Posts Tagged ‘translational research’

How common are anxiety disorders in people with autism, and are there effective treatments?

January 6, 2012 14 comments

This week’s “Got Questions” answer comes from Rob Ring, PhD, Autism Speaks vice president of translational research.

Without question, anxiety is a real and serious problem for many people on the autism spectrum. We hear this from parents, teachers and doctors, as well as from adolescents and adults with autism spectrum disorder (ASD). This disabling anxiety can take the form of one or more disorders, including panic disorder and phobias.

A recent review of scientific studies on autism and anxiety revealed that we have no clear gauge of how commonly anxiety disorders overlap with autism. A few small, relatively short-term studies have produced starkly different results: from 11 percent to 84 percent. (For comparison, the prevalence of anxiety disorders among the general population is about 18 percent.) A reliable estimate will require a study that tracks many more individuals with autism over longer periods of time and that considers the distinctive way that anxiety oftentimes expresses itself in those affected by ASD.

Fortunately, Autism Speaks is funding the Autism Treatment Network, which collects systematic data on a wide range of medical conditions, including anxiety disorders, in children with ASD.  This data will help us better understand the proportion of people with ASD who are suffering from anxiety symptoms.

Meanwhile preliminary studies have provided insights. They suggest, for example, that adolescents with autism may be particularly prone to anxiety disorders, while younger children on the spectrum may not differ at all from the average population. Some studies likewise suggest that high-functioning individuals on the spectrum experience higher rates of anxiety disorders than do lower-functioning individuals. Still we must emphasize that these results are preliminary. We don’t know nearly as much as we should about how anxiety disorders affect those with autism.

recent review of studies found that behavioral interventions can help many children and adolescents with autism who also struggle with anxiety. Along these lines, some studies  suggest that cognitive behavioral therapy can be particularly helpful for high-functioning adolescents and adults with autism and anxiety. We will explore behavioral interventions further in a future “Got Questions?” blog. My own expertise is in the medical treatment of anxiety in persons with ASD.

Currently, we have no medications approved by the Food and Drug Administration (FDA) expressly for the treatment of anxiety in children, adolescents or adults with autism. Some classes of drugs commonly prescribed for treating anxiety disorders in the general population likewise help some of those on the autism spectrum. These include the selective serotonin reuptake inhibitors (SSRIs) such as Prozac. For those with autism, anxiety drugs are best used in combination with behavioral interventions. Among high-functioning individuals, they may be particularly effective when combined with cognitive behavioral therapy.

However, some doctors report that anti-anxiety medications seem to be less effective overall in people with autism spectrum disorder than they are in the general population. This observation needs to be verified with controlled research. It suggests the possibility that the biological root of anxiety in those with autism may differ from the “norm” and, as a result, may respond best to different treatments.

At Autism Speaks, we are actively supporting research into anxiety disorders and other medical conditions frequently associated with autism. This includes both basic research on the underlying biology of autism and the safe development of drugs that can relieve disabling symptoms and improve quality of life.

If you are considering anti-anxiety medication for a child with autism, our recently published Medication Decision Aid can help you work with your child’s physician to sort through the pros and cons in the context of your values and goals for your child. You can learn more about the medication tool kit and download a free copy, here.

Got more questions? Send them to And bring them to  our next webchat with Autism Speaks Chief Science Officer Geri Dawson, Ph.D., and  Autism Speaks assistant vice president and head of medical research Joe Horrigan, M.D. More information on their monthly webchats here.

Light Provides Insight

August 9, 2011 5 comments

Posted by Rob Ring, PhD, vice president of translational research for Autism Speaks


This week a reporter from Bloomberg News asked me to comment on new research showing how stimulating certain brain cells can spur autism-like symptoms–and how calming these same cells can restore normal behavior. The reporter quoted me as calling the research “revolutionary.” It’s true—for a number of reasons.

We need to study brain activity to better understand and treat social behavior disturbances such as those associated with autism. Researchers do this by seeing what happens when they change what’s happening in the brain. But until now they’ve had only crude methods such as administering chemicals that target many parts of the brain.

To better understand normal and altered brain activity, we need to pinpoint exactly where something is going wrong. It helps to think of brain cells and their connections as microcircuits. Following this analogy, researchers need to be able to test specific microcircuits within the brain.

With this in mind, Karl Deisseroth and his colleagues at Stanford University used genetic engineering to create mice that produce brain chemicals that are activated by light. When activated, these chemicals excite surrounding brain cells. The researchers then used tiny pulses of laser light to produce activity in specific parts of the brain—right down to the level of a few brain cells, or a specific brain circuit.

Using this approach, the researchers found that when they stimulated certain cells in the prefrontal cortex—a part of the brain involved in social behavior—the mice stopped socializing with each other. At the same time, the mice’s brain waves took on a pattern seen in many persons with autism. Then, the researchers used a different light that dampened the activity and calmed the overexcited cells. In response, the mice started socializing again and the autism-like brain waves began to disappear.

The idea here isn’t to control behavior or implant fiber optics in anyone’s brain! What Karl has developed is a way to help us see exactly where something might be going wrong inside a brain and decipher exactly what is happening there.

Importantly this kind of approach may allow us to use lab animals to test new medicines that can help “rebalance” certain brain circuits to ease autism symptoms–and do so with fewer or no side effects.

This is the kind of pioneering research that wins the Nobel Prize. Even more important, we at Autism Speaks want to be supporting research along this promising path toward greater understanding of autism, its prevention and its treatment.

On the Cutting Edge of Treatment and Technology

July 15, 2011 14 comments

Posted by Rob Ring, PhD, vice president of translational research for Autism Speaks

Translational research in autism converts complex scientific discoveries into  real life benefits for those living with autism spectrum disorders (ASDs). Earlier this year, I had the privilege of organizing and moderating a translational research symposium we called “Autism Spectrum Disorders: From Genes to Targets to Treatments” at the New York Academy of Sciences. The symposium was made possible through funding from Autism Speaks. Indeed, sponsorship of meetings like this is an essential part of Autism Speaks’ commitment to advancing innovative autism research.

The New York Academy symposium brought together respected experts working on translational autism research from the proverbial bench to the bedside. The day was filled with stimulating scientific discussion that helped those of us involved in this research to align our research priorities.

In this week’s “Science in the City” podcast from the New York Academy (click the image below to access the podcast), you can listen in as two of the symposium’s speakers offer a behind-the-scenes look at the new technologies and treatments that could redefine how we understand autism. Eric Hollander, of the Albert Einstein College of Medicine, talks about using oxytocin, a brain chemical that fosters social bonding, as a potentially treatment for aspects of autism. And Timothy Roberts, of the Children’s Hospital of Philadelphia, discusses his use of brain imaging to identify early markers of autism—such as a tell-tale delay in how a child responds to voices and other sounds.

For more information about the translational research Autism Speaks funds, please visit our Grant Search portal, where you can learn more about specific studies on technology development, biomedical interventions, and more.

We’d love your feedback. So please leave a comment and respond to our polldaddy question of the day below the podcast link. Thanks.

Click the image to hear the podcast.

Autism Speaks Participates in FasterCures “Crossing the Valley of Death” Forum

September 23, 2010 2 comments

As more and more is learned about the biology of autism, the development of novel medicines to treat its core symptoms is no longer just a hope.  Therefore Autism Speaks was pleased to be invited to participate in the 5th annual FasterCures-Esquire Leadership Forum, devoted this year to the topic of translational research, that is, how to translate knowledge gained from basic research into products that can provide real healthcare benefits for patients.

FasterCures, a Washington D.C. think tank focused on accelerating medical solutions, is based on the founding principle that saving time saves lives.  Since 2005 they have brought together a cross-disciplinary group of innovative thinkers to explore novel approaches that hold the potential to accelerate the search for new treatments and cures for diseases.  With representatives of biotechnology, pharmaceutical and patient advocacy organizations in attendance, the theme for this year’s small workshop was to determine action items to achieve innovation in drug development.   Attendees agreed that in order for this to happen as fast as possible, there needs to be better integration between all stakeholders – patients, financiers, academic researchers and for-profit companies alike.  The meeting participants called for the identification of new business models and research paradigms to achieve this integration.

Full of buzz words such as “open innovation,” “collaboration,” and “entrepreneurship,” the discussions focused on identifying the organizational and cultural barriers that influence the interface between traditional academic research and industry-related drug development.   This interface has long been called the “Valley of Death” because of the enormous difficulty in translating research discoveries into viable medical solutions.   While the government has begun several initiatives to push biomedical research forward across the Valley of Death, for-profit organizations such as pharmaceutical and biotechnology companies are beginning to unite to address the challenges that make it inefficient and, at times, impossible, to carry forward such risky and costly research on their own.  Some of the challenges identified at the meeting include the many knowledge gaps that remain in our basic understanding of human biology, the lack of financial incentives to work in some disease areas, and the constraints created by business policies that are meant to provide competitive advantages but instead often hinder progress.

The short meeting highlighted lessons learned from other industries and several new models of collaboration.   At its conclusion the participants agreed that streamlining the drug development process will involve not just procedural improvements but much more partnering than has ever been attempted before, including between individual pharmaceutical companies and between pharmaceutical companies and academia.  This opens a role for non-profit advocacy organizations such as Autism Speaks in bringing together the many diverse players, each with their own motivations and incentives.   Towards this end, Autism Speaks has recently formed a Translational Research Initiative that aims to enhance communication between academic scientists and industry representatives and nurture our renewed hopes for successful translational research in autism and new healthcare solutions.

Read more about translational research from our Chief Science Officer, Dr. Geri Dawson.

Opening the door to new medicines for ASD

May 3, 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.

On Friday, the New York Times published a story about a small clinical trial for a drug that ameliorated some of the symptoms of Fragile X Syndrome in some of the participants in the trial. Single-gene disorders, such as Fragile X Syndrome have been instructive in helping us understand the biology of the broader autism spectrum disorders (30% of people with Fragile X have an ASD). The effort described in the New York Times is not singular, but instead an area of active pursuit by many. Here is some history behind the Fragile X drug story and a summary of clinical trials for single-gene causes of ASD.

As noted in the article, the excitement began in 1991 when Steve Warren, Ph.D. (Professor at Emory University and member of Autism Speaks’ Scientific Advisory Committee) and his colleagues identified the gene, FMR1 (fragile X mental retardation 1), that causes Fragile X syndrome.  At that point, Warren and others began probing the FMR1 gene pathway to learn its properties and seek a way of correcting the genetic error. The promise of basic research findings was coming to light in Fragile X as early as 2005, with a small workshop organized by Autism Speaks’ staff titled “Promising new leads for autism research: a potential cure for Fragile X” at the International Meeting for Autism Research (IMFAR).  At this meeting, Mark Bear, Ph.D. (MIT), Tom Jongens, Ph.D (UPenn) and Bob Wong Ph.D. (SUNY Downstate) presented preliminary findings related to a theory that Fragile X may be caused by over-excitation of synapse (the connections between nerve cells).  Proper functioning of the connections between nerve cells requires a balance between excitatory and inhibitory neurotransmitters.  It appears that the FMR1 gene was causing this balance to be disrupted so that there was an abundance of the excitatory influences.   These researchers found that by damping the activity of a common excitatory neurotransmitter (glutamate) in the brain, many of the symptoms that characterized the animal models of Fragile X disorder disappeared.  This theory was referred to as the mGluR theory (for metabatropic Glutamate Receptor) of Fragile X. The drugs that produced improvements in animal models are called mGluR antagonists, because they act by blocking the actions of this glutamate receptor.

Previously, it was believed that one must act early in neurodevelopment to see any improvement in the symptoms of ASD. This basic research was incredibly exciting because several labs were learning that behaviors related to ASD could be ameliorated with drugs in adult animals.

That was several years ago and one might wonder what is taking so long to see useful medicines for these disorders. The process of approving drugs in any field is long and arduous (see blog on translational research and what Autism Speaks has funded). The translation of basic research into viable drugs in clinical trial is often referred to as crossing the “Valley of Death” as so few molecules tested in basic research make it through the process to become useful medicines. That said, several efforts have been made to create drugs for single-gene disorders related to ASD (see 2008 Top 10 story).

In 2008 researchers from the MIND Institute and Rush University reported results from the first trial of mGluR5 antagonists. Results from the small trial indicate that six out of the twelve adults with Fragile X showed improvements in cognitive deficits. This was the first promising news that mGluR drugs were safe and effective in humans and are related to those reported in the New York Times’ article from the Novartis study, which began around the same time.

Seaside Therapeutics is a small biotechnology company founded by Dr. Bear to see if the promising results observed in animals could be offered to families. In 2008, Seaside began enrollment for a clinical trial using a drug that would also dampen glutamate activity but through a different pathway for treating Fragile X.  This drug enhanced the activity of a class of receptors that typically suppress glutamate activity. Seaside Therapeutics has expanded this trial to include patients with autism, and has also launched a clinical trial of its own formulation of a specific mGluR5 antagonist for Fragile X.  If positive results are found, the next step will be to test these medications on individuals with ASD who do not have Fragile X syndrome.

We’ve been talking a lot about Fragile X, but there is another disorder, called Tuberous Sclerosis Complex (TSC), which offers another path to understanding ASD (approximately 25-50 percent of people with TSC also have an ASD). In 2008, UK researchers conducting a clinical trial with individuals with TSC reported positive outcomes on short-term memory tests of those receiving treatment. Rapamycin, the drug used in this trial and already FDA-approved for cancer, targets the brain signaling pathway that has been found to be disrupted in TSC and that has recently been implicated in autism as well (see 2007 Top 10 story related to TSC and 2008 Top 10 story about translational research).

Basic research in the biological pathways highlighted by genetic studies of Fragile X and TSC was the starting point for these exciting clinical trials. Autism Speaks continues to identify basic research opportunities that may lead to successful treatments as well as support the translation of research on molecules that have shown promise in the lab to medications that help families.

How can we develop medications that can improve the lives of persons with ASD?

April 8, 2010 11 comments

By Geri Dawson, Chief Science Officer, Autism Speaks

When I am giving talks to families about the research Autism Speaks funds, I am sometimes asked why we are funding a particular study when that study appears to have very little to do with the majority of people who actually are living and struggling with autism.  This especially comes up when I am talking about studies involving animal models, brain tissue, and rare genetic conditions.  Parents often express their frustration that scientists have not yet developed medications that can improve the quality of life for people with autism, medications that can help a child or adult with autism spectrum disorders (ASD) communicate better or be more comfortable around other people.  I realize then that the connection between many of the studies we fund and our goal of developing medications that can help people with autism may not be clear.  In this article, I hope to illustrate how many of the individual studies that we fund – which in isolation may not seem relevant –  are part of a discovery and development process ultimately aimed at providing medications that can improve the life of individuals with ASD.

I will begin with some background on the process of moving from basic laboratory studies to delivery of a useful medication to the community, a process often referred to as “translational research.” The process of drug discovery begins with identification of a “drug target.” A drug target is a component of a biochemical pathway, sometimes referred to as a “signaling” or “metabolic” pathway.  How do we figure out what signaling or metabolic pathways are affected in ASD? One way is to closely examine the actual brain cells of persons with autism, which is only possible with post-mortem brain tissue donated by families (view a recently funded study using post-mortem brain tissue).

Another way is to use animal models (see a perspective on mouse models from Craig Powell) to study the effects of a genetic mutation that is known to result in ASD or ASD symptoms. It has also been useful to start by studying conditions such as Rett syndrome and Fragile X syndrome because the genetics of these conditions are well understood.  In addition, we know that these conditions are often associated with autism (e.g., about 30 percent of individuals with Fragile X also have autism).  Animal models of these syndromes are becoming well developed, allowing scientists to study how the genetic mutation influences the biochemistry and brain functioning (view a recently funded study of synaptic alterations in the amygdala).  These types of studies pointed scientists to specific signaling pathways; for example, a pathway involving two neurotransmitters: GABA and glutamate.  These chemicals are crucial for neurons (brain cells) to establish a communication network through the formation of synapses (connections between neurons).  Specifically, the genetic mutation alters the amount of these chemicals released in the brain (i.e., too much glutamate), resulting in over-excitation of the neural circuits.  This disrupts learning.

Interestingly, at the same time these discoveries were being made, other scientists discovered that many of the genetic mutations that result in autism also disrupt the functioning of the synapse (view a recently funded study of synapse function).   The strategy here is to look for common signaling pathways that are disrupted by different risk genes.  These pathways offer the best hope for developing a medication that can be helpful not just with one genetic subtype of ASD, but more generally for many individuals who have ASD (even those where an environmental trigger might have been involved).

The process of drug target identification

Once a disrupted pathway or pathways contributing to a condition is discovered, scientists can start testing (“validating”) whether certain medications can restore the functioning of that pathway and improve behavioral functioning in animal models and humans.  Another strategy for testing different medications is to examine the effects of the medication on cells (neurons) derived from freshly isolated post-mortem brain tissue that was donated by individuals with autism through Autism Speaks’ Autism Tissue Program.

Currently, several medications that are designed to improve behavioral functioning in autism are being tested in persons with associated genetic disorders such as Rett syndrome, Tuberous Sclerosis, and Fragile X syndrome (view two recently funded human clinical trials of medications for Rett syndrome and Tuberous Sclerosis ). If these medications are found to improve behavioral functioning in individuals with these conditions, plans to study some of these medications with people with ASD will follow.  The hope is that because these conditions share some biological and behavioral similarities, these same medications will be more widely effective.  At the same time, drawing from what we have learned about the role of glutamate from studies of Fragile X syndrome, Autism Speaks is currently funding a “phase one” or “proof of concept” clinical trial of memantine, a medication that reduces the availability of glutamate, for persons with ASD.  As we understand more about the underlying biology of ASD using the strategies described above, there will be more promising leads for new medications that can improve the lives of persons with ASD.

The process from target identification to FDA approval of a new medication is arduous.  Animal and human studies are needed to examine safety, side effects, optimal dosing, and other factors (these are referred to as Phase I, II, and III clinical trials).  This “drug development pipeline” involves the collaboration among agencies such as the NIH and Autism Speaks that provide research funding; academic scientists who often conduct the high risk research that leads to target identification and validation; pharmaceutical companies who, once a target is validated, have the capability and resources of conducting the larger Phase II and III trials; and the FDA who is responsible for approving the medication for wide usage.  This collaboration is essential for drug discovery and development.

Translational research moves findings from the lab to the families.  It is one of many diverse areas of research emphasis at Autism Speaks.  This type of research provides hope for the future.  But, at the same time, we are funding studies that have more immediate impact on people lives.  These include studies of novel behavioral and other types of interventions that can be quickly implemented by parents, therapists, and teachers, as well as many others (see examples of recently funded studies on Pivotal Response Training and Cognitive Enhancement Therapy that can have immediate impact.  This balance between short- and long-term research is a key part of Autism Speaks’ overall funding strategy.

Learn more about the grants recently funded by Autism Speaks.

5|25: Celebrating Five Years of Autism Science Day 11: Translational Research Takes Hold

February 11, 2010 Leave a comment

In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 11th item, Translational Research Takes Hold , is from Autism Speaks’ Top 10 Autism Research Events of 2008.


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