NINDS Public Crowdsourcing Community Transformative Research Priorities for the Epilepsies

We propose a bold initiative to share data, infrastructure, new technologies and methods across centers to tackle some of the major challenges in treating refractory epilepsy. There is a clear gap between recent advances in technology to treat refractory seizures and their clinical translation. This is largely because individual centers do not have a sufficient number of patients or technical know-how to do the statistically... more »

Some of the greatest progress right now in precision therapies for genetic epilepsies is the result of parents of children with genetic epilepsies forming nonprofit organizations. These non-profits then raise funds for medical research. These organizations understand the urgency of the situation and they drive progress by being laser-focused on a specific genetic epilepsy. These genetic epilepsies are arguably among the... more »

This idea would accelerate promising treatments for the many stakeholders interested in advancing genetic therapies. Many of the patient advocates for monogenic epilepsies are viewing genetic therapies and a potential path towards a cure, with many working independently to achieve their goals. There have been innumerable advances in genetic diagnoses, availability of genetic testing (although there is more to do) and... more »

As a community of 19 patient and professional groups across the epilepsy community, we applaud the work of the Benchmark Committee and NINDS for launching this open call for transformative priorities for "Curing the Epilepsies". Looking back over the 20 years invested in national conferences toward Curing the Epilepsies and 3 cycles of Benchmarks to set priorities, we are concerned that progress for persons living and... more »

This idea would assist the basic research community in transforming preclinical findings to clinical application.

If more research was done, specifically on the link between epilepsy and late stage pregnancy, more OB/GYNs could be educated on the need to induce earlier to prevent epilespy.

Metabolic and biochemical pathways are an understudied research area in the epilepsies. Biochemical pathways provide crucial links between gene expression (e.g. via epigenetic modification), energy metabolism (mitochondria, ATP), neuron-glia interactions, and finally neuronal excitability. Derailment of metabolic functions can affect a complex system such as the brain on multiple different levels and metabolism or biochemistry... more »

For many genetic epilepsies the pathomechanisms are not known making rapid identification of novel drug targets challenging. Identifying genetic modifiers of high-risk epilepsy alleles using a variety of approaches (CRISPR screens, leveraging natural genetic diversity in model organisms, human modifier studies using large patient repositories) may inform key genes involved in disease mechanisms and could illuminate drug... more »

More substantive research priorities, however well framed and targeted, can not alone overcome the inefficiencies and silo-ed structure for clinical care and research in the epilepsies.

By integrating clinical care and research—the standard for decades in pediatric oncology—we will get on a path where we will start seeing improvements in the quality of life for all those living with and too often dying from epilepsy.... more »

This priority will transform epilepsy research by integrating modern science into modern care for patients with epilepsy.

For example, a patient with as yet unexplained non-acquired epilepsy should be considered to have genetic epilepsy until proven otherwise and appropriately evaluated. If the first line of evaluation is unrevealing he or she should have an iterative re-analysis of cause in tandem with empiric therapy.... more »

The AES views this as the most important research endeavor for the next 5 years. We suggest a revision to explicitly state that new models must mimic human etiologies.

 

The lowest hanging fruit for epilepsy models is to use CRISPR-knock-in (KI) strategies to create mice expressing human gene variants rather than simply presuming gene knockout or over-expression will accurately model a loss- or gain-of-function mutation.... more »

This should be a clear mandate for future and collaborative investigation in epilepsy, as it provides an opportunity to bring in scientists from disciplines outside of the epilepsy field.

The American Epilepsy Society considers this a high priority. As in human cancer, there will likely be common and overarching processes or mechanisms that lead to the establishment of the epileptic network. By analogy, all cancers stem from abnormally exuberant cell proliferation, and epilepsy reflects abnormal synchrony of neural networks. But the processes and mechanisms leading to seizures in SCN1A may be very different... more »

AES believes this is high public health priority as it will save lives i.e., to identify patients at higher risk for SUDEP and thus particularly in need of pharmaco-treatments or preventative devices (AICD) or patient surveillance. It will, however, be a major challenge due to ascertainment and low (sporadic) sample size worldwide. A genetic approach to identify genes associated with SUDEP is laudable though it seems... more »

The American Epilepsy Society views this topic as a high priority that should encompass strategy to incorporate the expertise from experts in immunology and neuroimmunology. Some revisions would help to ensure its transformative nature.

This focus should be on epilepsy alone, as the co-morbidities add a level of complexity that may make progress slow.

With genetic and epigenetic mechanisms represented strongly in other... more »