A patient organization perspective: charting the course to a cure for SCN2A-related disorders

Abstract

The SCN2A gene encodes the Nav1.2 protein, a voltage-gated sodium channel crucial for initiating and transmitting action potentials in neurons. Dysfunction in Nav1.2, often stemming from genetic mutations in the SCN2A gene, leads to SCN2A-related disorders. Individuals harboring pathogenic SCN2A variants present with severe neurodevelopmental disorders such as epilepsy, autism spectrum disorders, movement disorders, cortical visual impairment, and intellectual disabilities. The FamilieSCN2A Foundation, a 501(c)(3) patient advocacy organization, is dedicated to enhancing the lives of those affected by SCN2A-related disorders. Fueled by a vision of a world with effective treatments and cures for all patients with SCN2A-related disorders, FamilieSCN2A Foundation has charted the course to a cure based on their core values of urgency, integrity, collaboration, and inclusion. Their strategic plan centers on building a comprehensive research-readiness infrastructure that maximizes the probability of bringing curative therapies to SCN2A patients. Appreciating that statistically most drug development initiatives will fail, creating an infrastructure that maximizes the number of drugs in development for SCN2A-related disorders in turn maximizes the net probability of success that FamilieSCN2A Foundation will achieving their vision. Through dynamic initiatives and notable achievements, including raising ~$6 million USD, funding 26 research grants totaling ~$4.7 million USD, and forging strategic partnerships across the SCN2A-related disorder ecosystem the foundation is actively executing its strategic plan. With SCN2A research advancing rapidly and a thriving ecosystem of diverse, engaged stakeholders, FamilieSCN2A Foundation believes the outlook for SCN2A-related disorders is bright.

Keywords: Nav1.2; SCN2A; autism; epilepsy; roadmap.

Figure 1.

Variations in SCN2A led to a spectrum of clinical phenotypes. Clinical and functional spectrum of SCN2A-related disorders. Purple indicates more gain of function Nav1.2 properties while blue represents more loss of function, and white/normal represents an SCN2A without mutation/dysfunction. Mixed Function Represents Nav1.2 channels that have some LoF and some GoF electrophysiological parameters. Boxes below include common symptom clustering that occurs within each respective zone of the Nav1.2 functional excitability spectrum. ASD, autism spectrum disorder; BFNIS, Benign/self-limited Familial Neonatal Infantile Seizures; DD, developmental delay; GI Dys, gastrointestinal dysfunction; IEE, infantile epileptic encephalopathy; IS, infantile spasms; Sleep Dys, sleep dysfunction.

Figure 2.

Total publications discussing SCN2A or Nav1.2 have increased over time. Graph shows the number of SCN2A publications on PubMed by year. PubMed search query used was “SCN2A OR NAV1.2” and then manually adjudicated to remove irrelevant publications. Current to August 7, 2024.

Figure 3.

The FamilieSCN2A Foundation’s Four Pillars of Research-Readiness Strategy: clinical phenotyping, basic research, translational research, and clinical trial research. Illustration of FamilieSCN2A Foundation’s Four Pillars of Research-Readiness Strategy. Each category described in greater detail in the body of the publication.

Figure 4.

Clinical phenotyping creates a detailed and nuanced understanding of the disorder from a clinical perspective. Diagram of FamilieSCN2A Foundation’s Efforts in Clinical Phenotyping described in greater detail in the publication.

Figure 5.

Funding mechanisms dedicated to SCN2A-related basic research. Illustration of FamilieSCN2A Foundation’s funding mechanisms, each described in greater detail in the publication.

Figure 6.

Depiction of the different forums hosted by the FamilieSCN2A Foundation to facilitate scientific discussions. Illustration of FamilieSCN2A Foundation’s platforms that facilitate scientific discussion, each described in greater detail in the publication.

Figure 7.

The FamilieSCN2A Foundation comprehensive and multifaceted approach to supporting translational research readiness. Illustration of FamilieSCN2A Foundation’s muti-faceted approach to supporting translational science, each described in greater detail in the publication.

Figure 8.

Diagram of criteria that the FamilieSCN2A Foundation addresses attracts industry investment and collaboration. Illustration of elements that FamilieSCN2A Foundation believes make SCN2A an attractive target for drug development, each described in greater detail in the publication.

Figure 9.

Strategic capital deployment and ROI analysis. Capital deployment for the FamilieSCN2A Foundation grants and analysis of some return on investment key performance indicators. Colors investment legend: Blue: Basic science investments; Orange: Young investigator investments; Green: Natural History/Endpoint Assessment; Red: Drug discovery/Development; Purple: Clinical; Brown: Biomarker Discovery.