This guest post is by Nancy Jones, Ph.D, the Program Director for the Autism Treatment Network and Autism Clinical Trials Network at Autism Speaks.
Developing novel and more effective treatments that improve quality of life for individuals with autism is a great need but also a substantial challenge. The challenge is not only to discover treatments but also to support their efficacy with evidence from rigorous treatment trials.
There is a large body of research showing that a wide range of behavioral interventions are safe and effective for improving cognitive and language abilities and adaptive behavior in children with ASD. Many people with ASD can receive additional benefit from the use of medicines, but the medications that are currently available, tend only to address symptoms associated with ASD, such as irritability and hyperactivity. While important, there is a great need to develop medications that can help reduce the core symptoms of ASD, including difficulties in social interaction and communication and repetitive behaviors. To accelerate progress in this area, this year, Autism Speaks launched a Translational Medicine Research Initiative. Its overarching goal is to increase the number of safe and effective medical treatments available for individuals with ASD.
One may wonder why the development of new treatments is such a challenging task. One challenge is getting all of the different stakeholders needed to accomplish this goal together and working collaboratively by sharing resources and ideas. This means bringing together the academic scientists who are making basic discoveries about autism, the clinicians treating children and conducting the clinical trials, private and public funders who provide research grants, the companies that develop pharmaceutical and nutritional treatments and the families and individuals with ASD. To achieve this, one of the first endeavors of Autism Speaks’ Translational Research Initiative was to host two meetings bringing together these key stakeholders. These meetings launched the initiative and set the stage for further directions and activities.
One barrier to the development of effective treatments has been the tremendous individual differences found across individuals with ASD in terms of their symptoms and needs. This raises two important questions: 1) How do we best identify the individuals who will be most responsive to specific treatment, and 2) What is the best way to measure that a treatment has actually had an effect? These questions are concerned with “outcome measures” – the assessments that are used to determine whether a treatment has been effective. Outcome measures were the focus of the first meeting, Outcome Measures for Clinical Trials with Individuals with ASD: Challenges and Opportunities, co-sponsored by Autism Speaks and Pfizer, Inc., held in Washington DC on Jan. 11-12, 2011. The meeting hosted clinicians, academic experts in the field of outcome measurement, representatives from eight pharmaceutical companies, funding agencies, and community stakeholders. The meeting’s goals were: 1) to discuss strategies for promoting more effective clinical trials of medications to address autism core and associated symptoms and 2)to develop consensus regarding the best clinical assessments to determine whether a treatment has been effective in clinical trials.
The group discussed the following key points to be addressed in future initiatives:
- Since there are currently a number of very good outcome measures that are appropriate for clinical trials,developing consensus on a group of standard measures is a key next step. FDA approval of a medication requires consensus outcome measures. Among the questions that were discussed in regards to standard measures were: 1) what are the most sensitive outcome measures, 2) what is the best setting to measure outcome, and 3) from whom should the outcome data be collected (parents, teachers, clinicians)?
- There are opportunities to develop new outcome measures based on promising technologies that provide measures of biological change. Experts in new technologies that can make use of devices such as the iPhone to collect outcome data in real time and in real world settings also offered several promising ideas.
- Long-term success of those conducting clinical trials with people with ASD requires closer collaboration between parents, clinicians, and the basic scientists who are developing treatment targets.
The second meeting was focused on the basic science that is aimed at developing new treatment targets. Translational Medicine Research in ASD: Challenges and Opportunities, was held January 25-27, 2011 in Santa Monica, CA. The goal of this meeting was to identify ways to accelerate the basic science needed to discover and develop new medicines. The meeting included a cross-section of leaders from research funding agencies and the pharmaceutical industry, as well as experts in the fields of molecular biology, neuroscience, animal models, metabolism, and clinical research. Topics ranged from single gene disorders to medical conditions such as GI problems, epilepsy, and mitochondrial disorder, to assays for screening medications, such as induced pluripotent stem cells.
The discussion and presentations addressed three key issues: 1) What have we learned from drug discovery in other disorders that can help us develop novel autism treatments? 2) What does autism biology tell us about promising systems and pathways that might be amenable to treatment? 3) What is needed to take promising ideas from the lab and speed their development into effective treatments?
A number of key points were highlighted, including:
- Private and public partnerships involving non-profit organizations, NIH, and industry will be critical for providing the supportive environment to move discovery forward. Partnerships with industry, in particular, are crucial since these companies are responsible for bringing medications to market. These partnerships are necessary not just for funding opportunities, but also for the creation of research collaborations and shared resources, such as biorepositories and databases.
- New findings in the areas of genetics and neuroscience are helping us better understand the biology of ASD and are pointing toward the development of new treatments. Some new treatments are already in the pipeline and others are being studied. Continued investments in understanding the underlying physiology and biology of ASD are crucial for making continued progress in this area.
- The discovery of new therapeutics for ASD can take advantage of what has been learned from related single gene disorders such as Rett Syndrome, Fragile X and Tuberous Sclerosis. Because we know so much more about the biology of these conditions, drugs targets and in some cases, human clinical trials are already developed for these conditions. Will some of these medications also be useful for the larger population of individuals with ASD?
- New technologies exist for understanding the biology of ASD and testing novel therapeutics that were not previously available. The hope is that these technologies will accelerate discovery.
- Individuals with ASD and their families can provide vital information about their experience with treatments and their treatment needs to prioritize future research investments. Progress will depend on families and scientists working closely together.
Many families and individuals with ASD have been awaiting the development of novel treatment options. A clear message from both these meetings is that we are at a place where we have knowledge, promising technologies, and most importantly, the interest and commitment amongst key stakeholders to be successful in this pursuit.