Highlights from the
Roundtable on the State and Future of Autism Research
Held Wednesday, March 2, 6-9pm at Stanford University
Cosponsored by Autism Society San Francisco Bay Area and the Stanford Autism Center Parent Advisory Board
Roundtable on the State and Future of Autism Research
Held Wednesday, March 2, 6-9pm at Stanford University
Cosponsored by Autism Society San Francisco Bay Area and the Stanford Autism Center Parent Advisory Board
We had a full house at our debut autism research roundtable. Because many people wished to attend but couldn't make it, here are some notes from the talks and Q&A. Notes were scribbled hastily, and all errors are mine (JE, moderator).
Featuring (l to r):
• Alycia Halladay, PhD, Autism Science Foundation (AHR)
• Joachim Hallmayer, MD, Stanford University (JH)
• Dennis Wall, PhD, Stanford University (DW)
• Antonio Hardan, MD, director, Stanford Autism Center (AH)
Moderated by Jill Escher, Escher Fund for Autism, SFASA (JE)
Selected speaker points, in roughly chronological order:
• There is much talk about immune, GI, and other issues involved in autism, but the brain is the most important organ in the disorder. We still don't know why more boys are diagnosed than girls. Autism is not a unitary disorder, we lump different things together. The heterogeneity is a challenge for research. In terms of causes, multiple factors seem to be at work. In a subset of autism, genetics is clearly driving the phenotype. There are over 200 risk genes identified, but they are not necessarily causative. They increase risk. AHR
• Epigenetics--how environmental factors affect gene function, not gene sequence—is an important and understudied area of autism research. We are finding genes converge on certain pathways, particularly with respect to how neurons grow and function. AHR
• In terms of therapies, including medical and behavioral, there's usually overlap and it's difficult to parse out which interventions are effective for which patients. Parent-mediated interventions are showing promise but it's unrealistic to expect parents to become therapists, to do the extensive work involved. AHR
• For adults, employment is understudied but important. The up-front costs may be high, but down the line there are less supervisory hours and some of the adults can go on to become taxpayers. Though we don't know why it's harder for women with ASD to remain employed. AHR
• Families are encouraged to register for It Takes Brains, an effort to collect postmortem brains of people affected by ASD. This effort is fundamental for autism research. AHR
• Compared to 20 years ago, there is vastly more funding and research directed at autism. Scientists from a variety of fields are becoming interested in autism, more people want to try to help figure it out. Autism is one of the most complex brain disorders, all areas of the brain are involved. The complexity and heterogeneity makes research challenging. AH
• A shortcoming of clinical trials is the lack of good measurements for certain outcomes, for example, social interaction. Sometimes behavioral measures are like clouds in the sky, difficult to capture and changeable throughout the day. This may skew our view regarding what's effective. We also might miss what might be effective for a subset of subjects. AH
• There is vastly more biological research in autism than when I came here to Stanford in 1989. The increase in autism research came about because of pressure from parents on the politicians and the research community. Genes that we've identified to date account for 10-20% of autism cases. At Stanford, clinically we identify genetic causes in just 7-8% of cases. JH
• One exciting area for research is induced pluripotent stem cells (IPSCs). In this method, you take cells, such as skin cells, from a subject with a disorder, and reprogram them to become neurons, which grow as clusters in a dish. You can look at the effects of specific mutations on neuron function, and you can make direct tests that you couldn't do before. But this line of research is still young. JH
• A shortcoming of IPSCs is that the epigenetic marks are erased, so it's not useful to examine epigenetic mechanisms that may be at play in autism. JH
• Progress has been slow, it's important to not overhype and we must be careful in how we interpret data. We need to think much bigger about autism research. We need to be doing research on a larger scale to make progress. With regard to heterogeneity, yes ASDs are heterogenous but treatments might not be. The treatment study area is a mess. JH
• It's not my field and people will kill me for saying this but there's little data showing the efficacy of early intervention. There are also often conflicts in terms of treatment promoters being the ones who carry out the studies. Sometimes we need more independence in autism research. JH
• Autism research is happening at a pace much slower than it should. We are piloting crowd-based data gathering, using mobile devices to relay data back to researchers. We need to be able to "fail fast" and less expensively when we try new things. It's critical to enlist "citizen scientists" to quicken the pace of data gathering. Crowd-based projects are much faster and cheper than traditional models. Shortcoming is it relies on self-report but you hope people don't misuse the system. We also need to circumscribe boundaries around the heterogeneity of autism. We need better measures to judge the quality of therapeutics. DW
* The Google Glass project is aimed to help coach kids with ASD on recognizing facial expressions and to improve eye contact. It's not a panacea, just a pilot attempt to use digital technology to bring therapies to people's homes without the expense of aides and therapists. We have a shortage of therapists, not enough boots on the ground, we need to test out more technologies to fill the voids. DW
• We are interested in molecular markers for autism, genomics, microbiomes, and tying to phenotypes. Autism phenotyping in genomics research is a lot of "garbage in, garbage out," very vague data. There are bottlenecks in terms of getting a diagnosis, an also to get services. We developed a video-based system (Cognoa) to detect autism in minutes instead of hours in a clinic. DW
• Our new genomics project will combine whole genomes with phenotype information, an open and freely accessible resource. Looking at whole families, including unaffected sibs. What's inherited? What's de novo (errors seen in affected kids but not their parents)? DW
• If you have a child with autism, the risk of having a second child is 1 in 5, or 20%. With a second child you might be able to take better advantage of early intervention. Universal screening for autism was rejected recently, putting some groups at a disadvantage. AHR
• Gene expression v gene sequence. Timing of onset may relate to gene expression, regression may be result of synaptic over-pruning. Difficult to identify these gene expression factors, they are time and tissue-specific. AHR
• There is evidence of immune dysfunction in some forms of autism, but is it associative or causative? Many genes implicated in immune function are also part of CNS development. Also, UC Davis is looking at maternal autoantibodies as related to some autism. But in autism it's not like classic autoimmune disorders. PANS is autoimmune and its symptom profile is like autism, but we don't see get positives back from the PANS clinic with the autism cases we refer. AH
• Genetics has become much more sophisticated. We can identify autism-related genes today that were unknown clinically only a few years ago. With respect to research on adults, there is growing interest. In the past the money was to fund children's research. It's a priority area at the NIH now. Clinically, recruitment is difficult after a certain age. The parents' priorities change from trying interventions to acceptance, and finding adult care. Also many DD adults live in group homes and cannot travel to clinics. AH
• The increase in autism cannot be explained by diagnostic shift alone. We would need a full-day seminar to talk about the growth of autism. But autism is growing and we need not only more research but more clinical services. We must re-look at the sheer volume of autism cases and readjust our NIH and funding priorities. AH
• Only a few causes of autism are known, with risk factors including adverse perinatal events such as prematurity, and advanced paternal age. But generally few causes are known. JH
• To track autism incidence we should use more technology, get ahead of the CDC self-report numbers that are always two years outdated when they are announced. We can follow examples of healthmap.org, flunearyou, and gapmap.stanford.edu. DW
• For early intervention, we need to identify what subgroups benefit, which don't, from what types of interventions. AH
• We should not presume all intervention must be early intervention. At later ages individuals with ASD might be more ripe for therapeutics. Earlier is not necessarily better. JH
Areas of parent interest included: risk of autism in younger siblings; not wasting time and money on ineffective interventions; sounding the alarm on the rising rate of autism; the need for research on adults with autism; gene expression in autism; carving out the heterogeneity in the autism spectrum; and more.
To receive notices about future Autism Research Roundtables, please join our email list.
Featuring (l to r):
• Alycia Halladay, PhD, Autism Science Foundation (AHR)
• Joachim Hallmayer, MD, Stanford University (JH)
• Dennis Wall, PhD, Stanford University (DW)
• Antonio Hardan, MD, director, Stanford Autism Center (AH)
Moderated by Jill Escher, Escher Fund for Autism, SFASA (JE)
Selected speaker points, in roughly chronological order:
• There is much talk about immune, GI, and other issues involved in autism, but the brain is the most important organ in the disorder. We still don't know why more boys are diagnosed than girls. Autism is not a unitary disorder, we lump different things together. The heterogeneity is a challenge for research. In terms of causes, multiple factors seem to be at work. In a subset of autism, genetics is clearly driving the phenotype. There are over 200 risk genes identified, but they are not necessarily causative. They increase risk. AHR
• Epigenetics--how environmental factors affect gene function, not gene sequence—is an important and understudied area of autism research. We are finding genes converge on certain pathways, particularly with respect to how neurons grow and function. AHR
• In terms of therapies, including medical and behavioral, there's usually overlap and it's difficult to parse out which interventions are effective for which patients. Parent-mediated interventions are showing promise but it's unrealistic to expect parents to become therapists, to do the extensive work involved. AHR
• For adults, employment is understudied but important. The up-front costs may be high, but down the line there are less supervisory hours and some of the adults can go on to become taxpayers. Though we don't know why it's harder for women with ASD to remain employed. AHR
• Families are encouraged to register for It Takes Brains, an effort to collect postmortem brains of people affected by ASD. This effort is fundamental for autism research. AHR
• Compared to 20 years ago, there is vastly more funding and research directed at autism. Scientists from a variety of fields are becoming interested in autism, more people want to try to help figure it out. Autism is one of the most complex brain disorders, all areas of the brain are involved. The complexity and heterogeneity makes research challenging. AH
• A shortcoming of clinical trials is the lack of good measurements for certain outcomes, for example, social interaction. Sometimes behavioral measures are like clouds in the sky, difficult to capture and changeable throughout the day. This may skew our view regarding what's effective. We also might miss what might be effective for a subset of subjects. AH
• There is vastly more biological research in autism than when I came here to Stanford in 1989. The increase in autism research came about because of pressure from parents on the politicians and the research community. Genes that we've identified to date account for 10-20% of autism cases. At Stanford, clinically we identify genetic causes in just 7-8% of cases. JH
• One exciting area for research is induced pluripotent stem cells (IPSCs). In this method, you take cells, such as skin cells, from a subject with a disorder, and reprogram them to become neurons, which grow as clusters in a dish. You can look at the effects of specific mutations on neuron function, and you can make direct tests that you couldn't do before. But this line of research is still young. JH
• A shortcoming of IPSCs is that the epigenetic marks are erased, so it's not useful to examine epigenetic mechanisms that may be at play in autism. JH
• Progress has been slow, it's important to not overhype and we must be careful in how we interpret data. We need to think much bigger about autism research. We need to be doing research on a larger scale to make progress. With regard to heterogeneity, yes ASDs are heterogenous but treatments might not be. The treatment study area is a mess. JH
• It's not my field and people will kill me for saying this but there's little data showing the efficacy of early intervention. There are also often conflicts in terms of treatment promoters being the ones who carry out the studies. Sometimes we need more independence in autism research. JH
• Autism research is happening at a pace much slower than it should. We are piloting crowd-based data gathering, using mobile devices to relay data back to researchers. We need to be able to "fail fast" and less expensively when we try new things. It's critical to enlist "citizen scientists" to quicken the pace of data gathering. Crowd-based projects are much faster and cheper than traditional models. Shortcoming is it relies on self-report but you hope people don't misuse the system. We also need to circumscribe boundaries around the heterogeneity of autism. We need better measures to judge the quality of therapeutics. DW
* The Google Glass project is aimed to help coach kids with ASD on recognizing facial expressions and to improve eye contact. It's not a panacea, just a pilot attempt to use digital technology to bring therapies to people's homes without the expense of aides and therapists. We have a shortage of therapists, not enough boots on the ground, we need to test out more technologies to fill the voids. DW
• We are interested in molecular markers for autism, genomics, microbiomes, and tying to phenotypes. Autism phenotyping in genomics research is a lot of "garbage in, garbage out," very vague data. There are bottlenecks in terms of getting a diagnosis, an also to get services. We developed a video-based system (Cognoa) to detect autism in minutes instead of hours in a clinic. DW
• Our new genomics project will combine whole genomes with phenotype information, an open and freely accessible resource. Looking at whole families, including unaffected sibs. What's inherited? What's de novo (errors seen in affected kids but not their parents)? DW
• If you have a child with autism, the risk of having a second child is 1 in 5, or 20%. With a second child you might be able to take better advantage of early intervention. Universal screening for autism was rejected recently, putting some groups at a disadvantage. AHR
• Gene expression v gene sequence. Timing of onset may relate to gene expression, regression may be result of synaptic over-pruning. Difficult to identify these gene expression factors, they are time and tissue-specific. AHR
• There is evidence of immune dysfunction in some forms of autism, but is it associative or causative? Many genes implicated in immune function are also part of CNS development. Also, UC Davis is looking at maternal autoantibodies as related to some autism. But in autism it's not like classic autoimmune disorders. PANS is autoimmune and its symptom profile is like autism, but we don't see get positives back from the PANS clinic with the autism cases we refer. AH
• Genetics has become much more sophisticated. We can identify autism-related genes today that were unknown clinically only a few years ago. With respect to research on adults, there is growing interest. In the past the money was to fund children's research. It's a priority area at the NIH now. Clinically, recruitment is difficult after a certain age. The parents' priorities change from trying interventions to acceptance, and finding adult care. Also many DD adults live in group homes and cannot travel to clinics. AH
• The increase in autism cannot be explained by diagnostic shift alone. We would need a full-day seminar to talk about the growth of autism. But autism is growing and we need not only more research but more clinical services. We must re-look at the sheer volume of autism cases and readjust our NIH and funding priorities. AH
• Only a few causes of autism are known, with risk factors including adverse perinatal events such as prematurity, and advanced paternal age. But generally few causes are known. JH
• To track autism incidence we should use more technology, get ahead of the CDC self-report numbers that are always two years outdated when they are announced. We can follow examples of healthmap.org, flunearyou, and gapmap.stanford.edu. DW
• For early intervention, we need to identify what subgroups benefit, which don't, from what types of interventions. AH
• We should not presume all intervention must be early intervention. At later ages individuals with ASD might be more ripe for therapeutics. Earlier is not necessarily better. JH
Areas of parent interest included: risk of autism in younger siblings; not wasting time and money on ineffective interventions; sounding the alarm on the rising rate of autism; the need for research on adults with autism; gene expression in autism; carving out the heterogeneity in the autism spectrum; and more.
To receive notices about future Autism Research Roundtables, please join our email list.
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