Rationale:
Despite significant scientific advancements since SCN8A was identified as an epilepsy-associated gene in 2012, many research and clinical challenges remain. To accelerate progress with a focus on caregiver-centered priorities, the International SCN8A Alliance (Alliance) planned and hosted a Global SCN8A Research Roadmap (8ARR) in August in Boston MA.Methods:
The Alliance, along with SCN8A Global Leaders Alliance partners, brought together key stakeholders– caregivers, clinicians, researchers, and industry representatives– to develop the first 8ARR. Extensive reviews of the literature and requests for proposals from epilepsy funding agencies were performed. Stakeholder-specific surveys were crafted focusing on research priorities, scientific roadblocks, current gaps in research and clinical care. Interviews with pharmaceutical leaders were also conducted to identify similar priorities from the biotech perspective. These data were analyzed to identify common gaps and priorities. Leaders with expertise in the five initial areas were identified and asked to lead working focus groups at the workshop.
Results:
Caregivers (n=175) had wide agreement on a range of research priorities including disease-modifying treatments and gene therapies, optimizing current therapeutics, and improvements in management of extensive comorbidities. Figure 1 displays top five challenges impacting patients, many of which present opportunities for collaborative research. Table 1 gives examples of areas of agreement among stakeholders and extent of responsiveness of Clinicians (n=46) and Scientists (n=23) to Caregiver priorities. Integration across stakeholder surveys yielded five main core knowledge gap areas that became the focus of working groups at the meeting:
- Advancing Transformative Therapies
- Understanding Non-Seizure Outcomes
- Improving Current Therapeutics
- Identifying Biomarkers
- Understanding Whole Brain/Whole Body
Cross disease comparisions (e.g., SCN2A) was suggested as a sixth area at the meeting. Working groups developed research strategies to address knowledge gaps and explored opportunities for research collaborations. Both short- and long-term priorities were elaborated for the full spectrum of SCN8A phenotypes. The groundwork for implementation was laid and a plan for continued collaboration both within and between working groups was established, including coordination of next steps, identification of funding mechanisms, and specification of larger scale research projects.
Conclusions:
The meeting witnessed the coming together of the global SCN8A community to identify critical knowledge gaps and research priorities. Implementation of a Research Roadmap prioritizing these areas over the next 5 years will accelerate progress toward the goals of improved quality of life, transformative care, and eventual ending of suffering for all those with SCN8A-related disorders. Efforts are underway to establish a Global SCN8A Scientific Advisory Board with representatives from all stakeholder groups. Regular updates to the roadmap will ensure it remains responsive to the evolving landscape of SCN8A research and of patient needs and priorities.
Funding: International SCN8A Alliance