Report on First Scientific SCN8A Conference
Hosted by Wishes for Elliott
April, 2015
It is humbling to attempt to provide a summary of the first conference of clinicians and researchers working on SCN8A. When we at Wishes for Elliott decided we had to “do something” about how little was known about SCN8A once Elliott got his test results, Dr. Vanderver recommended convening such a conference. But she made it clear the real value would be if the conference was designed as a truly scientific conference, establishing of consensus on baseline knowledge, gaps in work underway, and new future directions of work.
So, much of the discussion was largely above our basic understanding but we will try and share what for us seemed like highlights and notable outcomes.
Original Objectives
Our objective was to bring together the few experts working on various SCN8A efforts across the globe into a single room to try and foster collaboration and accelerate the pace of progress on improving the understanding of SCN8A and treatments for our children. The focus would be on encouraging participants to achieve consensus on what is known and identify gaps in knowledge as well as key opportunities for promising new lines of inquiry to bring faster answers to families.
Dense and Ambitious Agenda
The core of the conference was two panels – one focusing on the state of knowledge from a clinical perspective and the second focusing on what has been learned through different approaches to “bench” research. Anyone who is at all familiar with the limited but impressive literature on SCN8A knows the deck was stacked for success as nearly all the leading practitioners and researchers were at the table.
Speakers and Topics:
(Follow links to view presentations)
Clinical Research Efforts – Moderator Ingrid Scheffer, MD
Ingrid Scheffer – Overview of the Phenotypic Picture of SCN8A
Michael Hammer – SCN8A Bio-registry efforts
Vicky Whittemore – Focus on Patient Reported Outcomes
Jack Parent – Gaps in Bio-registry, Bio-banking and Clinical Outcomes in SCN8A to Be “Trial Ready”
Barbara Kroner – Update on the Development and Opportunities of the Rare Epilepsy Network
Bench Research Efforts – Moderator Miriam Meisler, PhD
Miriam Meisler – SCN8A Mutations and Comparison with SCN1A (Dravet)
Manoj Patel – Electrophysiology of SCN8A Mutant Channels
Al Goldin – Channel Properties of SCN8A
Jack Parent – iPSc Derived Neuron Models of SCN1A and SCN8A Epilepsies
Karen Wilcox – Strategies to Screen for SCN8A Effective Drugs
Gabi Kicked Off the Conference with a Tale of their Journey
She began by sharing the many beautiful Faces of SCN8A
She also shared many facts about the profound challenges these children confront every day. The data came from a quick survey of SCN8A families on a private Facebook group and put new and important data on the table.
100% have been through a constant cycle of anti-seizure medications, many of which either fail to help or actually worsen seizures
80% have very limited motor skills with the other 20% all delayed but improving
80% are non-verbal
60% have either little or only some control of seizures
50% are dependent on a feeding tube for their nutrition
40% experience pulmonary (breathing) problems
30% have scoliosis
25% have visual impairment or cortical blindness
Our small survey may have some very significant impact on treatment of SCN8A cases. There was alarm at the results which showed that 14 out of 14 children who were on one anti-epileptic drug (Keppra or Levetiracetam) had a negative effect. If confirmed, this is the kind of information that can drastically alter standard protocols as this is often a standard first drug prescribed for seizures.
Important Information Emerged About the Complexity of SCN8A
The depth and richness of the presentations and discussion put a range of powerful facts about SCN8A on the table –making clear how complex the search for answers is certain to be. Here are a few of the major points raised:
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One gene is associated with many syndromes. And each syndrome has many related genes.
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SCN8A is consistently emerging as approximately 1% of all epilepsies. With 200,000 diagnosed annually, there could be MANY more cases, very soon.
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Location of mutation on a gene, suspected to be a differentiating factor, is not determinative of outcomes. For SCN8A, there are already known cases of children with the mutation at the same location but with opposite outcomes (severe vs. slight) and very different responses to the same medications.
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It is believed that broader genetic background is important in determining outcomes, and yet experiments with mice with an SCN8A mutation who have the same genetic background have produced different outcomes.
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There are multiple models for evaluating the nature/function of the mutation and the impact of different variables. They include iPSC Stem cells, whole cell clamp method – a DNA clone, and animal models (zebrafish, mice, etc.). There are advantages and disadvantages of each and significant cost ranges. Yet they have not yet been fully evaluated for their reliability in accurately representing results for SCN8A or for humans.
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Accurate natural histories (detailed data on condition, treatments and responses) is generally understood as a critical step for being able to move to clinical trials.
Many Outcomes – The Curve of SCN8A Knowledge Has Shifted
The pace and breadth of the meeting accelerating collaboration and expanded focus of SCN8A research has been overwhelming. Here’s some of what participants have already said:
"It was a unique day for SCN8A research and I do not doubt that you have catalyzed a redoubled effort on the part of all who were in attendance."
"I learned an incredible amount."
"I am truly honored to have been a part of this and I look forward to future collaboration."
"Fabulous meeting – let us at NIH know how we can help this fantastic effort to find answers for all of those individuals with mutations in SCN8A!"
"What a fantastic gathering…. I think we all look forward to continued and new collaborations to move this science forward."
"I have already been talking to other rare disease groups about what you accomplished for SCN8A."
"The conference was exceptional in providing an opportunity to meet the parents and caregivers (which was inspiring) and to interact with investigators using different approaches to improve the understanding and treatment of SCN8A epilepsy. I learned a great deal and made connections to move my research forward."
"Let’s stay connected by creating a list serve for SCN8A."
"We should reconvene in 18 months from now (with routine annual meetings thereafter)."
© Michael Halpern
First Conference of SCN8A Researchers and Clinicians
