Orphanet J Rare Dis. 2025 Aug 19;20(1):444. doi: 10.1186/s13023-025-03672-w.
Despite significant scientific progress since the 2012 discovery that variants in the SCN8A gene can cause human epilepsy, disease mechanisms and best practices for management of SCN8A-related disorders (SCN8A-RD) remain incompletely understood. To accelerate the rate of progress, the International SCN8A Alliance sponsored a conference in Boston, Massachusetts, on August 16-18, 2024. The goals were to identify core knowledge gaps and research priorities, and to establish a collaborative research strategy to improve quality of life. In addition to a number of family leaders representing caregiver priorities, the meeting included laboratory scientists, clinicians, and representatives from the biopharmaceutical industry.
The scientific literature and requests for proposals from epilepsy funding agencies were reviewed prior to the meeting. Stakeholder-specific surveys were conducted focusing on knowledge gaps, research priorities, and scientific roadblocks. Interviews with biotechnology leaders were conducted to identify their priorities. These data were analyzed to assess responsiveness to caregiver concerns and to identify top research priorities for advancing the field. The Caregiver survey (n = 175) revealed top challenges and identified novel therapeutics and management of non-seizure phenotypes/comorbidities as top priorities. Clinician (n = 46) and scientist (n = 23) surveys identified a number of common research priorities, partially overlapping with caregiver concerns. Five core areas emerged from integrated analysis of all four stakeholder surveys and became the focus areas of five Working Groups: (1) Transformative Therapeutics, (2) Non-Seizure Outcomes, (3) Current Therapeutics, (4) Biomarkers, and (5) Whole Brain/Whole Body.
Taking account of the concerns and priorities of the caregiver community, the five working groups identified research directions to address knowledge gaps that include both short- and long-term priorities to improve understanding of disease mechanisms and management for the spectrum of SCN8A-RD phenotypes. Challenges included identification of suitable funding mechanisms and the lack of expertise in certain methodologies and research areas. This Research Roadmap is expected to accelerate progress toward the goals of improved quality of life and transformative care for all those with SCN8A-RD.
尽管自2012年发现SCN8A基因变异可导致人类癫痫以来取得了重大科学进展，但SCN8A相关疾病（SCN8A-RD）的发病机制和最佳管理方法仍未完全明确。为加快研究进展速度，国际SCN8A联盟于2024年8月16日至18日在马萨诸塞州波士顿主办了一次会议。会议目标是确定核心知识空白和研究重点，并制定一项合作研究战略以改善生活质量。除了一些代表照顾者优先事项的家庭负责人外，会议还包括实验室科学家、临床医生以及生物制药行业代表。
会议前对癫痫资助机构的科学文献和提案请求进行了审查。针对知识空白、研究重点和科学障碍开展了针对特定利益相关者的调查。对生物技术领域领导者进行了访谈以确定他们的优先事项。对这些数据进行分析，以评估对照顾者关注问题的回应情况，并确定推动该领域发展的首要研究重点。照顾者调查（n = 175）揭示了主要挑战，并将新型疗法以及非癫痫发作表型/合并症的管理确定为首要优先事项。临床医生调查（n = 46）和科学家调查（n = 23）确定了一些共同的研究重点，部分与照顾者关注的问题重叠。对所有四项利益相关者调查的综合分析产生了五个核心领域，并成为五个工作组的重点领域：（1）变革性疗法，（2）非癫痫发作结果，（3）现有疗法，（4）生物标志物，以及（5）全脑/全身。
考虑到照顾者群体的关注和优先事项，五个工作组确定了研究方向，以解决知识空白，其中包括短期和长期重点，以增进对SCN8A-RD表型谱疾病机制和管理的理解。挑战包括确定合适的资助机制以及某些方法和研究领域缺乏专业知识。预计本研究路线图将加快实现改善所有SCN8A-RD患者生活质量和变革性护理目标的进展。
