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Can Translational Neuroscience Deliver Effective Treatments for Autism?

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IMFAR keynote speaker identifies barriers to delivering better treatments and how international collaboration can break the logjam

IMFAR keynote speaker identifies barriers to delivering better treatments and how international collaboration can break the logjam

May 15, 2014

Neurodevelopmental psychiatrist Declan Murphy, of King’s College London, delivered the first keynote address of the 2014 International Meeting for Autism Research (IMFAR) today in Atlanta.

Dr. Murphy began by asking two questions: Why are there so few effective treatments for autism? Can translational neuroscience help deliver such treatments? With these two questions, he went on to describe:

* Current barriers to the delivery of more-effective treatments;

* What the research community can deliver to the autism community in the short term despite such barriers; and finally

* The steps needed to overcome current barriers to achieve truly breakthrough treatments.
 

Follow all of Autism Sneaks’ daily coverage of IMFAR 2014 here.

Current barriers
With dark humor, Dr. Murphy noted that, in preparing for his lecture, he’d spent months identifying all the large clinical trials of pharmacological treatments for autism’s core symptoms. He then showed a blank slide to illustrate the dearth.

At this point, he said, all attempts to develop broadly effective treatments will be plagued by the fact that we can’t yet identify the underlying cause of the disorder in the vast majority of those affected by it. Without such information, there’s no way to predict which individual are most likely to respond to which promising new medicine, he explained.

Even current behavioral treatments are limited by this inability to identify autism subtypes, Dr. Murphy added. “I think there’s good evidence that some behavioral and educational treatments are very effective,” he said. “But we don’t know who will respond to them.”

Better serving those with autism now
Nonetheless, Dr. Murphy argued that there’s much that can be done to improve the health and quality of life of those with autism. This begins, he said, with improved and consistent guidelines for treating autism’s many associated conditions. In particular, he called out the need to better address high rates of anxiety, depression, sleep disorders, seizures and attention deficit problems in children and adults with autism.

“In particular, we need to be much better at addressing these needs across the lifespan,” he emphasized. (Learn more about how Autism Speaks is addressing these issues through its Autism Treatment Networkhere.)

Engaging individuals affected by autism
Dr. Murphy also urged scientists in the audience to confer more closely with those affected by autism. “Consider, for example, those individuals who have developed their restricted interests in important ways. It’s important to remember that they may not want to lose those interests or their related abilities.”

In developing new treatments, he said, researchers need to learn what individuals with autism want. What symptoms cause them the most problems? In what kinds of clinical trials would they participate?

“We need willing participants in our clinical studies, and we need lots of them,” he said.

The need for objective biomarkers
Dr. Murphy also highlighted the need for more objective measures of what constitutes a successful outcome from a given treatment. It’s not enough to have subjective measures such as “feeling better.” A clinical trial of a cardiac or cancer drug would use very specific types of blood tests or medical imaging to gauge results, he said by way of example. The field of autism needs brain-based biomarkers.

Many genes, fewer pathways?
Hundreds of genes – and the brain processes they control – have been implicated in autism. But with few exceptions, no one gene can account for more than 1 percent or so of all autism cases.

This might suggest an overwhelming challenge in the search for individualized treatments. Fortunately, research continues to show that these many genes affect a far smaller number of shared brain pathways, Dr. Murphy said. He called for more research to better identify these common pathways. These can then become the targets for future treatments.

In particular, he highlighted research on imbalances in excitatory and inhibitory neurotransmitters. These are brain chemicals that stimulate or calm brain activity.

International collaboration the answer

A huge amount of research is needed to identify autism subtypes and determine which promising medicines or other treatments can best provide individualized treatment, Dr. Murphy said. This, in turn, requires international collaboration.

A historic collaboration with Autism Speaks
In Europe, this is being done through the unprecedented public-private partnership known as the European Union Innovative Medicines Initiative. The autism-specific branch of this initiative is EU-AIMS. In describing its important work, Dr. Murphy paused to thank Autism Speaks – which is playing a unique consulting role in the endeavor.

“I’d like to take this opportunity to express a public thank you to Autism Speaks for helping us develop the vital resource of a biobank,” Dr. Murphy said. As he thanked Autism Speaks, Dr. Murphy projected an overhead slide showing that many Autism Speaks resources that are fostering the work of EU-AIMS scientists. These included the Autism Speaks Autism Treatment Network, Autism Genetic Resource Exchange, the Autism Tissue Program (now part of Autism BrainNet) and the Autism Genome Project.

Finally, Dr. Murphy called for greater international collaboration to deliver on the promise of effective autism treatments. The global research community must better coordinate the many small and disparate trials being conducted around the world, he said. Autism researchers must better understand how the different measures they use relate to one another. “How does my eye tracking data map onto your cellular data?” he asked by way of example.

After the keynote address, Autism Speaks Chief Science Officer Rob Ring expressed appreciation for Dr. Murphy’s breakdown of the challenges and opportunities for medicines development in autism. "His presentation highlighted the critical role that pre-competitive research consortia like EU-AIMS will play in accelerating the pace and improving the focus of the research needed to deliver new treatment options for individuals with ASD," Dr. Ring said.

Dan Smith, Autism Speaks senior director for discovery neuroscience added: “EU-AIMS emphasizes using basic and clinical research to ensure we apply the cutting-edge of what we know from all areas. This is what will drive us toward better, personalized medicine.”

Read more about Autism Speaks and EU-AIMS here.

 


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