IACC Strategic Plan Update Question 2 (Biology) Planning Group Conference Call Announcement - November 8, 2013
Announcement
| Topic | Topic Description |
|---|---|
| Date: | Friday, November 8, 2013 |
| Time: | 1:30 p.m. to 3:30 p.m. Eastern |
| Agenda: | The planning group for Question 2 (Biology) will discuss updates for the IACC Strategic Plan. |
| Place: | No in-person meeting; conference call only |
| Conference Call: | Dial: (888) 790-1954 Access code: 8779895 |
| Materials: | Meeting materials |
| Contact Person: | Ms. Lina Perez Office of Autism Research Coordination National Institute of Mental Health, NIH 6001 Executive Boulevard, NSC, Room 6182A Rockville, Maryland 20852 Phone: (301) 443-6040 E-mail: IACCPublicInquiries@mail.nih.gov |
| Please Note: | The conference call will be open to the public in listen-only mode. Members of the public who participate using the conference call phone number will be able to listen to the meeting but will not be heard. If you experience any technical problems with the conference call, please e-mail HelpDeskIACC@gmail.com or call the IACC Technical Support Help Line at 415-652-8023. Accommodations Statement: The meeting will be open to the public via conference call. Individuals who participate by using this electronic service and who need special assistance such as captioning or other reasonable accommodations should submit a request to the Contact Person listed on this notice at least 1 day prior to the meeting. Schedule subject to change. |
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Agenda
No in-person meeting; conference call only. The materials for the meeting can be found here.
| Time | Event |
|---|---|
| 1:30 p.m. | Roll Call and Opening Remarks Susan Daniels, Ph.D. Acting Director, Office of Autism Research Coordination, National Institute of Mental Health Executive Secretary, IACC |
| 1:40 p.m. | Discussion of Progress Toward Meeting Strategic Plan Question 2 Objectives "How Can I Understand What Is Happening?" (Underlying Biology of ASD) |
| 2:55 p.m. | Discussion of Progress Toward Meeting Question 2 Aspiration Goal: "Discover How ASD Affects Development, Which Will Lead To Targeted And Personalized Interventions." |
3:25 p.m. | Wrap-up and Next Steps |
| 3:30 p.m. | Adjournment |
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Minutes
- Roll Call and Opening Remarks
- Discussion of Question 2 IACC Portfolio Analysis Documents and Strategic Plan Progress
The Interagency Autism Coordinating Committee (IACC) Subcommittee for Basic and Translational Research Strategic Plan Question 2 Planning Group convened a conference call on Friday, November 8, 2013, from 1:36 p.m. to 3:25 p.m.
In accordance with Public Law 92-463, the meeting was open to the public. Susan Daniels, Ph.D., Executive Secretary, IACC, presided.
Participants:
IACC Members and Staff:
Walter Koroshetz, M.D., Chair, National Institute of Neurological Disorders and Stroke (NINDS); Susan Daniels, Ph.D., Executive Secretary, IACC, Office of Autism Research Coordination (OARC), (NIMH); Lyn Redwood, R.N., M.S.N., Coalition for SafeMinds; Alison Tepper Singer, M.B.A., Autism Science Foundation (ASF)
Invited External Speakers:
Nancy Minshew, M.D., University of Pittsburgh; Carlos Pardo-Villamizar, M.D., Johns Hopkins Medical Center; Kevin Pelphrey, Ph.D., Yale University;
Roll Call and Opening Remarks
Dr. Susan Daniels welcomed the Planning Group and members of the public, and called roll. She said that this Group was charged with the update for Question 2 of the IACC Strategic Plan (How Can I Understand What is Happening?). She noted that the goal of this call of the Planning Group was to qualitatively evaluate the scientific progress made on the Question 2 objectives, and to identify any gaps with the help of external experts. In addition, the Group was to discuss progress made toward the aspirational goal of Question 2.
Discussion of Question 2 IACC Portfolio Analysis Documents and Strategic Plan Progress
Dr. Daniels reviewed materials prepared by the Office of Autism Research Coordination to provide funding and project information for Planning Group reference. All of the materials are available online. The materials included: a Compiled Objectives (cumulative funding) Table, a Project Data Table (2008-2010), and a Conclusions Table. The Compiled Objectives (cumulative funding) Table showed the alignment of funding across years (2008-2012) for each objective in Question 2. A Project Data Table (made available for the previous conference call) was provided to the Committee members, and is available online. This Table included some live links for 2008-2010 projects the 2008 through 2010. The Conclusions Table was a compilation of initial determinations about the funding progress on Question 2 objectives made by Question 2 Planning Group members during the previous conference call. This table provided a brief summary of the discussion of each objective.
Dr. Daniels guided the Group through discussions of research progress, gaps, and barriers for each of the objectives. She began each discussion by reviewing the overall conclusions from the previous call regarding funding, projects, and conclusions.
2.S.A Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010. (Fever studies to be started by 2012) The Planning Group previously had agreed that the recommended budget had been met, and many projects had been funded. However, the field was still developing, and there was a need for continued emphasis. Dr. Carlos Pardo-Villamizar said that fever may modify behavior in children with autism. However, the mechanism is not known. A number of genes had been associated with innate immunity, and this was his pick for the biggest advance in the last year.1 Dr. Pardo-Villamizar added that better characterization of the immunological background of these patient populations was also an important advancement.2
Dr. Walter Koroshetz mentioned recent animal models that have been developed based on mothers with immune challenges in the first or second trimester.3 Dr. Pardo-Villamizar said that the interaction of maternal environment and the genetic background also was critical for understanding autism. It would be necessary to better understand how the innate immune system and other elements of the immune system intervene during brain development. This area needed much more work. He added that there was also interest in the potential effect of neurotoxins with respect to the maternal environment. Ms. Lyn Redwood said that fever was of particular interest from a family perspective.
There was a brief discussion of the types of studies that could answer questions about the role of fever. Also, there was a brief discussion of Positron emission tomography (PET) imaging studies of microglia.4 Dr. Pardo-Villamizar commented that it would be important to understand the stage of microglia activation in the brain of patients with autism. Dr. Koroshetz noted that there are some cases where mitochondrial disorders and ASD co-occur. Dr. Pardo-Villamizar said that the difficulty with studying the role of mitochondria in autism is that the prevalence of mitochondrial defects in the general population is unknown. It would also be difficult to determine whether oxidative stress is involved. Dr. Nancy Minshew said that the real need was the development of research methods to understand these disorders. She suggested a workshop to bring together experts to address this need. Ms. Redwood proposed including clinicians who work with children with mitochondrial disorders.
2.S.B Launch three studies that specifically focus on the neurodevelopment of females with ASD, spanning basic to clinical research on sex differences by 2011. Previously the Planning Group agreed that the overall recommended budget had been partially met, and more than three studies specified by the Strategic Plan had been launched. In addition, there was an Autism Center of Excellence (ACE) focused on females with autism. They felt, however, that although there has been progress in line with Strategic Plan goals, further work is needed to move this field forward. Dr. Kevin Pelphrey said research from the ACE showed differences in how copy number variations (CNVs) played roles in autism in boys and girls. The major protective factor for girls appeared to be that they could withstand a greater "hit" in terms of the number and size of CNVs before symptoms appeared.5 Ms. Alison Singer observed that there was also emerging work on treatment response differences in males and females. They also touched briefly on the concept of "carrier moms" idea of females who had the genetic hits but did not express the clinical phenotype. These individuals could help with a better understanding of a potential protective factor.
2.S.C Identify ways to increase awareness among the autism spectrum community of the potential value of brain and tissue donation to further basic research by 2011. The Planning Group agreed that the overall recommended budget had been partially met. Dr. Daniels said that in 2013 the NIH launched the NIH NeuroBioBank, which included samples for research on autism, as well as other brain disorders. However, funding for this initiative was not reflected in this objective because the project was not autism-specific. She noted that the NeuroBioBank had an accompanying Web publication, Live Brain Donation: A Legacy of Hope (PDF – 946 KB), which addressed the value of brain donation. Ms. Singer said that in the nonprofit arena, the Simons Foundation and Autism Speaks were funding the Autism BrainNet brain bank initiative that aimed to collect, process, store, and distribute postmortem brain samples for autism research. In addition, there would be a coordinated outreach and awareness program targeting families and other stakeholders in the autism community. Dr. Pardo-Villamizar commented that there was a great need for brain tissue from individuals with ASD for research- with no more than 10 new cases available for study each year, currently. He also noted that another current research challenge was the need to establish a collection of normal brains for use as controls.
2.S.D Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g., Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. The Planning Group agreed that the recommended funding had been met. There were a large number of funded projects, going beyond the three recommended in the objective, and, there had been growth in this area. In particular, tuberous sclerosis was the focus of research at an NIH ACE, Dr. Daniels noted. Dr. Koroshetz said that this area is one that had progressed the most over the last 5 years. Emerging information about these monogenic, highly penetrant disorders that frequently have an autism phenotype had led to the identification of potential pathways that could be causally linked with the disorders. Generalization to non-syndromic forms of autism would require further research, but the way had been paved by the investment of funding in this area.
2.S.E Launch three studies that target the underlying biological mechanisms of co-occurring conditions with autism, including seizures/epilepsy, sleep disorders, wandering/elopement behavior, and familial autoimmune disorders, by 2012. The Planning Group agreed that the recommended budget had been met. More than 20 projects had been funded, and thus going beyond the three projects recommended, but the group felt that scientifically, additional efforts were needed, especially related to wandering, and metabolic and immune conditions related to ASD. Dr. Pelphrey said that the objective was too broad. Each component would require different approaches and methods. He suggested that it would be better to separate these topics, for example, wandering/elopement was an issue that could be addressed partly and rapidly through increased community awareness campaigns and other approaches.
The Group discussed potential factors that could play a role in co-occurring seizures - synaptic dysfunction, immune activation, CNV mutations, neurologic disorganization, and inflammation. They agreed that more research was needed. In terms of familial autoimmune disorders, Dr. Pardo-Villamizar said that the best approach would be to conduct well-designed epidemiological characterizations at large centers. In terms of sleep disturbances, Dr. Minshew noted that there were a broad range of potential contributors. There were also alterations of circadian rhythms that might be related to genetic alterations. Ms. Singer suggested seeking information from sleep expert Dr. Beth Malow of Vanderbilt University. Dr. Daniels summarized that more research was needed to understand the biology of each of these conditions.
2.S.F Launch two studies that focus on prospective characterization of children with reported regression to investigate potential risk factors by 2012. The Planning Group agreed that the recommended budget had been partially met. Further work was needed to compare regressive autism to nonregressive autism; high-risk siblings would be a useful population to study. Dr. Pardo-Villamizar said that regression/nonregression was now considered to be part of a continuum, rather than a dichotomy, as recent reports suggested more gardula and varied patterns of gain and loss of skills in individuals. It might be that regression was not a different form of autism. Dr. Minshew and Dr. Pelphrey agreed, but added that this conclusion might not be based on empirical data. Their imaging research involved high-functioning individuals with ASD, not catastrophic or late regressive cases. Dr. Pelphrey said that his unpublished imaging research on regressive cases, especially when accompanied by low IQ, revealed very different brain phenotypes than for individuals with high-functioning autism. There wasn't enough data yet to make any conclusions about whether regressive autism was a different kind of autism though. Dr. Minshew said that research was ongoing. She commented that it was important to keep both the autism science community and the public aware of these issues.
2.S.G Support five studies that associate specific genotypes with functional or structural phenotypes, including behavioral and medical phenotypes (e.g., nonverbal individuals with ASD and those with cognitive impairments) by 2015. The Planning Group agreed that the recommended budget had been met, and that funding was at the right level. Dr. Koroshetz said that imaging and genetics could be used to define particular subgroups. Dr. Pardo-Villamizar agreed and added that to be successful in identifying sub-groups; these studies would need to be carried out through multicenter consortiums with large patient pools. Dr. Minshew said that they should consider initiating these types of efforts soon.
2.L.A Complete a large-scale, multidisciplinary, collaborative project that longitudinally and comprehensively examines how the biological, clinical, and developmental profiles of individuals, with a special emphasis on females, youths, and adults with ASD, change over time as compared to typically developing people by 2020. The Planning Group agreed that the recommended budget had been partially met, and a number of projects had been funded. However, more longitudinal clinical studies were needed to identify issues faced by people with ASD as they aged. Dr. Pelphrey noted that future research should especially target important concerns of adults with autism (e.g. transition to adulthood).
Dr. Minshew said that very little was known about the transition from childhood to adolescence, and then to adulthood. Ms. Redwood said that this was a very critical area of research because some adolescents with ASD were beginning to "age out of the system" of child-related services. It was unclear how their future healthcare, housing, employment, and other needs would change with time. She also expressed concern about securing the funding necessary for expensive large longterm projects that need to be conducted.
2.L.B Launch at least three studies that evaluate the applicability of ASD phenotype and/or biological signature findings for performing diagnosis, risk assessment, or clinical intervention by 2015. The Planning Group agreed that the recommended budget had been partially met. More than three studies had been launched, but more funding and more work was needed. Dr. Minshew commented that this was an area that was still evolving.
As an example, in order to make progress in identifying brain alterations, more sophisticated imaging methods and tracers would be needed. Dr. Koroshetz said that the recent Autism Brain Imaging Data Exchange (ABIDE)6 landmark study provided a new model for the field. ABIDE was a grassroots consortium that aggregated and openly shared more than 1,000 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information. Dr. Pelphrey cautioned that standardization would be crucial for these types of studies. Dr. Minshew said that with regard to the objective, there were two components. One component was methods development and discovery. The other component was methods standardization.
ASPIRATIONAL GOAL: Discover how ASD affects development, which will lead to targeted and personalized interventions.
Dr. Minshew and Dr. Pelphrey agreed that there had been progress in terms of effective behavioral treatments.7, 8 They also mentioned good results using peers to improve social function, and how jobs for adults had resulted in documented improvement in executive function and working memory.9, 10 Dr. Pelphrey noted that treatment studies involving neurophysiology and imaging as outcome measures would be an area of increasing future research, especially for subvariables – for example, how genetic data could predict treatment response. Dr. Minshew agreed that this was a trend, and mentioned one of her studies of neural cognitive intervention for adults. It included fMRI measures relevant to the intervention areas.
Ms. Redwood and Dr. Pardo-Villamizar agreed that research on the microbiome and the immune system were areas likely to see increasing and needed attention in the future – particularly the potential role of fever. Ms. Redwood also said that the bigger picture was lacking. She said that it was important to know, not only how each system might contribute to the development of autism, but also how do the different systems interact, and how might that affect the development of autism.
Dr. Daniels explained the process for the upcoming Workshop.
Adjournment
The conference call was adjourned at 3:30 p.m.
Certification
I hereby certify that this meeting summary is accurate and complete.
/Susan Daniels/ November 15, 2013
Susan A. Daniels, Ph.D.
Executive Secretary, Interagency Autism Coordinating Committee
References
1 Ehninger D, Sano Y, de Vries PJ, et al. Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry 2012;17(1):62-70. [PMID: 21079609]
2 Braunschweig D, Krakowiak P, Duncanson P, et al. Autism-specific maternal autoantibodies recognize critical proteins in developing brain. Transl. Psychiatry. 2013 Jul;9(3)e277. [PMID: 23838888]
3 Bauman MD, Iosif AM, Ashwood P, et al. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl. Psychiatry. 2013 3e278. [PMID: 23838889]
4 Kato TA, Yamauchi Y, Horikawa H, et al. Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry. Curr Med Chem. 2013;20(3):331-44. [PMID: 23157624]
5 Levy D, Ronemus M, Yamrom B, et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron. 2011 Jun 9;70(5):886-97. [PMID: 21658582]
6 Di Martino A, Yan CG, Li Q, et al. The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Mol Psychiatry. 2013 Jun 18. Epub ahead of print. [PMID: 24093016]
7 Dawson G, Rogers S, Munson J, et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics. 2010 Jan;125(1):e17–23. [PMID: 19948568]
8 Boyd BA, Hume K, McBee MT, Comparative efficacy of LEAP, TEACCH and non-model-specific special education programs for preschoolers with autism spectrum disorders. J Autism Dev Disord. 2014 Feb;44(2):366-80. [PMID: 23812661]
9 Kasari C, Rotheram-Fuller E, Locke J, et al. Making the connection: randomized controlled trial of social skills at school for children with autism spectrum disorders. J Child Psychol Psychiatry. 2012 Apr;53(4):431-9. [PMID: 22118062]
10 García-Villamisar D, Hughes C. Supported employment improves cognitive performance in adults with Autism. J Intellect Disabil Res. 2007 Feb;51(Pt 2):142-50. [PMID: 17217478].
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Materials
- 2012 IACC Strategic Plan Update
- 2011 IACC Strategic Plan
- Compiled Objective Chart for Question 2 2008 to 2012 (PDF – 152 KB)
- Conclusions by Objective for Question 2 (PDF – 132 KB)
Conclusions by Objective for Question 2 (Biology)
Prepared for IACC Strategic Plan Update Question 2 Planning Group Conference Call November 8, 2013
| IACC Strategic Plan Objectives | Planning Group Summary | Funding 2008-2013 |
|---|---|---|
IACC Strategic Plan Objectives2.S.A. Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010 (Fever studies to be started by 2012). |
Planning Group SummaryThe recommended budget for this objective was met and many projects were funded in this area, but the field is still developing and emphasis on this objective should continue in the future. |
Funding 2008-2013$16,997,853 |
IACC Strategic Plan Objectives2.S.B. Launch three studies that specifically focus on the neurodevelopment of females with ASD, spanning basic to clinical research on sex differences by 2011. |
Planning Group SummaryThe recommended budget for this objective was partially met, and more than 3 studies were launched, but further work is needed in this area. |
Funding 2008-2013$5,856,783 |
IACC Strategic Plan Objectives2.S.C. Identify ways to increase awareness among the autism spectrum community of the potential value of brain and tissue donation to further basic research by 2011. |
Planning Group SummaryThe recommended budget for this objective has been partially met as of 2012. In 2013, NIH launched the NIH Neurobiobank ($5M), which includes samples for research on autism as well as other brain disorders, so this may not be reflected in the 2013 portfolio analysis figures. The NIH Neurobiobank has a web publication "Why Brain Donation? A Legacy of Hope." to increase awareness about brain donation. Loss of autism brain samples in 2012 due to a freezer malfunction has caused a loss of progress and there is a need for new samples to replace and build the amount of available brain tissue for ASD research. It was noted that some projects coded to this objective focus on tissue processing rather than specifically on donation. More funding and projects are needed to achieve this objective. |
Funding 2008-2013$856,031 |
IACC Strategic Plan Objectives2.S.D. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g., Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. |
Planning Group SummaryThe recommended budget for this objective has been met and a large number of projects funded that address this objective. Investment in this area has doubled since 2009, and there is an ACE center focused on tuberous sclerosis. This objective is on track. |
Funding 2008-2013$53,147,645 |
IACC Strategic Plan Objectives2.S.E. Launch three studies that target the underlying biological mechanisms of co-occurring conditions with autism, including seizures/epilepsy, sleep disorders, wandering/elopement behavior, and familial autoimmune disorders, by 2012. |
Planning Group SummaryThe recommended budget for this objective was met, and more than twenty projects were funded, but further efforts are needed, especially on wandering, metabolic and immune conditions related to ASD, as well as a systems-biology approach to understand how these co-occurring conditions are related to ASD. |
Funding 2008-2013$16,531,078 |
IACC Strategic Plan Objectives2.S.F. Launch two studies that focus on prospective characterization of children with reported regression to investigate potential risk factors by 2012. |
Planning Group SummaryThe recommended budget for this objective has been partially met. The number of recommended projects has been met, but further work is needed on comparing regressive autism to non-regressive autism. High-risk siblings may present an opportunity for studying regression prospectively. |
Funding 2008-2013$993,134 |
IACC Strategic Plan Objectives2.S.G. Support five studies that associate specific genotypes with functional or structural phenotypes, including behavioral and medical phenotypes (e.g., nonverbal individuals with ASD and those with cognitive impairments) by 2015. |
Planning Group SummaryThe recommended budget for this objective has been met, over 40 projects have been funded in this area, and the projects cover the areas described, so the objective appears to be on track. |
Funding 2008-2013$41,777,028 |
IACC Strategic Plan Objectives2.L.A. Complete a large-scale, multidisciplinary, collaborative project that longitudinally and comprehensively examines how the biological, clinical, and developmental profiles of individuals, with a special emphasis on females, youths, and adults with ASD, change over time as compared to typically developing people by 2020. |
Planning Group SummaryThe recommended budget for this objective was partially met and several projects have been funded in this area. More clinical studies are needed over a longer trajectory to identify issues faced as people with ASD age, especially with regard to risk factors for other medical conditions. |
Funding 2008-2013$20,690,241 |
IACC Strategic Plan Objectives2.L.B. Launch at least three studies that evaluate the applicability of ASD phenotype and/or biological signature findings for performing diagnosis, risk assessment, or clinical intervention by 2015. |
Planning Group SummaryThe recommended budget for this objective was partially met, and more than 3 studies were launched, but more funding and work in this area is needed. |
Funding 2008-2013$3,599,806 |
IACC Strategic Plan ObjectivesNot specific to any objective |
Planning Group Summary
|
Planning Group Summary$201,661,561 |
IACC Strategic Plan ObjectivesTotal funding for Question 2 |
Planning Group Summary
|
Funding 2008-2013$362,111,160 |
This document is for discussion purposes only and does not reflect the decisions of the IACC
Highlighting of each total gives an indication of the progress toward meeting the IACC recommended budget for each objective. Green highlighting indicates that funding fully meets the recommend budget. Yellow highlighting denotes that funding for a particular objective partially meets the IACC recommended budget, while red highlighting indicates that there has been no funding towards the particular objective.
blue text is an insertion
red text is a deletion
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Transcript
- Meeting Transcript (PDF – 197 KB)
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