Families Needed to Make Autism Genome Research ‘Patient-centric’

Phelan-McDermid Syndrome Foundation has pioneered how families and researchers can collaborate to advance personalized treatment of autism

Phelan-McDermid Syndrome Foundation has pioneered how families and researchers can collaborate to advance personalized treatment 

Guest post by Geraldine Bliss (left with son), chair of the Phelan-McDermid Syndrome Foundation’s Research Support Committee, and Megan O’Boyle (right with daughter), principle investigator of the foundation’s Data Network.

Phelan-McDermid syndrome – also known as 22q13 deletion syndrome – is among a handful of purely genetic causes of autism. At this year’s IMFAR, Dr. O’Boyle will co-chair a special interest group titled “Creating Patient-centric Information Commons for Autism Research.” In part, the session will focus on how large research databases such as Autism Speaks MSSNG project can help identify distinct subgroups of people with autism and, in doing so, allow them to connect with each other and advocate for tailored treatments.

News update: Today at IMFAR, researchers announced plans to use oxytocin nasal spray in a clinical trial enrolling children with Phelan-McDermid syndrome. The announcement came as part of a presentation describing how the investigators used oxytocin to reduce autism-like symptoms in an animal model of this genetic syndrome.

One of the most exciting things at IMFAR is hearing about the remarkable progress in understanding autism’s underlying biology.

Scientists have identified more than200 genetic changes as strongly associated with an increased risk of having autism. It turns out that many of these mutations cause changes in only a few of the brain’s molecular pathways. This may explain why so many different genetic conditions result in the same classic autistic characteristics.

This type of genetics-first approach to understanding autism is advancing our understanding of the brain pathways, circuits and brain structures involved in learning, memory and behavior.

Families play a crucial role
While genetic research is critical, understanding the molecular mechanisms of autism is just half of the story. To develop new treatments that improve quality of life, we need information from families – and lots of it.

Both the White House’s Precision Medicine Initiative and the House Energy & Commerce Committee’s bipartisan 21st Century Cures Act champion a precision medicine approach.

In this approach, researchers tailor new medicines to groups of patients on the basis of the specific biology or genetics underlying their condition.

Predicting whether the medicines will work or measuring how the drugs are working takes information from patients. This includes medical records, genetic data, lifestyle data, data from devices and sensors and patients’ personal perspectives.

Patient registries advance discoveries
We at the Phelan-McDermid Syndrome Foundation are so confident in this approach that we have invested the largest part of our research budget in initiatives to collect patient data. This includes our new Developmental Synaptopathies Consortium and the Phelan-McDermid Syndrome International Registry.

Just four years ago, we came to IMFAR to announce that we had just launched our web-based patient registry. Through it, families affected by Phelan-McDermid Syndrome (PMS) upload their genetic reports and other health records and answer questions about their children’s experiences. For example, the registry includes questions about seizures and sleep issues.

We are excited to return to IMFAR this year to share our recent accomplishments and lessons learned.

Our presentations at IMFAR 2014 highlight the value of parent-reported data. They are rich in the kind of knowledge that only family members and caregivers can provide. This includes information that may never make it into a patient’s medical chart but nonetheless may prove crucial to unlocking the clues to a treatment.

This data is helping us better understand PMS and how it affects people over the course of their lives. For example, we’ve learned that adults with PMS have regressive periods.

Our researchers also use the data to advance understanding of how the genetic mutations involved in PMS relate to autism and related symptoms such as speech and language impairments and epilepsy.

We’ve also learned that congenital heart and kidney problems frequently associated with PMS tend to occur in individuals with large genetic deletions. This implicates other, nearby genes in these co-morbidities.

Finally, we use the information we are collecting to help families find the clinical research studies and clinical trials that may be best suited for them.

One of the reasons our registry has been so successful is because our community has been so enthusiastically involved. More than 63 percent of those diagnosed with PMS around the world are currently participating in our registry.

Our research isn’t for just the next generation. Participating families are benefitting now. For instance, they can see how their experiences compare to those of other PMS families. They don’t have to wait for research to be funded and for publications to be written, peer-reviewed and published in scientific journals.

From isolation to family reunion
If you’ve never met another family affected by the same genetic condition … if your doctors have never cared for a patient with the same genetic condition … you feel alone in the world. By contrast, when you can click on a question about “not feeling pain appropriately” and see that 83 percent of the other patients with your condition answered “yes,” you move from feeling isolated to feeling like you’ve arrived at a family reunion!

Through an award from the Patient-Centered Outcomes Research Institute, we are now integrating patients’ electronic health records with our registry data. Our goal is to create a multi-layered resource for understanding Phelan-McDermid syndrome.

With the availability of seizure-tracking apps, wearable devices, therapeutic video games, etc., we hope to integrate even more types of data in the future.

Now is the time to harness the technology to inform research and develop treatments. We can ALL contribute, even without leaving home!

We encourage parents of children affected by PMS to participate in our registry.

If your child hasn’t been diagnosed with a genetic condition, we encourage you to participate in Interactive Autism Network (IAN).

In the near future, Autism Speaks MSSNG project promises to unite even more autism families around the common genetic signatures being discovered through whole genome sequencing. You can learn more about it here.

Finally, we encourage you to talk with your child’s doctor about chromosomal microarray or whole exome sequencing if your child has not already had these tests performed.

Recommendations from the American Academy of Pediatrics and the American College of Medical Genetics calls on doctors to consider chromosomal microarray in the diagnostic evaluation of patients with autism spectrum disorder. Chromosomal microarray detects copy number variations in addition to chromosomal deletions and duplications.

Whole exome sequencing, when used as part of an autism evaluation, detects relevant “spelling errors” in genes around 25 percent of the time.

Health insurance plans, including Medicaid, frequently cover the cost of these tests. But other times, it’s yet another battle we have to fight.  Working with a good genetics clinic can help.

In closing, we send our best wishes to the Autism Speaks community, of which we are a proud part.

Editor’s note: In related IMFAR research news, an international team of scientists reported early success using oxytocin to reducing autism-like social-avoidance symptoms in genetically engineered rat models of Phelan-McDermid syndrome. Read their IMFAR report here.

Autism Speaks is a major sponsor of IMFAR. For more daily news coverage from the conference, click here.


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