts, the family reached out to include FC (an intervention involving a “facilitator” who physically supports the arm of the individual as they use a keyboard to type). As the story is told, the facilitator, trained for only one hour, assisted the child in making salacious sexual abuse allegations against her father. As the investigation evolves, the case against the father falls apart. FC and the facilitator become the focus of scrutiny, while the family is torn apart.
This story will undoubtedly strike many chords with families and researchers alike. As a tragic case in point, the story highlights the desperation families feel in trying to find an intervention that can help their older, nonverbal person. Multiple research studies have rejected the benefits of FC, mainly because the purported effects of the therapy are often the thoughts of the facilitator and not the child, as was discovered in the 20/20 story (Jacobson et al, 1995). Professional organizations have not supported the use of FC with consistent position statements from the American Academy of Child and Adolescent Psychiatry (1993), the American Academy of Pediatrics (1998), American Association on Intellectual and Developmental Disorders (1994), the American Psychological Association (1994), the American Speech Language and Hearing Association (1994) and the Association for Behavior Analysis (1995). Yet parents still reach for disproven therapies, and even compel their schools to provide the therapy despite the research evidence.
Part of the issue here, is that there are few evidence -based communication interventions that have shown benefit to older, school aged children. This situation gives rise to the adoption of less effective interventions and should continue to call on researchers to pay greater attention to this group of individuals with autism. Indeed, the Interagency Coordinating Council for Autism, the National Institutes of Health and Autism Speaks have all placed a high priority on the development of innovative interventions for nonverbal individuals with autism.
While early intervention has decreased the numbers of nonverbal individuals, estimates are that between 30% and 40% of children with autism spectrum disorders remain minimally verbal, even after receiving years of interventions (NIH workgroup, 2010). Having access to communication is critical for all children. Augmentative systems can provide children with a voice, and some children have developed verbal abilities via typing or other communicative systems. Thus, the culprit in the intervention described in the 20/20 story was not the use of a keyboard but the methods used to help the child communicate. Teaching a child to use a keyboard often involves a period of physical prompting to teach the act of typing, but eventually the child should type independently, using little or no physical prompts. The addition of augmentative and alternative communication systems can have a profound effect on children’s ability to communicate, and indeed there are many cases of children who are able to type their responses or to use other augmentative systems. Witness the explosion of the iPad and speech generating applications for children with autism. These augmentative systems can result in improved communication and even increases in spoken language, although the evidence to date is anecdotal or limited to single case designs (Schlosser & Wendt, 2008).
High quality research studies are beginning to address this population of children who are school aged, and minimally verbal. Autism Speaks has funded a High Risk, High Impact intervention study on this population. The Characterizing Cognition in Nonverbal Individuals with Autism (CCNIA) intervention study is conducted at three sites: UCLA, Vanderbilt and Kennedy Krieger Institute and will finish this year.
CCNIA Intervention Study (Kasari, Kaiser, & Landa, 2009): Participants include children who are 5 to 8 years of age, produce fewer than 20 functional words, and who have already had at least two years of intensive intervention but are still not “talking”. The study utilizes an innovative design called a SMART (Sequential Multiple Assignment Randomized Trial) design (Murphy, 2005). This design recognizes the importance of consolidating early successes in treatment such that children are re-randomized to increased intensity of intervention or to the alternate intervention if they are not responding to the initial intervention to which they were randomized.
The interventions involve the merging of two evidence- based communication therapies JASPER (Joint Attention, Symbolic Play, Engagement & Regulation, Kasari et al, 2006, 2008, 2010); and EMT (Enhanced Milieu Training, Kaiser et al, 2000) with children randomized to JASPER/EMT only or to JASPER/EMT with the addition of a speech generating device. Children receive intervention twice per week for three months. Progress towards the initiation of socially meaningful communication is then evaluated. If children have met the defined criteria for improvement in communication, they stay the course for another three months. If they have not progressed they are re-randomized to receive increased intensity of the same therapy or to receive the speech-generating device if they received only the spoken language intervention initially. Children are followed up for three months after the six months of intervention.
While we won’t know the benefit of these interventions until the study is completed later this year, we believe that minimally verbal school aged children require an intervention approach that simultaneously (a) consolidates their early successes in intervention, and (b) adapts interventions to maximize their effects if there are early indications of non-response to the interventions. Sequential adaptations of intervention protocols may be needed to place all minimally verbal individuals on a positive, long-term course toward developing expressive language.
Works Cited:
Interagency Autism Coordinating Committee (2011). 2011 IACC Strategic Plan for Autism Spectrum Disorder Research. http://iacc.hhs.gov/strategic-plan/2011/index.shtml.
Jacobson JW, Mulick JA, Schwartz AA. (1995). A history of facilitated communication: Science, pseudoscience, and antiscience: Science Working Group on Facilitated Communication. American Psychologist, 50, 750-765.
Kaiser, A. P., Hancock, T. B., & Nietfeld, J. P. (2000). The effects of parent-implemented enhanced milieu teaching on the social communication of children who have autism. Journal of Early Education and Development [Special Issue], 11(4), 423-446.
Kasari, C., Freeman, S., & Paparell, T. (2006). Joint attention and symbolic play in young children with autism: A randomized controlled intervention study. Journal of Child Psychology and Psychiatry, 47, 611-620.
Kasari, C., Gulsrud, A.C., Wong, C., Kwon, S., & Locke, J. (2010). A randomized controlled caregiver mediated joint engagement intervention for toddlers with autism. Journal of Autism and Developmental Disorders, 40, 1045-1056.
Kasari, C, Kaiser, A., & Landa, R. (2009). Developmental and Augmented Intervention for Facilitating Expressive Language. Sponsored by Autism Speaks, Grant 5666.
Kasari, C., Paparella, T., Freeman, S., & Jahromi, L.B. (2008). Language outcome in autism: Randomized comparison of joint attention and play interventions. Journal of Consulting and Clinical Psychology, 76, 125-137.
Murphy, S.A. (2005). An experimental design for the development of adaptive treatment strategies. Statistics in Medicine, 24, 1455-1481.
Schlosser, R., Wendt, O (2008). Effects of augmentative and alternative communication intervention on speech production in children with autism: A systematic review. American Journal of Speech-Language Pathology, 17 , 212–230.
The Year in Review from Autism Speaks’ Chief Science Officer
Dear friends,
When I was a college student starting to explore autism research, one of the first studies I read provided strong evidence that autism was mostly a genetic condition. That study, by Michael Rutter and Susan Folstein, looked at 21 pairs of twins, at least one of each pair being affected by autism. It compared identical twins, who share all of their genetic makeup, with fraternal twins, who share around half their genes. It found that when one identical twin had autism, so did the other 83 percent of the time. By contrast, this was true of only 10 percent of the fraternal twins. For the next three decades, it was taken as fact that the causes of autism were almost completely genetic.
That changed this past year with the largest ever autism twin study, made possible by your support for Autism Speaks and its Autism Genetic Resource Exchange (AGRE). Read more …
How common are anxiety disorders in people with autism, and are there effective treatments?
This week’s “Got Questions” answer comes from Rob Ring, PhD, Autism Speaks vice president of translational research.
Without question, anxiety is a real and serious problem for many people on the autism spectrum. We hear this from parents, teachers and doctors, as well as from adolescents and adults with autism spectrum disorder (ASD). This disabling anxiety can take the form of one or more disorders, including panic disorder and phobias.
A recent review of scientific studies on autism and anxiety revealed that we have no clear gauge of how commonly anxiety disorders overlap with autism. A few small, relatively short-term studies have produced starkly different results: from 11 percent to 84 percent. (For comparison, the prevalence of anxiety disorders among the general population is about 18 percent.) A reliable estimate will require a study that tracks many more individuals with autism over longer periods of time and that considers the distinctive way that anxiety oftentimes expresses itself in those affected by ASD.
Fortunately, Autism Speaks is funding the Autism Treatment Network, which collects systematic data on a wide range of medical conditions, including anxiety disorders, in children with ASD. This data will help us better understand the proportion of people with ASD who are suffering from anxiety symptoms.
Meanwhile preliminary studies have provided insights. They suggest, for example, that adolescents with autism may be particularly prone to anxiety disorders, while younger children on the spectrum may not differ at all from the average population. Some studies likewise suggest that high-functioning individuals on the spectrum experience higher rates of anxiety disorders than do lower-functioning individuals. Still we must emphasize that these results are preliminary. We don’t know nearly as much as we should about how anxiety disorders affect those with autism.
A recent review of studies found that behavioral interventions can help many children and adolescents with autism who also struggle with anxiety. Along these lines, some studies suggest that cognitive behavioral therapy can be particularly helpful for high-functioning adolescents and adults with autism and anxiety. We will explore behavioral interventions further in a future “Got Questions?” blog. My own expertise is in the medical treatment of anxiety in persons with ASD.
Currently, we have no medications approved by the Food and Drug Administration (FDA) expressly for the treatment of anxiety in children, adolescents or adults with autism. Some classes of drugs commonly prescribed for treating anxiety disorders in the general population likewise help some of those on the autism spectrum. These include the selective serotonin reuptake inhibitors (SSRIs) such as Prozac. For those with autism, anxiety drugs are best used in combination with behavioral interventions. Among high-functioning individuals, they may be particularly effective when combined with cognitive behavioral therapy.
However, some doctors report that anti-anxiety medications seem to be less effective overall in people with autism spectrum disorder than they are in the general population. This observation needs to be verified with controlled research. It suggests the possibility that the biological root of anxiety in those with autism may differ from the “norm” and, as a result, may respond best to different treatments.
At Autism Speaks, we are actively supporting research into anxiety disorders and other medical conditions frequently associated with autism. This includes both basic research on the underlying biology of autism and the safe development of drugs that can relieve disabling symptoms and improve quality of life.
If you are considering anti-anxiety medication for a child with autism, our recently published Medication Decision Aid can help you work with your child’s physician to sort through the pros and cons in the context of your values and goals for your child. You can learn more about the medication tool kit and download a free copy, here.
Got more questions? Send them to GotQuestions@autismspeaks.org. And bring them to our next webchat with Autism Speaks Chief Science Officer Geri Dawson, Ph.D., and Autism Speaks assistant vice president and head of medical research Joe Horrigan, M.D. More information on their monthly webchats here.
Transcript of Today’s Office Hours Webchat
| Office Hours Webchat with Geri Dawson and Joe Horrigan Jan 5. Thanks to the more than 200 readers who joined us. As time allowed answering just a portion of more than 100 questions, we hope you’ll join us again next month—Feb. 2 (first Thursdays) at 3 pm Eastern. |
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Commentary on the LA Times Series on Autism
Posted by Autism Speaks scientific advisory board member Irva Hertz-Picciotto, PhD, MPH. As an epidemiologist at the University of California-Davis MIND Institute, Hertz-Picciotto studies exposures to environmental chemicals, their interactions with nutrition and pregnancy and their effects on prenatal and early child development.
Alan Zarembo’s series on autism in the LA Times covers a great deal of territory and has brought to light a wide range of personal stories that exemplify the complexity of issues surrounding autism diagnosis, treatment choices and effectiveness, impact on families and population incidence. Zarembo should be commended for the substantial work he has done researching inequities in the delivery of services. Of notable concern, he has put a spotlight on what appear to be serious racial and ethnic disparities in the California Department of Developmental Services (DDS) system and the provision of therapies. If his figures are correct, this result should stimulate an analysis of how to right this situation and ensure that appropriate opportunities are made available to all families with affected children.
Zarembo has also highlighted adults living with an autism spectrum disorder (ASD) but diagnosed late in life. We have too long overlooked the struggles faced by adults with autism as they try to find ways to be productive, live independently and connect with others.
My remaining comments pertain to Zarembo’s conclusions about the rise in autism diagnoses and the role of environmental factors. First, he is right that there is substantial variability in rates of diagnoses in different regions, and that we should not confuse diagnoses with the actual incidence of disease. Not all persons who meet criteria have been correctly diagnosed, and the degree to which this is true has likely changed over time.
Nevertheless, impressions are not the same as a scientific analysis. Zarembo has not demonstrated that the rise is purely social and cultural. My colleague Lora Delwiche and I published the first quantitative analysis of how much of the increase in diagnosed cases in California could be explained by artifacts (changes in diagnostic criteria, earlier age at diagnosis and inclusion of milder cases).1 We used California state data that provided statistics over many years and found that the numbers simply do not add up. In other words, the actual increase has been far larger than these artifacts could have produced. Combining our results with those of another research team, it appears that about half of the increase in diagnoses in California is due to changes in diagnostic criteria or practices.2 These results left about a three-fold increase unexplained as of 2007. And autism diagnoses in California have continued to rise both in areas with low rates and in areas with high rates. Zarembo is interested in explaining the geographic variation, but the explanations for variation spatially are not necessarily the explanations for variation over time.
These statements were particularly misleading:
“No study points to an environmental reason for the worldwide explosion in cases over the last two decades.
Given the slow pace of genetic change in large populations, genes can’t account for the surge either.
That suggests the explanation for the boom lies mainly in social and cultural forces, notably a broader concept of autism and greater vigilance in looking for it.”
The logic that leads from the first two sentences to the third involves huge assumptions.
How many studies have been done of environmental causes? Very few! And of these, most were extremely poor studies involving very small samples or lacking individual-level data. Is it surprising we’ve uncovered few leads? The funding for environmental factors has been paltry – somewhere around $40 to $60 million over the last 10 years, while more than $1 billion has been spent on studying autism genetics. To imply that environmental factors can be dismissed and that only social/cultural factors should be pursued is nonsensical.
It should be noted, however, that if anyone is looking for “one” environmental factor to explain the increase, they will certainly be disappointed. It doesn’t exist. Autism is far too complex. Moreover, to the extent the increase is due to diagnostic differences over time, we need to find explanations both for the increasing numbers of diagnoses and for the autism that has been around “all along.” In fact, data are emerging about quite a number of environmental factors. In 2011, major papers were published supporting contributions from maternal nutrition around the time of conception (here and here), traffic-related air pollution, and season of conception.3-6 Earlier papers indicated associations with pesticides (here and here) and air pollution.7-9
One concern raised about the increase in diagnoses is a type of ‘inflation’ from inclusion of a growing number of high-functioning persons whose diagnosis is more likely to be Asperger syndrome than classic autism. This may apply to some studies of changes over time, but in our analysis of CHARGE study data, most of the cases were low functioning.10 This would likely be true for the majority of persons with ASD served by the California Department of Developmental Services (DDS), because in order to qualify for state services, they must have “significant functional limitations” in three areas of major life activities. This requirement would exclude most of those who are higher functioning.
With regard to genetics, Zarembo’s article leaves out the most current information: the largest and most statistically robust study of twin pairs found that 38 percent of concordance is due to shared genetics with 58 percent due to shared environmental factors (most likely prenatal and perinatal).11 This result completely overturns the widespread assumption, based on a number of previous small studies, that the causes of autism are overwhelmingly heritable, or genetic. Unfortunately, most analyses of twins make the incorrect assumption that genes and environment do not interact to influence risk for disordered brain development. This interaction is real, and one study has already shown a whole class of genes that primarily affect development in children whose mothers had not taken prenatal vitamin supplements during the months preceding and immediately following conception. 3
In summary, Zarembo’s investigative journalism provides unusual depth into difficult aspects of autism occurrence and the social policies that bear on the lives of affected families. He has raised several critical challenges facing the autism community. What was lacking from his series is a more balanced view of the role environment likely plays and the need to advance the agenda of discovering modifiable causative factors.
Autism Speaks is one of a few organizations that have begun to turn in this direction. I look forward to a continued strong commitment by Autism Speaks and others willing to support and significantly expand the scientific research aimed at identifying and understanding environmental contributions to autism, factors driving increased prevalence and ways to intervene so as to eliminate or lower human exposure levels. This will be the fastest road to reducing the occurrence of ASD in the next generation.
References
1 Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009;20: 84-90.
2 King M, Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol. 2009; 38:1224-34.
3 Schmidt, R J, et al. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 2011;22:476-85.
4 Cheslack-Postava K, Liu K, Bearman PS. Closely spaced pregnancies are associated with increased odds of autism in California sibling births. Pediatrics 2011;127:246-53.
5 Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect 2011;119: 873-7.
6 Zerbo O, Iosif AM, Delwiche L, Walker C, Hertz-Picciotto I. Month of conception and risk of autism. Epidemiology 2011;22:469-75.
7 Roberts EM, et al. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007;115:1482-9.
8 Eskenazi B, et al. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect 2007;115:792-8.
9 Windham G, Zhang L, Gunier R, Croen L, Grether J. Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco Bay Area. Environ Health Perspect. 2006; 114(9):1438-44.
10 Hertz-Picciotto, I. et al. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006;114: 1119-25.
11 Hallmayer, J. et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011(68):1095-102.
Music as a Path to Language in Autism
Today’s guest blog post is from Gottfried Schlaug, MD, PhD, director of the Music and Neuroimaging Laboratory and associate professor of neurology at Beth Israel Deaconess Medical Center and Harvard Medical School, in Boston. He is a recent recipient of an Autism Speaks Treatment Research Grant.
As many as three in ten children with autism are nonverbal. Yet many children with autism have superior auditory skills and a particular attraction to music. Based on these observations, I and my colleagues have been using forms of music-making that encourage vocalization as a pathway to developing language.
We call our therapy Auditory-Motor Mapping Training (AMMT), and our approach is built on two findings.
First research has shown that music-making creates clear changes in the human brain. In particular we know that it engages and strengthens connections between the auditory and motor regions and improves mapping of sounds to actions. Second, here at our Music and Neuroimaging Lab, we have successfully used a form of singing (i.e., Melodic Intonation Therapy) to help stroke patients regain speech lost after a stroke (aphasia). In essence, our therapies involve having the patient sing words and phrases while using a coordinated movement of the hand not affected by the stroke. This helps their brains map sounds to actions.
In recent years, we’ve adapted our music-motor therapy for stroke victims in ways that allow us to use it with children who have autism and little or no speech. In simplified terms: Our team members sing words and phrases with social connotations (for example, “more please,” “mommy,” “all done”) to the children and with the children, while showing them pictures of the action, person or object. At the same time, we guide each child’s hand to play two drum pads tuned to different pitches.
We believe that intensive, repetitive training—pairing sound with actions–can engage and strengthen the brain pathways needed to speak. In our recently published “proof of concept” study, each participant received 40 treatment sessions, conducted 5 days per week over an 8 week period, with each session lasting 45 minutes. Further analysis revealed that the therapy’s benefits probably occur in the first 25 sessions.
We have seen very encouraging results in our pilot and proof-of-concept studies and are now excited to expand our research and therapy program with a 2011 treatment grant from Autism Speaks. In other words, this funding and this study are being made possible by you—Autism Speaks’ community of supporters. Thank you. We look forward to reporting back our results! Meanwhile, please visit our lab’s website: http://www.musicianbrain.com.
Read more science news and perspective on the science page. And explore more of the studies we’re funding with our grant search.
Can Topotecan Relieve Angelman Syndrome?
Posted by Eileen Braun, executive director of the Angelman Syndrome Foundation, and Joe Horrigan, M.D., Autism Speaks assistant vice president and head of medical research
Today brings the publication of findings on a group of compounds whose potential for treating Angelman syndrome deserves both kudos and cautious optimism. This rare condition, often classified as an autism spectrum disorder (ASD), is marked by developmental delays, lack of language, seizures and difficulties with balance and walking. Many individuals with Angelman syndrome require lifelong care.
In research initially funded by the Angelman Syndrome Foundation, neurobiologist Ben Philpot and his team at the University of North Carolina, Chapel Hill, screened over 2,300 compounds to find several that, in mice, activate production of a brain protein whose absence causes Angelman syndrome in humans. The tremendous public interest in this report stems from the fact that one of the compounds identified in the paper is available as an FDA-approved chemotherapy drug (topotecan, or Hycamtin) for small cell lung cancer that fails to respond adequately to first-line treatments. [See our related news report, “Topoisomerase Inhibitors and Angelman Syndrome.”]
While we are heartened by the UNC team’s identification of potential medicines for the treatment of Angelman syndrome, we are deeply concerned that this news could produce expectations that lead some families to prematurely seek this drug for their loved ones–that is, before it is safe to do so. As a community, we should welcome the news, but we cannot let it risk unintended harm by side stepping the proper due course of research. The next phase of research is critical to assessing safety and effectiveness.
Our concerns are several-fold: First, the findings from this study represent a very early stage of the drug discovery process. As the UNC scientists are quick to point out, they have yet to determine whether these compounds actually relieve symptoms in animal models of Angelman syndrome—let alone whether they can benefit children or adults affected by this disorder. Along the same lines, it is unclear if medicines like topotecan affect human cells in the same way that they affect the cells of mice. In addition, these agents can have serious side effects. For example, we must remember that chemotherapy drugs such as topotecan are designed to kill cells—primarily cancerous ones, of course. But they also affect healthy cells. Potential side effects of topotecan include bone marrow suppression, which is associated with a sometimes dramatic decrease in the production of blood cells. In addition, topotecan can cause fetal harm when administered to a pregnant woman.
On a practical level, determining an effective but safe dose of a medicine like topotecan can be difficult for even a cancer specialist. Also, a medicine like topotecan was not designed for use over extended periods of time, but rather as one of the last resorts for patients with a deadly form of cancer that does not respond adequately to other treatments. All of these factors need to be considered carefully by the readers of this important paper by Dr. Philpot and his colleagues.
We feel it is especially important to view this study’s promising findings in the light of other experimental medicines now entering the autism research pipeline. We look forward to these potential medical treatments being carefully studied for safety and effectiveness first in animal models and human tissue samples. Only then should the safest and best candidates be considered for advancement into clinical trials.
The critical point is that there are no short cuts to drug development when it comes to safety.
This raises a second, very important issue for our families. As promising as any experimental medicine may be, one needs to carefully consider what it means for you or your child to be part of a clinical drug trial. The potential benefits and risks associated with being a research participant can be quite different from those experienced as a person receiving medical care from a personal physician or other healthcare professional. As a result, the decision to become a research participant should be approached with careful thought and discussion.
For these reasons, we’re working together to create a “Participant’s Guide to Autism Drug Research.” Please look for its release on this science blog and on the “Participate in Research” page of Autism Speaks website in the coming weeks. You can also stay up-to-date with this research as it relates to Angelman syndrome via the Angelman Syndrome Foundation’s website at www.angelman.org.
Have more questions? Send them to GotQuestions@autismspeaks.org and bring them to “The Doctors Are In,” our monthly live webchat with clinical psychologist and Autism Speaks Chief Science Officer Geri Dawson, PhD, and her co-host, pediatric psychiatrist and Autism Speaks Head of Medical Research Joe Horrigan, MD.
