Meet the Experts: Dr. Ingrid Scheffer

 

Dr. Ingrid Scheffer

Dr. Ingrid Scheffer

When I got in touch with Dr. Ingrid Scheffer she was away at an epilepsy conference in Bologna, Italy, after having just hosted a major Dravet Syndrome conference in Melbourne. We are very grateful that the globe-trotting epilepsy expert has agreed to participate in the Denver KCNQ2 Summit. As she catches her breath back home in Australia, we will “beam” her in (if she can sit still long enough!).

Professor Scheffer is Chair of Pediatric Neurology Research at The University of Melbourne and Senior Principal Research Fellow at the Florey Institute of Neuroscience and Mental Health. She is a founding fellow of the Australian Academy of Health and Medical Sciences and is currently its Vice-President. She has served the International League Against Epilepsy in many capacities and held the Chair of the ILAE Commission for Classification and Terminology from 2009 until 2013. Read more about her background here.

Dr. Scheffer has received numerous awards for her groundbreaking work. One of her recent accolades is the prestigious 2012 L’Oréal-UNESCO Laureate for Women in Science for the Asia-Pacific Region. These annual awards are given to five women scientists, one from each of five global regions, whose exceptional careers blaze trails for the next generation of women scientists. Dr. Scheffer was the first to win for epilepsy research, and it is rare for this prize to be awarded to a physician-scientist.

 

Dr. Scheffer’s work is praised on the UNESCO website:

Ingrid Scheffer is helping to transform the diagnosis and treatment of epilepsy, a brain disorder characterized by seizures and other symptoms that can be extremely disruptive to the lives of the 50 million people affected by it. She has described several new forms of epilepsy and her research group was the first to uncover a gene for epilepsy and subsequently, many of the genes now known to be implicated. These revolutionary findings, which have already improved diagnosis and treatments for many patients and may lead to the development of new therapies, can also be used for genetic counselling. Professor Scheffer’s goal is to ‘make a major difference to patients and families through science’.

Professor Scheffer collaborated with the Belgian group of Dr. Sarah Weckhuysen and Professor Peter de Jonghe to delineate KCNQ2 encephalopathy. There had been a few previous reports of single patients with severe disorders and mutations (abnormalities) of the KCNQ2 gene but the disorder had not been well recognized.  Their team identified a group of children and delineated this severe disorder, now recognized worldwide.

Professor Scheffer has worked with the Belgian group to report a second group of patients including a more mildly affected child that she looks after, expanding our understanding of the presentations of this disease. Get a glimpse of Dr. Scheffer’s work with the daughter of our good friend Sara James Butcher, in a 30-minute documentary for the “Australian Story” series.

KCNQ2 encephalopathy is one of the severe epilepsies of infancy and childhood known as developmental epileptic encephalopathies which are now recognized to occur due to mutations in a large number of genes. Typically a child has a mutation in one gene that arises newly in the child and is not inherited from their parents. By recognizing a specific disease such as KCNQ2 encephalopathy, Dr. Scheffer explains, we can learn which medications control seizures and which medications make seizures worse. We can learn about the outcome of this disease and the various medical problems (co-morbidities) that may occur such as autism spectrum disorders, cerebral palsy, sleep and feeding disorders.

Dr. Scheffer says the biggest challenge she faces in her work is finding enough hours in the day to care for her patients and families and to fulfill her other roles of teaching and mentoring young clinicians and researchers and working on her research, let alone her administrative responsibilities in the hospital and university – and finding time to see her own wonderful family and friends. She is passionate about her patients and her research and her dream is to find a cure to these devastating disorders.

 

 

 

Meet the Experts: Dr. Edward Cooper

Edward Cooper

Dr. Edward Cooper

It was the first week of January, 2012. My nephew had received his KCNQ2 diagnosis in November, but so far we had found no particularly useful information, no foothold in the mountain we knew we would have to start climbing. All we had were 4 letters and a number.

Maybe it was pure New Year’s optimism that made me try Googling K-C-N-Q-2 all over again. It’s a time of year we believe more than ever in the power to make positive change. So it was in that spirit I found someone named Dr. Ed Cooper down in Texas. There was an email address. I sent it to my brother Mike and asked, “Why not give it a shot?”

Mike composed a note to Dr. Cooper, hit send, and prepared for a long wait for a response. But the reply came the very next day, and so began an amazing journey of collaboration, discovery, and connection. We are so grateful for Dr. Cooper and his tremendous support. And we encourage you to get to know him too! Register your child in his RIKEE project to help make positive change in the understanding of KCNQ2-realed epilepsy.

Q.Can you briefly describe your background?

A.I grew up in the northeastern US, attended Yale, studying history and pre-med, and worked as a lab tech at UC San Francisco for a couple years before returning to Yale as an MD PhD candidate.  I returned to UCSF for my neurology residency training, and stayed on as a post-doc before establishing my own lab.

Q.How did you first get interested in studying epilepsy and the KCNQ2 mutation?

A.Before KCNQ2 was discovered, I had already worked on related voltage-gated channels for about 10 years during my PhD and post-doc.  As a neurologist in training, I anticipated epilepsy would be related to channels more clearly than was then known—in fact, others had begun to uncover how mutations in channels could result in diseases, both in experimental animals and man.  My mentors at UCSF, Lily and Yuh Nung Jan, had cloned the very first potassium channel gene, showing that its mutations caused attacks of uncontrollable shaking in a widely used genetic model.  Lily was asked to peer review the first papers describing the link between KCNQ2 and KCNQ3 and human epilepsy in 1998. When the papers were accepted, Lily asked me, as the only neurologist in her research group, to help in preparation of an accompanying editorial. I was fascinated by the new work, switched my postdoctoral project to KCNQ channels, and published my first papers in collaboration with Lily in 1999-2001. That work allowed me to begin my independent lab.

Q(2).What are the biggest challenges you face in your work? What inspires or drives you as a researcher of genetic epilepsies?

A.Interestingly, I think of your two questions as inextricably linked—the challenges are inspiring.  First, I am in this to help the patient–that’s the fundamental goal. Second, I am inspired by the beauty and surprises of the brain’s mechanisms, appreciation for that is something that deepens with training. Third, the collaborative team spirit in research, learning from great teachers and working with able students, makes it fun even when it is difficult—with KCNQ2 this has now been broadened to include the collaboration with parents and families that has become so important for our work.

Meet the Experts: Dr. John Millichap

Dr. John Millichap

Dr. John Millichap

Dr. John Millichap is next up in our Meet the Experts series.

He is a Pediatric Epileptologist in the Comprehensive Epilepsy Center, Ann & Robert H. Lurie Children’s Hospital of Chicago, and Assistant Professor of Pediatrics and Neurology at Northwestern University Feinberg School of Medicine. He completed residency in pediatrics at the Brody School of Medicine at East Carolina University, residency in Child Neurology, and fellowship in Clinical Neurophysiology / Pediatric Epilepsy at Children’s Memorial Hospital (now known as Lurie Children’s) and Northwestern University Feinberg School of Medicine.

Jack is very fortunate to have Dr. Millichap caring for him as a patient, and we are privileged to have his tireless help as the medical adviser to the Jack Pribaz Foundation.

 

Q.How did you first get interested in studying epilepsy and the KCNQ2 mutation?
A. I developed my subspecialty interest in the evaluation and treatment of epilepsy during my Child Neurology training in Chicago under the mentorship of Douglas Nordli, MD, the head of the Epilepsy Center at Lurie Children’s.  After the first patient with KCNQ2 encephalopathy was diagnosed at Lurie Children’s, his parents contacted Dr Ed Cooper at Baylor School of Medicine, who has provided support and mentorship for my research in this field.

Q. What are the biggest challenges you face in your work?

A.One of the main goals of epilepsy treatment is to achieve no seizures, without side effects.  Knowing the cause of the seizures is not only important for choosing the right treatments, but also for parents’ peace of mind and to end the need for continued testing.

Q. What inspires or drives you as a researcher of genetic epilepsies?

A.Caring for treatment-resistant epilepsy is a challenge.  I am hopeful that improvements in genetic testing methods and the increase in knowledge about the causes of epilepsy will improve the lives of children with epilepsy.

 

Meet the Experts: Dr. Kristen Park

Dr. Kristen Park

Dr. Kristen Park

Dr. Kristen Park and her colleagues at Children’s Hospital of Colorado have seen a remarkable concentration of patients diagnosed with KCNQ2-related epilepsy, making Denver a perfect place to get parents and medical professionals together. The Jack Pribaz Foundation, and I’m sure the entire KCNQ2 community, is grateful to Dr. Park and the Children’s Hospital of Colorado for opening their doors and welcoming us all to the Denver Summit, which is coming up soon on September 18 and 19.

We can’t wait! To tide us over until then, we continue our Meet the Experts series with a brief introduction to the gracious Dr. Park.

Q.Can you tell us a little bit about your background?

A.I grew up in Baltimore Maryland and attended University of North Carolina for undergraduate studies – go Tarheels!  My interest in Neurology grew out of college studies in biologic Psychology.  Prior to medical school, I worked for the Epilepsy Association of Maryland and thus began my journey into this field.  I went to medical school at the Mayo Clinic, residency at Penn and the Children’s Hospital of Philadelphia (CHOP), and epilepsy fellowship at Children’s Memorial Hospital in Chicago.  I currently practice at the Children’s Hospital of Colorado where I have been for the last 6 years.

Q.How did you first get interested in studying epilepsy and the KCNQ2 mutation?

A.Epilepsy is an incredibly heterogeneous disorder with many different causes and manifestations making it interesting to study.  It also means that there is no single answer to all the problems and questions such that many minds are needed for research.  In children, genetics is playing a bigger and bigger part of our understanding of epilepsy.  I have started to work in our Neurogenetics clinic trying to diagnose children with severe and complex neurologic syndromes.  This exposed me to many new aspects of epilepsy and challenged me to understand them from a more scientific perspective.  After this, it was my patients and their families who piloted the boat.  They reached out to Ed Cooper and helped me connect with him so that as additional patients were diagnosed, he could study genetic mutations and we could pool our experiences with treatment.

Q.What are the biggest challenges you face in your work?

A.The biggest challenge for me is seeing children suffer with epilepsy and all its comorbidities without having effective means to treat all of them.  There are also insufficient resources for families in the community and the healthcare system – long wait times for appointments, limited mental health services, overburdened developmental disability services, insurance hassles, etc.

Q.What inspires or drives you as a researcher?

A.I am driven by the possibility of personalized medicine.  The potential to obtain a specific diagnosis for each patient with epilepsy and target treatment to the fundamental cause of seizures to create better outcomes and prognoses.  This is where I feel medicine is heading and it makes for exciting research.

 

Meet the Experts: Dr. Sarah Weckhuysen

For those who will be traveling to the Denver Summit in September, and also (or maybe especially) for those who will be with us in spirit, we wanted to introduce you to some of the experts who will be sharing their insights on KCNQ2-related epilepsy.

Dr. Sarah WEckhuysen

Dr. Sarah Weckhuysen

We begin this series with Dr. Sarah Weckhuysen, who was the first author on the first paper to describe KCNQ2 encephalopathy and who will be traveling the farthest to be with us!

Q:

Can you describe your background for us?

 

A:

I am a neurologist/epileptologist, born and raised in little Belgium in Europe. After obtaining my Neurology degree, I worked for some years as an epileptologist in the tertiary epilepsy center Kempenhaeghe in the Netherlands. This work with often treatment resistant epilepsy patients fuelled my fascination for the underlying causes of (severe) epilepsies. In the last few years I therefore intensified my research activities at the Neurogenetics group of the University of Antwerp in Belgium, and obtained a PhD on the topic of genetics of epileptic encephalopathies. My research interests are focused on the delineation of epileptic syndromes, and the genetics of (early onset) epilepsies and febrile seizures. I’m also an active member and coordinator for the European consortium EuroEPINOMICS-RES, which focuses on the genetics of rare epilepsy syndromes.

Q:

How did you first get interested in studying epilepsy and the KCNQ2 mutation?

 

A:In the Neurogenetics group we have been screening the gene KCNQ2 for several years in patients with the mild familial epilepsy syndrome “Benign Familial Neonatal Seizures.” In 2004 we discovered that de novo mutations in this gene (mutations only present in the patient, not in the parents) could also be found in patients with benign neonatal seizures without a family history of epilepsy. Since then we offered this genetic test to patients with neonatal seizures coming from around Europe. One of these patients in which we confirmed a de novo KCNQ2 mutation, subsequently appeared to have a more severe disease course than expected, and her development clearly appeared to be slower than normal. We wondered whether this was related to the KCNQ2 mutation or a pure coincidence, and we decided to further investigate this question. In collaboration with Ingrid Scheffer’s group from Australia, we collected a large group of children with neonatal seizures and subsequent developmental delay, and searched for KCNQ2 mutations in this group. We indeed found a de novo KCNQ2 mutation in 10% of these children. That’s how the disease entity KCNQ2 encephalopathy was first described.

Q: What are the biggest challenges you face in your work?

 

A: One of the biggest challenges for me, and I believe for all people working in epilepsy genetics now, is how to take our research one step further: During recent years our possibilities to identify new genetic causes for epilepsy have increased tremendously due to technological advances. More and more children with childhood epilepsy are offered a genetic diagnosis. We now have to think how we can translate this genetic knowledge into better patient treatment. Because at the end as a clinician, I not only want to provide a diagnosis to a patient, but also a cure.

Q:What inspires or drives you as a researcher of genetic epilepsies?

 

A:This strongly relates to the previous question. For me studying the genetic causes of epilepsy is a way towards a better understanding of the underlying causes and mechanisms in epilepsy. This is an important issue, as one third of the patients with epilepsy have treatment-resistant seizures, and thus do not respond well to currently available anti-epileptic drugs. Understanding what causes seizures in specific groups of patients is a starting point for the development of new and more specific treatment options for these patients. Although at this moment a genetic diagnosis rarely influences treatment choices in epilepsy, I do believe this is something we should aim for in the future.