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Autism Speaks to Sponsor “Autism Spectrum Disorders: From Genes to Targets to Treatments”

April 20, 2011 1 comment

Autism Speaks is proud to sponsor an upcoming New York Academy of Sciences Meeting entitled “Autism Spectrum Disorders: From Genes to Targets to Treatments.” Speakers will focus on emerging areas of research that are laying the foundation for development of novel therapeutics to treat autism spectrum disorders. The meeting will be held all day at the NYAS offices in NYC on April 29. For those that cannot attend in person, the organizer will be hosting a live interactive webinar.  Information about the meeting, the speakers and the agenda can be found at www.nyas.org/autism. Whether participating in person or via webinar, you need to register to ensure space and receive a link for the webinar. There is a small fee for attendance.

In addition, following the meeting, our sponsorship will allow for the creation of a podcast which summarizes the day’s talks and interviews the speakers for their impression of the day’s discussions. This will be made free of charge and provided on the NYAS website. Please stay tuned for the link to that podcast.

Turning Medical Science into Medical Treatments: The Quest for Translation in Phelan-McDermid Syndrome

March 19, 2011 24 comments

by Guest Blogger, Andrew Mitz, Ph.D.

The First International Phelan-McDermid Syndrome Foundation (PMSF) Symposium held earlier this month showed how a small parent-run organization can think and act big! With only 450 registered families worldwide and a mom at the helm, the PMSF put together a first class scientific meeting at the New York Academy of Medicine, by partnering with researchers from the Seaver Autism Center, Mt. Sinai School of Medicine. The goal of the meeting was to chart a course towards medical treatments for this rare, genetic cause of autism.  The theme of the meeting was scientific sharing, teamwork, and quality research.   Over two days (March 3rd and 4th), the participants heard from families and experts about Phelan-McDermid Syndrome, its history, its connection to autism spectrum disorders, and the very latest in scientific approaches. They also learned how people studying other disorders have found fast paths to drug development.

The early presentation by Dr. Catalina Betancur (INSERM, France) provided two key foundational scientific links to help open the meeting.  First, she showed that Phelan-McDermid Syndrome, also called 22q13 Deletion Syndrome, is one of many known genetic causes or risk factors of autism spectrum disorders.  Second, virtually all cases of chromosome 22 abnormalities that cause Phelan-McDermid Syndrome share damage to or loss of the SHANK3 gene as a common feature.  SHANK3 gene mutations are also found in about 1% of the general autism population. That is why understanding the biology of SHANK3, and how to treat the loss of SHANK3 in Phelan-McDermid Syndrome patients, resonated through every talk of the meeting.

The SHANK3 gene encodes a protein called Shank3 that is critical for proper synapse function. Synapses are the junctions or contact points between neurons of the brain, where information is exchanged. Thanks to the elegant and detailed descriptions provided by Dr. Tobias Boeckers (Ulm University, Germany), participants learned how Shank3 proteins stick to each other. The proteins form an interlocking network that acts as a backbone for the synapse both mechanically and chemically.  For this reason, Shank3 (also known as ProSAP2) is called a scaffolding protein.  Dr. Boeckers showed how the loss of Shank3 in Phelan-McDermid Syndrome makes the entire synaptic junction unstable. Shank3 is one of the first proteins required for synapse formation, which is constantly taking place in the brain. Dr. Carlo Sala (University of Milan, Italy), another pioneer in SHANK3 research, explained that proper synapse formation and stability are essential processes for learning and memory.

In a particularly memorable session on the first day, Dr. Boeckers and other investigators including Dr. Joseph Buxbaum (Mount Sinai School of Medicine), Dr. Craig Powell (University of Texas), and Dr. Yong-Hui Jiang (Duke University) shared details about their respective efforts to develop a Phelan-McDermid Syndrome mouse model with a mutated or deleted SHANK3 gene. The open and frank exchange resulted in a greater appreciation among the participants of the methodological challenges they share, and underscored how unfettered sharing of information can accelerate scientific progress as it helps reduce duplication and facilitates exploration of a greater range of possible solutions.  The families with Phelan-McDermid Syndrome looked on in great appreciation as the scientists ventured outside their normal comfort zone to openly share “intimate” (unpublished) details of their research.

Dr. Ricardo Dolmetsch (Stanford University) described his cutting-edge work on induced pluripotent stem cells (iPS cells).  He takes tiny skin samples from patients and, using a special protein cocktail, ”reprograms” them. The painstaking process takes many months to first produce stem cells, and then neurons. Amazingly, Dr. Dolmetsch showed that these neurons behave much like the neurons studied in animal models, which validates both his work and the animal models.  With his iPS-generated neurons in hand, Dr. Dolmetsch plans to test compounds to see which ones are most effective in reversing the deficits seen in these cells.

Dr. Sala studies animal neurons using another experimental approach called “knockdown”.  He simulates what happens in Phelan-McDermid Syndrome patients missing one of their SHANK3 genes by interfering with the production of Shank3 protein.  When Shank3 is knocked down, Dr. Sala noticed a reduction in a receptor called mGluR5. This receptor is normally active during communication between neurons. mGluR5 mobilizes other signaling molecules, gene expression and production of other synaptic proteins. Dr. Sala showed that it is possible to partially restore much of these functions by applying a drug that stimulates the remaining mGluR5 receptors and activates related molecular pathways. This work is vital for identifying potential biological targets for drug development.

In the quest for a quick and efficient path to new therapeutics, Dr.Ozlem Bozdagi Gunal (Mount Sinai School of Medicine) presented exciting new results. Using “knockout” mice missing one SHANK3 gene, she looked to see what known drugs could correct at least some of the synaptic defects. She showed that the structural defects in the synapse lead to failures in the way it functions, especially during learning. The research team identified a drug that allows a particular well-studied form of synaptic strengthening, called long term potentiation, to proceed normally in spite of deficits in Shank3.

Everyone’s eyes and ears were on Dr. Mark Bear (MIT) as he described his groundbreaking work to find treatments for Fragile X Syndrome, another single gene disorder that, like PMS, can cause autism. He brought hard-learned lessons from his translational efforts. He explained that the quickest road to therapeutics requires a detailed understanding of the underlying pathophysiology (disease mechanism), and robust animal and cell model systems for screening and evaluating promising candidate drugs. He emphasized information sharing and the importance of high quality science.
Dr. Roberto Tuchman, the director of the Autism Program at Miami Children’s Hospital Dan Marino Center spoke on the clinical overlap between epilepsy and autism. He explained that epilepsy, when it starts early in life, is a developmental disorder of the brain with similar pathophysiology to autism. He suggested that early detection and treatment of epilepsy is an important way to ensure optimal brain development. Likewise, early detection and treatment of autism could be just as valuable. Dr. Tuchman highlighted new developments in the early behavioral treatment for autism and suggested that these treatments could be effective for all early onset neurodevelopmental disorders in which there is an atypical developmental trajectory. He favors treating at-risk children rather than waiting for a diagnosis of autism or autism spectrum disorder.  By waiting, the window of opportunity to protect development may narrow. He raised the possibility that new drug interventions targeting synaptic pathways common to both epilepsy and autism hold significant promise for disorders such as Phelan-Mcdermid syndrome, in which autism and epilepsy commonly co-exist.
In the final session of the symposium, participants divided into three workgroups.  These breakout sessions hosted lively discussions among family members, clinicians, researchers, and other advocates. These workgroups leveraged topics and ideas discussed earlier in the symposium, with particular attention paid to (1) how the Phelan-McDermid Syndrome patient registry can best meet the needs of its many stakeholders, (2) how clinical research and care guidelines for Phelan-McDermid Syndrome can be advanced, and (3) how the patient advocacy community can help to accelerate translational efforts related to Phelan-McDermid Syndrome.  The breakout sessions proved to be an effective means of engaging all participants to work collaboratively in determining the future directions of PMSF’s research support initiatives.  There is no question that everyone left the meetings with a heightened sense of partnership towards an urgent goal.


The power of words: The IACC works to reconcile different perspectives on autism

January 20, 2011 9 comments

This guest post is by Geri Dawson, Ph.D., CSO, Autism Speaks.

The task of this week’s meeting of the Interagency Autism Coordinating Committee (IACC) in Rockville, Md. was to approve an update to the IACC’s Strategic Plan for Autism Research. Most of the updated sections had been approved at earlier meetings, but the committee still had to grapple with the introduction, which contained several sticky phrases. The committee is a diverse group of people ranging from a parent who believes that autism is the result of injury caused by toxins in our environment to an adult on the spectrum who views autism as a natural part of our human diversity. Given the wide range of perspectives, words matter a lot.

For example, the committee all agreed that the plan should convey a sense of urgency. Autism represents a serious public health crisis and immediate action is required. So far so good. But how should the plan convey that sense of urgency?  As the discussion began, a lively debate ensued about a proposed revision to the plan’s opening paragraph, which was adapted from the Autism Speaks’ website:

Today, autism is more common than childhood cancer, juvenile diabetes and pediatric AIDS combined, and the increasing numbers of children being diagnosed with autism has created a national health emergency. In a September 30, 2009 speech at the National Institutes of Health, President Obama specifically cited autism, along with cancer and heart disease, as one of three health conditions targeted for major scientific research investment through the American Recovery and Reinvestment Act. The President expressed his hope that research into genetic and environmental factors would result in strides in early intervention, treatments and therapies to help people affected by autism achieve their fullest potential (hot button words bolded).

The words that some members were concerned about were “childhood cancer, juvenile diabetes and pediatric AIDS.” They objected to the notion of comparing autism to diseases such as these and felt such a comparison was disrespectful to people with autism. After all, autism is not a terminal disease like cancer, one person pointed out. Others noted that the comparison was meant only to convey the scale of the problem, not to imply that autism was a terminal disease. They said that the comparison was meant to convey the huge number of people who are affected by autism. The discussion continued until Tom Insel finally pointed out that the committee had spent 30 minutes discussing the first sentence of the plan, and we still had a lot of work to do. A vote was then taken and the revision was adopted.

Similar issues were raised about the following passage, which was part of last year’s document:

The cost of ASD to affected people, families, and society is enormous. A great majority of adults with ASD struggle with ongoing and mostly unmet needs for employment, housing, services, and supports. Compounding these stressors, families with a child with autism typically lose income, possibly as a result of one parent leaving the workforce in order to care for and meet the special health and educational needs of the child. The cost to society of ASD is currently estimated to be $35-$90 billion annually, the higher estimate being comparable to Alzheimer’s disease (hot button words bolded).

Again, some committee members asked whether we should we compare ASD to Alzheimer’s disease and asked what kind of message we send to people with autism when we characterize autism as a “burden to society?” This passage could be alienating to parts of the autism community, it was pointed out. Other committee members argued that people should be made aware that families do carry a substantial burden, both financially and emotionally, especially when these families don’t have adequate services and interventions. They noted that it is important to know how much autism costs society, as this helps justify the need to increase our investment in developing better interventions. By a slimmer margin, a committee vote kept this passage in.

Less controversial but still garnering substantial discussion was the proposal to add a cross-cutting theme on the ethical, legal and social implications of autism research. The proposed language was:

As more progress is made in the autism research arena, new ethical, legal and social implications of ASD research will need to be considered and taken into account by researchers and consumers of research findings. In particular, genetic research poses unique ethical risks that require consideration both within research projects focused on other questions and in efforts dedicated specifically to exploring these ethical challenges and the appropriate responses to them. As such efforts are undertaken, it is critically important to include the autistic adult community, family members of individuals on the autism spectrum and other stakeholder groups within the discussion (hot button words bolded).

The committee was in unanimous agreement that studying the ethical issues associated with autism research is very important. At an earlier IACC meeting, I had proposed adding a research objective to this effect. The committee decided, however, that virtually all research on autism poses ethical risks and benefits, whether that research is on genetics, early screening or interventions. Furthermore, it was decided that, whenever possible, all people with autism, not just adults, should be part of the discussion about the potential risks and benefits of research.

Finally, the committee struggled with whether to add another new cross-cutting theme, one focused on self-determination. Self-determination refers to the ability to consider options and make appropriate choices regarding where to live, work, and spend one’s leisure time. Although in theory and spirit most people on the committee agreed with this concept, some expressed the concern that it was unrealistic to expect a severely impaired person with autism to live a self-determined life. “Could we perhaps substitute the phrase ‘supported self-determination,’” one committee member asked. When consensus wasn’t easily reached, the committee entertained deferring the decision until they had more time to deliberate and understand the implications of adding such language to the strategic plan. Finally, however, a vote was taken and the proposal to include the cross-cutting theme of self-determination was adopted by a slim margin.

Unlike some other committee members, I felt confident that adding a cross-cutting theme on self-determination would strengthen the strategic plan and argued strongly for its inclusion. As a clinician who has worked for years with people with autism of all ages, including those who are severely affected, I have witnessed the power and success of empowering all people with ASD with self-determination. This begins early on with teaching young children with ASD how they can effectively express their needs, wants and preferences. By doing so, such a child will have stronger self-esteem and be happier, more motivated to learn, and more likely to succeed. A study of two types of applied behavior analysis, one in which the goal and reward was chosen by the therapist and another in which they were chosen by the child with ASD, found that allowing children to make choices and work with preferred materials resulted in more highly motivated children and faster learning rates. Similarly, I have worked with severely affected nonverbal adults whose only option for expressing their dissatisfaction with their lives was to become aggressive or noncompliant. Offering these adults appropriate choices and control over how they wanted to spend their work and leisure time allowed them to live happier, more productive lives with little need for disruptive behavior.

There is often the misperception that self-determination means that a person is entirely autonomous or independent. All of us are dependent on others, and none of us is entirely autonomous. However, expressing one’s preferences, making choices, and having a sense of control over one’s life is not only a human right, it is an inherent part of being a healthy, happy human being.

I left the meeting feeling that the IACC has come a long way. Although there was disagreement among its members and people felt passionately about their positions, people treated each other with respect. Unlike the stalemate we are witnessing in our federal government with parties strongly entrenched and unwilling to “reach across the aisle,” committee members were more flexible with different subgroups of people coalesced around different positions. It was clear that, although we each come from a different perspective, we are all working toward a common cause:  improving the lives of people with autism and their families. Working together, rather than against, each other can only accelerate our efforts toward this common goal.

For more information on the Interagency Autism Coordinating Committee visit here.

Feeling exposed? Insights from a new meeting on environmental impacts in autism

December 11, 2010 10 comments

by Sallie Bernard, Autism Speaks’ Board Member, co-founder and Executive Director of Safe Minds

Given the historic inattention of the scientific establishment to the environmental contributions to autism, it was nice to see a day-long conference on the topic held this week by a major research center. “Exploring the Environmental Causes of Autism and Learning Disabilities” was put together by the Children’s Center for Environmental Health at the Mount Sinai School of Medicine in New York City. The center is run by Dr. Phil Landrigan, who has been a prominent researcher on the harmful effects of environmental toxicants for decades. He told the incredible story of the harms of lead exposure on children’s cognition and behavior, and how the successful effort to remove leaded gasoline from the market in the 1970s resulted in rising IQ scores and economic gain to the country. I hope this same massive effort will be applied to autism and the chemicals which underlie the increase in its prevalence.

Also of note was the presence at the meeting of Linda Birnbaum. Dr. Birnbaum is the director of the National Institute of Environmental Health Sciences (NIEHS) which holds the autism/environment portfolio at NIH. The Mt. Sinai meeting follows on a workshop held at NIEHS several months ago which explored the role of the environment in autism. Large scientific initiatives in the field fall to the NIH, so without its support, gains will be painfully slow. Hopefully Dr. Birnbaum’s personal involvement signals a heightened interest at NIEHS to look at autism. Although Dr. Birnbaum stated at the conference that her institute spends $30 million on children’s environmental health, at a Senate hearing earlier this year, it was shown that just $8 million of this is for autism specifically.

A few interesting bits of information came out of the conference. One was the definition of “environment” that the insiders use. It covers synthetic chemicals like pesticides, flame retardants and plasticizers; heavy metals like arsenic, lead and mercury; combustion and industrial by-products; diet and nutrients; medications, medical interventions, and substance abuse; infections; the microbiome; heat and radiation; and lifestyle factors. Some may be harmful; others protective. They may operate before conception, during pregnancy or in early life, and some may alter gene expression through epigenetic modifications to chemicals surrounding our genes. Craig Newshaffer, who runs the EARLI study to look at environmental factors among younger autism siblings, referred to the concept of the “exposome”, that is, everything we are exposed to and its effects on health. Dr. Birnbaum’ made the point that health does not equal medicine, and prevention through reduction in chemical exposures is of equal importance to health. Colleen Boyle from the CDC stated that the next prevalence report will be issued in April 2011. We will see if the 1 in 110 number from last year’s report has changed. New research from Korea was unable to confirm increased risk of autism due to parental age or low birth weight, which have been identified as risk factors in Western studies.

The most informative talk was by Dr. Irva Hertz-Picciotto from UC-Davis. She explained how changes in diagnosis do not account for most of the increase in autism rates, and how recent research by their group on mercury and flame retardant blood levels do not address whether these substances are causative for autism because the blood samples were taken years after the autism diagnosis. A paper out this week from UC-Davis found that proximity to traffic air pollution during pregnancy almost doubles the risk of autism. Another paper just accepted by a journal has found higher antibodies to cerebellar tissue in children with autism relative to controls, highlighting the immune component in autism.

Other than these interesting items, the conference covered minimal new ground as far as the science goes. Rather, the points of the meeting seemed to be to make the case that environmental factors research in autism must now be considered mainstream science and to showcase the work being done or about to be done to investigate the issue. Dr. Landrigan made the case for an environmental role by noting that the rate of autism has increased too much to be solely genetic, and that at most, genetics alone will end up explaining 40% of autism cases with the likely percentage much lower.

Autism Speaks provided funding for the conference so that families could attend for free. Alycia Halladay, who runs our environmental science portfolio, noted that environmental factors and how they interact with genetics became one of Autism Speaks 5 priority areas for science in 2010. Autism Speaks also co-funded the NIEHS workshop on the environment earlier this year. Mt. Sinai plans to make video excerpts of the conference available in a few weeks.

Read more about this meeting in The Daily Green.

Common language: Exploring community collaboration in the translation of genetics discoveries

September 13, 2010 3 comments

The past several years have seen significant advances in our understanding of the genetics of autism spectrum disorders (ASD). As result, many researchers and companies have begun exploring the possibilities of translating these discoveries into clinical applications, especially those that could help with diagnosis. By detecting and understanding genetic risk factors for autism, it is possible to  provide earlier diagnosis and intervention, which typically leads to better outcomes.  In addition, it can help identify subgroups within our community, that because of shared risk factors, may benefit from more targeted or specific treatment.  Finally, some genetic etiologies are associated with specific medical conditions, such as seizures, cancer, and GI problems.  Thus, information about specific genetic etiologies can have significant clinical implications. Using this kind of approach, it may also be possible to identify individuals who are predisposed to particular environmental risk factors and help improve our understanding of the role of gene-environment interactions in autism.

Most importantly, Autism Speaks is interested in encouraging the development of real world solutions that can help families make more informed healthcare decisions and improve their overall quality of life. While it has long been known that autism involves genetic factors and genetic testing is already being conducted for some genetic etiologies, such as Fragile X syndrome, recent studies have identified many other autism risk genes that are not routinely screened for during a diagnostic exam.  Including more comprehensive genetic screening could be of real benefit to persons with ASD.  However, we recognize that the science is still evolving, and there are many uncertainties and important issues such as ethics and risk communication that must be carefully weighed and considered to maximize potential benefits to individuals as well as families in our community.

In order to better understand the state of the science and opportunities and barriers in translating autism genetics discoveries into diagnostic tests, Autism Speaks and several partners, including the National Institutes of Health (NIH), Canadian Institutes for Health Research (CIHR), and the UK’s Medical Research Council (MRC), organized an educational symposium, “Genetic Risk Factors for Autism Spectrum Disorders: Translating Genetic Discoveries into Diagnostics,” in Toronto, Canada, on September 1-2, 2010.  By bringing together a multidisciplinary group of about 80 international experts and stakeholders, including government officials, funding agencies, scientists, clinicians, ethicists, lawyers, biotech companies, parents and self-advocates, the symposium aimed to develop some consensus around two key questions: (1) Is the science ready for translation of genetic findings to clinical diagnostics? And if so, (2) how can the professional and stakeholder communities work best together to ensure that genetic diagnostic testing is a benefit to persons with ASD?

With an audience as diverse as the one at this symposium, a variety of opinions was expected. Some researchers thought this discussion was a bit premature because the science is still evolving and the interpretation of microarray-based clinical genetics findings can be oftentimes be complicated. Others, however, advocated for a cautious but firm push to help families by establishing an authoritative reference database and clarifying regulatory guidelines. Developing guidelines for the use of interpretation of genetic testing is especially important since several companies are already providing genetics testing services for the medical community.  The FDA acknowledged the new terrain, but clearly preferred greater oversight to help protect consumers. Medical geneticists and genetic counselors pushed back that more regulations may not be necessary because of the professionals’ well-established track record in helping individuals and families interpret and understand complicated genetic findings.  Bioethicists and communications experts left the attendees more appreciative of important non-technical issues that should be a part of any deliberation on the risks and benefits of genetic diagnostics for autism. Parents and self-advocates, while optimistic about the promise of the technology, also highlighted the need to address the implications of this technology on important community issues about identity and choice [Read John Elder Robison’s blog on this topic in Psychology Today].

After a packed and intense one and a half days, including breakout sessions where many vigorous and fascinating discussions ranged from community impact to next generation of diagnostic devices, the participants achieved consensus on several important issues, the details of which will be published via a peer reviewed journal and other dissemination channels in the near future. Suffice to say, while there was a general appreciation for how much work we still need to do, there was also enthusiasm for an opportunity to work together to help individuals and families benefit from the translation of latest genetics discoveries.

Categories: Science Tags: , , ,

Community partnerships for research and solutions

April 29, 2010 2 comments

This post is by Leanne Chukoskie, Ph.D. Dr. Chukoskie is the Asst. Director Science Communication and Special Projects at Autism Speaks and Asst. Project Scientist, Institute for Neural Computation, UCSD.

Having not previously interacted with the National Institutes of Environmental Health Sciences (NIEHS), I didn’t know what to expect.  I must admit a tendency to equate the National Institutes of Health with the pinnacle of ivory tower research and a somewhat “stuffy” perspective on science. I could not have been more off base in describing the inaugural meeting of the Partners in Environmental Public Health (PEPH).

The initiative aims to bring together academia and community stakeholders as partners in improving environmental health, and this was clearly a charge that the leadership and participants took seriously (read a description of the meeting).  The passion of the people participating in this meeting was palpable. Many of the community organizers and research partners in attendance have been seeking solutions for local environmental problems for years. Spontaneous applause and whoops from the audience erupted in response to community-empowering comments or discussion. This wasn’t your typical scientific conference! After each discussion session, the moderators had to actively intervene to end the questions and suggest that the conversation continue over the next break, lest we get horribly off our time schedule.

At the meeting my colleague, Alycia Halladay, and I conversed with other public health advocates about what we and other organizations are doing to disseminate research findings to members of the community. How were we learning what issues concern the community most? How do we use that information to address those concerns? How are we delivering scientific information about autism to the public and are they “getting it”? These other groups wanted to learn from us, and we from them.

We learned about an exceptional program that trained portreros (trusted communicators in the local Hispanic community) in various aspects of environmental science understanding using hands-on science demonstrations. The portreros then met with other members of their community to convey needed information about local environmental risks surrounding a superfund clean-up site. Could we develop the resources to train our team of volunteer Science Ambassadors at Autism Speaks similarly?

We also heard an important presentation from Michael Yudell, Ph.D., M.P.H. of Drexel University who spoke about communicating autism research findings to the public in a clear, direct and useful manner. Citing the history of how “blame” has been used by different ways and different groups to identify the causes of autism, Dr. Yudell offered recommendations for improving the dissemination of research  based on a meeting organized at Drexel last year

It is in meetings like this is where the rubber meets the road.  There are so many areas of opportunity for autism, which is one of NIEHS’ priority areas of investigation, including opportunities for organizations and other community advocates to partner with academia and apply for grants. Most importantly, however, this initiative enjoys ongoing support from the government.. We look forward to making the most of the opportunities offered and working with you, the autism community, to make the changes we need most.

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