Rushing Gabrielle V, Sills Jennifer
CSNK2A1 Foundation, 1929 Van Ness Avenue, San Francisco, CA 94109, USA.
CSNK2A1 Foundation, San Francisco, CA, USA.
Ther Adv Rare Dis. 2024 Jul 25;5:26330040241249763. doi: 10.1177/26330040241249763. eCollection 2024 Jan-Dec.
Okur-Chung neurodevelopmental syndrome (OCNDS) is an ultra-rare disorder caused by variants in the gene. encodes for the alpha subunit of casein kinase 2 (CK2), a serine/threonine kinase critical in neural development. CK2 is implicated in many human pathologies, including viral infections, cancer, inflammation, cardiovascular, neurodegenerative, and psychiatric diseases. However, the mechanism of action for the variants observed in OCNDS is not fully understood, although studies suggest a loss of function or altered substrate specificity. There are no approved treatments for OCNDS, and current treatments focus on symptom management. The CSNK2A1 Foundation was established in 2018 and aims to find a cure for OCNDS and provide support to affected individuals. OCNDS presents with symptoms at varying severity, including developmental delay/intellectual disabilities, autism, disrupted sleep, speech delays/inability to speak, short stature, and, in ~25% of cases, epilepsy. The foundation has developed a research toolbox that is readily available to researchers worldwide and has awarded ~$1 million in grant funding. These efforts have provided valuable insights into CK2 biology and the natural history of OCNDS. However, additional efforts are needed to fully characterize the disease mechanism and investigate potential treatment interventions. Continued investigation into CK2 and its role in neural development holds promise for a better understanding of OCNDS and related disorders in the future. To accelerate research, we have developed a research roadmap highlighting key focus areas of landscape analysis/toolbox expansion, biomarker development, and therapeutic testing through a series of steps that are nonlinear; we expect these efforts to guide decision-making for therapeutic exploration whether that be drug repurposing, gene therapy, novel drug discovery, or a combination. In this perspective article, we describe OCNDS and the gene, highlight gaps in OCNDS research, discuss the research roadmap, and offer the founder's perspective on our growth and future opportunities.
奥库尔-钟神经发育综合征（OCNDS）是一种由该基因变异引起的极其罕见的疾病。该基因编码酪蛋白激酶2（CK2）的α亚基，CK2是一种在神经发育中起关键作用的丝氨酸/苏氨酸激酶。CK2与许多人类疾病有关，包括病毒感染、癌症、炎症、心血管疾病、神经退行性疾病和精神疾病。然而，尽管研究表明OCNDS中观察到的该基因变异的作用机制是功能丧失或底物特异性改变，但尚未完全了解。目前尚无针对OCNDS的获批治疗方法，当前治疗主要集中在症状管理上。CSNK2A1基金会于2018年成立，旨在找到治愈OCNDS的方法并为受影响个体提供支持。OCNDS的症状严重程度各异，包括发育迟缓/智力残疾、自闭症、睡眠紊乱、语言发育迟缓/无法说话、身材矮小，约25%的病例会出现癫痫。该基金会开发了一个研究工具箱，供全球研究人员随时使用，并已授予约100万美元的资助资金。这些努力为CK2生物学和OCNDS的自然史提供了有价值的见解。然而，需要进一步努力以全面描述疾病机制并研究潜在的治疗干预措施。对CK2及其在神经发育中的作用的持续研究有望在未来更好地理解OCNDS及相关疾病。为了加速研究，我们制定了一份研究路线图，通过一系列非线性步骤突出了景观分析/工具箱扩展、生物标志物开发和治疗测试的关键重点领域；我们期望这些努力能指导治疗探索的决策，无论是药物重新利用、基因治疗、新药发现还是联合使用。在这篇观点文章中，我们描述了OCNDS和该基因，强调了OCNDS研究中的差距，讨论了研究路线图，并提供了创始人对我们的发展和未来机会的看法。
