ILAE/AES Translational Research Task Force
ILAE/AES Joint Translational Task Force
Current leadership (2017-2021):
AES co-chairs: Aristea Galanopoulou and Greg Worrell
ILAE co-chairs: Terry O’Brien (Australia) and Matthew Walker (UK)
AES members: Rick Staba, Anne Anderson, Manisha Patel, Kevin Kelly
ILAE members: Gunther Sperk (Austria), Rudiger Koehling (Germany), Heidrun Potschka (Germany), Steven Petrou (Australia)
In September 2012, an international group of epilepsy investigators and representatives from funding agencies and patient advocate organizations participated in London, UK in the first Joint International League Against Epilepsy (ILAE) – American Epilepsy Society (AES) Translational Workshop. Their goal was to create a roadmap to optimize preclinical translational epilepsy research and lead to new transformative treatments for people with epilepsies, including anti-epileptogenic, drug-resistant, and anti-comorbidity therapies (Epilepsia, 2013, Vol 54, s4). A task force was formed to advance the following initiatives.
ILAE/AES Joint Translational Task Force (2013-17): During this first cycle, the co-chairs of this task force (Jacqueline French, Aristea Galanopoulou, Terence O’Brien, and Michele Simonato) along with the elected members (Amy Brooks-Kayal, Marco de Curtis, Akio Ikeda, Frances Jensen, Solomon (Nico) Moshé, Asla Pitkanen, and Helen Scharfman) formed working groups to address the following tasks:
TASK1: The first initiative will generate an infrastructure to harmonize and optimize preclinical electrophysiological studies so that data gathered from numerous experiments across multiple labs can be more effectively used to design clinical studies and predict effects in humans. The co-leaders (Aristea Galanopoulou, Marco de Curtis, and Akio Ikeda) and their selected working groups aimed to (a) develop standards for recordings and interpretation of electrophysiological studies conducted in live animals or using in vitro seizure models, (b) evaluate their relevance to human studies, (c) optimize the use of video-EEG depositories and analysis software to harmonize epilepsy research, and (d) disseminate these recommendations through publications and reference textbooks. The first proceedings on harmonization of methodology and interpretation of preclinical electrophysiological studies in experimental controls were published in 2017 (Epilepsia (2017), vol 58, Suppl 4).
TASK2: The second initiative will organize and coordinate systematic reviews of available preclinical data to critically evaluate how these studies predict both treatment response and biomarker development for specific clinical syndromes and comorbidities. The co-leaders (Michele Simonato, Amy Brooks-Kayal, Frances Jensen) and their selected working groups are identifying and developing approaches to generate and periodically update databases and reviews to facilitate meta-analyses of preclinical data. Systematic reviews could pave the way for large, multicenter studies and provide material for common data elements that, in turn, will simplify future systematic reviews and harmonized analyses. The first systematic review of the TASK 2 group is underway in collaboration with CAMARADES (http://www.dcn.ed.ac.uk/camarades/), with the rationale and protocol published in 2017 (Epilepsia (2017), vol 58, Suppl 4).
TASK3: The third initiative will develop common data elements (CDEs) for preclinical epilepsy research. CDEs standardize the collection of investigational data and facilitate comparison of results across studies. Based on the experience with the clinical CDEs for epilepsy, spearheaded by National Institute of Neurological Disorders and Stroke (NINDS), preclinical epilepsy CDEs are expected to ensure that important data elements (e.g., experimental conditions, EEG or behavioral data) are obtained in a similar fashion in all translational preclinical studies. The CDEs are designed to serve the needs of individual laboratories as well as research consortia. The co-leaders of this step are Jackie French, Asla Pitkanen, and Helen Scharfman, with Vicky Whittemore serving as liaison to NINDS and Aristea Galanopoulou as liaison to the TASK 1 group. As of April 2018, the proceedings of this group are in the final stages for publication at Epilepsia Open. Feedback from the scientific community is welcomed to further optimize these resources.
TASK4: The final initiative aimed to develop infrastructure for multicenter preclinical studies. These studies will represent a “Phase II” of preclinical translational studies, analogous to clinical Phase II/III multicenter, randomized, double-blinded studies, as a follow-up to “Phase I” exploratory findings generated by single laboratories. Utilizing the combined expertise and progress made through the task force, the first antiepileptogenesis study (EpiBios4Rx) has been organized by several members of the task force and funded by the NIH as a Center without Walls to tackle the needs of patients with post-traumatic epilepsy following traumatic brain injury. Preclinical results from coordinated multicenter studies may encourage industry and government to invest in a prospective therapy’s clinical development. Partnerships among government-related funding organizations (NIH, European Community), industry, philanthropic foundations and academia are essential to such initiatives. The co-leaders of TASK4, included Terry O’Brien, Nico Moshé, and Akio Ikeda.
ILAE/AES Joint Translational Task Force (2017-21): During the current cycle, the co-chairs (Drs. Galanopoulou, O’Brien, Walker, and Worrell) and the elected members (Drs. Anderson, Kelly, Koehling, Patel, Petrou, Potschka, Sperk, and Staba) of the task force agreed to continue towards the goals listed below. Working groups will be formed to engage volunteer experts in completing these tasks.
TASK1: Continue the work of the TASK1 group on:
- Creating a working classification of seizures and epilepsies in preclinical studies. This will include:
- Classification and interpretation of abnormal and epileptic EEG patterns and behavioral seizures in rodents.
- Working classification of rodent seizures and epilepsies in a manner that could translate to human seizures and epilepsies.
- Creation of a public access online Atlas of Rodent EEGs.
TASK2: Continue the work of the TASK2 group and complete the systematic review of the preclinical epilepsy studies on outcome measures.
TASK3: Continue and expand the work of the TASK3 group by finalizing and expanding the preclinical epilepsy CDEs and creating tools and avenues to facilitate their use by investigators.
By Aristea Galanopoulou
Reports of the ILAE/AES Joint Translational Task Force are summarized here.