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Review
. 2024 Jul 25:5:26330040241249763.
doi: 10.1177/26330040241249763. eCollection 2024 Jan-Dec.

Patient organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome

Gabrielle V Rushing  1 , Jennifer Sills  2
Affiliations
Review

Patient organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome

Gabrielle V Rushing et al. Ther Adv Rare Dis. .

Abstract

Okur-Chung neurodevelopmental syndrome (OCNDS) is an ultra-rare disorder caused by variants in the CSNK2A1 gene. CSNK2A1 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 CSNK2A1 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 CSNK2A1 gene, highlight gaps in OCNDS research, discuss the research roadmap, and offer the founder's perspective on our growth and future opportunities.

Keywords: CK2; CSNK2A1; OCNDS; Okur Chung; Roadmap; rare disease.

Plain language summary

Patient organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome Okur-Chung Neurodevelopmental Syndrome (OCNDS) is an ultra-rare disorder caused by variants in the CSNK2A1 gene.CSNK2A1 creates a subunit of CK2, a critical protein in brain development among other biological processes.There are no approved treatments for OCNDS, and current suggested treatments focus on symptom management.Individuals with OCNDS exhibit many symptoms at varying severity levels, including developmental delay/intellectual disabilities, autism, disrupted sleep, speech delays/inability to speak, short stature, and in approximately 25% of cases, epilepsy. We think that seizure prevalence may be underreported due to lack of extended EEG recordings for OCNDS patients and that seizures may preferentially occur at night as has been observed in other autism spectrum disorders.The CSNK2A1 Foundation was established in 2018 and aims to find a cure for OCNDS and provide support to affected individuals. The CSNK2A1 Foundation’s research tools and efforts have provided valuable insights into the biology of OCNDS and the natural history of the disorder. However, additional efforts are needed to fully understand how OCNDS affects the body and investigate potential treatment approaches.To accelerate OCNDS research, the foundation has developed a research roadmap that is presented in this perspective article. We describe OCNDS and the CSNK2A1 gene, highlight gaps in OCNDS research, discuss the research roadmap, and offer the founder’s perspective on our growth and future opportunities.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Symptoms of OCNDS. OCNDS, Okur-Chung neurodevelopmental syndrome.
Figure 2.
Figure 2.
CSNK2A1 Foundation’s research roadmap for OCNDS. OCNDS, Okur-Chung neurodevelopmental syndrome.
Figure 3.
Figure 3.
CSNK2A1 Foundation’s 2024 engagement plans.
Figure 4.
Figure 4.
CSNK2A1 Foundation’s four pillars.
Figure 5.
Figure 5.
Timeline of CSNK2A1 Foundation’s major milestones.
See this image and copyright information in PMC

References

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    1. Okur-Chung Neurodevelopmental Syndrome – GeneReviews® – NCBI Bookshelf, 2022, https://www.ncbi.nlm.nih.gov/books/NBK581083/ (accessed 25 October 2023).
    1. Belnap N, Price-Smith A, Ramsey K, et al.. Inherited CSNK2A1 variants in families with Okur-Chung neurodevelopmental syndrome. Clin Genet 2023; 104: 607–609. - PubMed
    1. Lamb GV, Green RJ, Olorunju S. Tracking epilepsy and autism. Egypt J Neurol Psychiatry Neurosurg 2019; 55: 55.

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