Science advances in fits and starts. Part of Autism Speaks’ role as an advocacy and science funding organization is to find ways to identify and advance the science that could lead to improvements in the lives of those struggling with Autism Spectrum Disorders. New ideas bubble up frequently, however few mechanisms exist to support the exploration of unique and novel ideas. The burden of evidence required to secure funding for a great idea is very high and often dissuades researchers from pushing for greater innovation and out-of-the-box thinking, resulting in research that is “safe” and moving at a pace that is slower than any of us would like.
To address this need, Autism Speaks has launched the Suzanne and Bob Wright Trailblazer Awards. The Trailblazer Awards commemorate Autism Speaks’ fifth anniversary and honors our organization’s pioneering founders, Suzanne and Bob Wright. We are grateful to the generous donors who have made contributions to support this special research innovation fund.
Trailblazer Awards provide seed funding to test out a novel idea or approach that has the potential to transform some aspect of autism research. Importantly, applications for these awards are accepted and reviewed on a rolling basis so new ideas are evaluated quickly and those ripe for this mechanism meet with funding quickly. The three funded projects summarized below will receive up to $100,000 for one year and each addresses a point of need as outlined in Autism Speaks’ Strategic Plan.
Mitochondria have been the focus of considerable buzz in autism research recently. However, the reports on mitochondria’s control of cellular energy processes only scratch the surface of the complex web of cellular activities that these organelles orchestrate [see also mitochondrial and fever story]. Robert Naviaux, MD., Ph.D., (UCSD) and his colleagues are grateful for the opportunity to pursue research on how mitochondrial metabolites may play a role in brain inflammation. “The Trailblazer award gives our lab the support to bring together 3 world-class groups to study the role of mitochondria in autism. If successful, our results will provide the foundation for both fresh new therapies, but also for additional studies that clarify the role of mitochondria and the environment in the cause of autism,” said Naviaux.
The idea Dr. Naviaux brought to Autism Speaks focuses on a product of the mitochondria, called ATP, that is required for the development of brain cells and their communication with each other. For cells to function properly, very specific quantities of ATP are required around the brain cells. Naviaux will explore whether mitochondrial dysfunction, which can result in high concentrations of ATP in the space between cells, stimulates inflammation in the brain, and also alters connectivity between neurons. Importantly, Dr. Naviaux and his colleagues will also test a compound that works against the effects of high concentrations of ATP as a potential therapy. The effects of manipulating ATP and the pathways it tickles will be tested in a well-established mouse model for autism so the effects at both the cellular as well as behavior level can be compared before and after treatment. Read the grant abstract.
Phil Schwartz, Ph.D. (Children’s Hospital of Orange County) is building a unique resource that aims to bring personalized medical solutions to individuals living with autism. The technology now exists to take a small sample of skin tissue and from that create stem cells that can be used to make personalized copies of any type of cell in the body. Of interest to autism, of course, are brain cells. Schwartz and his colleagues have not only created neurons from skin cells, but they are also pioneering a method to incorporate them into living mouse brains so they can evaluate how these human-derived cells function as part of a circuit. Dr. Schwartz is extremely enthusiastic about this research, saying “If this research is successful, we will be able to test, in animal model of autism based on human cells, novel therapeutic approaches and examine those putative therapies on bona fide human cells in an in vivo setting. This is about as close as we can get to clinical trials without actually using humans!”
Dr. Schwartz and his colleague, Dr. Diane O’Dowd, are aiming to build the largest bank of stem cells made from skin (called induced pluripotent stem cells) for autism research. If these new techniques prove successful, there will be a unique new tool for individualizing autism research unlike any currently available today. Read the grant abstract.
Earlier this year, Antonio Persico, M.D. (Università Campus Bio-Medico di Roma) published results demonstrating that a class of viruses, called polyomaviruses, were found significantly more often in postmortem brain tissue of persons with ASD than in individuals with typical development. The presence of these viruses presents a possible mechanism for the persistent immune activation seen in brain tissue of individuals with autism, originally reported by Vargas and colleagues in 2005. How did the viruses get into the brains of these people and what does this mean? Dr. Persico thinks that at least some forms of autism can be explained by the passing of a virus “vertically”, that is from parent to child, by incorporating itself into the genetic material in the sperm or egg. The presence of this virus is unknown to the carrier without explicit testing (ie. these individuals do not appear to be acutely ill) and can remain quietly.
Polyomaviruses have been shown to cause autoimmune disorders, which have been correlated with the first degree relatives of individuals with autism. If an early and unresolved polyomavirus infection was present in children with autism, the researchers would expect to see evidence of persistent immune activation for these viruses outside the central nervous system. Indeed, children with autism had lower levels of certain types of polyomavirus in urine than did typically-developing children. These polyomaviruses result in common childhood infections and low levels of virus in children with autism is indirect evidence for immune activation against these specific viruses. This clue led Dr. Persico and his colleagues to hypothesize that polyomavirus was likely passed from a parent and not acquired later in life. “What is transmitted from parent to offspring may not be human DNA but rather a virus. This idea could explain high heritability as well as systemic signs and symptoms of ASD, such as overgrowth of the entire body, immune and biochemical abnormalities. The translational potential of this project in terms of diagnostics, prevention and therapeutics is self-evident,” says Persico. Read the grant abstract.
Taken together, these new grants and the Trailblazer funding mechanism represent a bold new effort to attract and support the most innovative ideas that have the potential to transform our understanding of autism research. We anxious await to hear from each of these researchers to learn what they discover.
Read a press release about all of the science grants announced by Autism Speaks in December 2010.
Reference: Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67-81. Erratum in: Ann Neurol. 2005 Feb;57(2):304.